NANOTECHNOLOGY PLATFORMS AND SECTORAL DIFFUSION PATTERNS IN DRUG,

AND FOOD DELIVERY SYSTEMS

A Historical, Empirical And Theoretical Study Of Technological Convergence Across Previously

Distinct Industries

Hailing Yu

Materials Department

School of Engineering and Materials Science

Queen Mary, University of London

Prepared for THE 5TH INTERNATIONAL PH.D. SCHOOL ON

NATIONAL SYSTEMS OF INNOVATION AND ECONOMIC DEVELOPMENT

GLOBELICS ACADEMY

Tampere, Finland, from 2nd of June to 13th of June 2008

[email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY

Abstract

The fundamental proposition investigated in this paper is that the nanotechnologies developed for each of these different market sectors have the potential to diffuse out of their vertical market across to the other industries. A typical example is in the use of encapsulation such as liposomes, which are already finding applications in the delivery of anti‐cancer drugs, skin nutrients in cosmetics and flavors in the food . The thesis combines an in‐depth understanding of the emerging science base at the nanoscale with an investigation of what the implications might be for the economics of technical change, the process of diffusion of generic platforms and the convergence of previously separate industries and markets. In addition with huge government funding, it is important to understand the pace and nature of this convergence. As such this is a pioneering study in areas, which although little understood at present, are of increasing importance in the economics of innovation, national systems of innovation and public policy within and between knowledge‐based economies.

Key words: Nanotechnology Platform; Delivery Technology; Technology Convergence

Abstract...... 1 List Of Figures...... 2 Introduction...... 2 Background...... 2 Research Questions...... 3 Expected Results And Contribution To The Literature...... 4 Methodological Approach And Analytical Frameworks...... 4 Technological Change and Diffusion ...... 5 General principles to characterize technology...... 6 Technological change from an evolutionary perspective ...... 7 Technology diffusion: the ex-post selection mechanisms in the process of technological change...... 7 The General Purpose Technology concept and nanotechnology platform...... 8 The GPT concept and nanotechnology platform...... 9 Strategies to identify a GPT...... 11 Literature Review ...... 13 Research Question 1: How have the industries of Pharmaceuticals/Drug Delivery, Cosmetics/skin care and Food evolved on their separated paths in the 20th Century? (Characteristics, Commonalities and Differences) ...... 13 Technological change in the pharmaceutical industry...... 13 History of drug delivery...... 14 Novel drug-delivery systems ...... 14 Technological change in cosmetics industry ...... 15 History of Cosmetics ...... 15 Cosmetics/Personal Care Delivery Systems...... 16 Technological change in food industry...... 17 Food science and technology...... 17 The interrelation of food and drugs ...... 18 Controlled release in food delivery...... 18

Hailing Yu Page 1 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY

Research Question 2: How is nanotechnology leading to the creation of generic nanoplatform e.g. nanoplatform-based delivery system? ...... 20 Diffusion of nanotechnology in drug delivery...... 20 Diffusion of nanotechnology in cosmetics/skin care delivery...... 23 Diffusion of nanotechnology in food delivery...... 23 Research Question 3: What will be the impact of the diffusion of nanoplatform-based delivery technologies (1) Pharmaceuticals/drug delivery, Cosmetics/skin care and Food R&D? and, (2) market and technological convergence between previously distinct indutries?...... 24 New Delivery Systems for Nutraceutical (Nutracosmetic) and Cosmeceutical Formulations...... 24 Reference ...... 26 List Of Figures

Figure 1: Controlled release technologies in cosmetics, food and drug delivery...... 3 Figure 2: Application matrix of nanotechnology in food science and technology...... 3 Figure 3 Potential sequence of science, intermediate goods, and final products in nanotechnology...... 11 Figure 4 History of drug discovery...... 13 Figure 5 Physical and chemical types of controlled release systems ...... 19

List of Tables

Table 1: Classification of DDSs based on drug-release mechanism and technology...... 15 Table 2 Common rationale required for the development of a delivery system ...... 17 Table 3 Examples of drug delivery technologies in relation to the current nanotechnology revolution...... 20 Table 4 Examples of nanotechnologies ...... 21 Table 5 Examples of nanotechnologies for drug delivery...... 22 Table 6 Popular nutracosmetic ingredients...... 25

Introduction

Background

An initial investigation into the development and the use of nanotechnology‐enabled delivery technologies in Personal Care, Food and Pharmaceutical industries, indicated that numerous opportunities for technology transfer exist at the interface between the Pharmaceutical (i.e., Drugs), Personal Care (i.e., Cosmeceuticals & Functional Actives), and Food (i.e., Nutraceuticals) industries. Some of the forces associated with the industry’s recognition of the need to move to a higher ground include providing protection of functional actives from processing, environmental, and formulation stressors. Fortunately, these needs are timely since they correspond with the emergence of a Technology Platform to provide solutions for these issues (i.e., Delivery Systems). This science relies upon a whole range of new and existing technologies. These technologies are evolving at a rapid rate and address the need for novel approaches to carry actives within formulations and successfully deliver them to substrates like skin and hair. These methodologies provide technology that controls when the actives should be delivered, where they should be delivered, how they should be delivered,

Hailing Yu Page 2 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY and enable their delivery at an optimal rate. There is much of interest to those individuals responsible for research, marketing, and business in these other markets.

Figure 1: Controlled release technologies in cosmetics, food and drug delivery

Figure 2: Application matrix of nanotechnology in food science and technology

Hence there are both technology push factors and market pull factors making for the development and diffusion of advanced nanotechnology platforms within and between adjacent industries. A key aspect of my research is to examine and quantify precisely how nanotechnology makes possible diffusion, integration and convergence patterns that were not possible before. In the past generic or general purpose technologies such as the electric motor diffused across diverse industries from mining to manufacturing to consumer goods. What is different with technology platforms at the nanoscale?

Research Questions

Hailing Yu Page 3 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY

The research questions have been re‐examined and polished several times and evolved in the following ways: • Research Question 1: How have the industries of Pharmaceuticals, Cosmetics and Food evolved on their separated paths in the 20th Century? (Characteristics, Commonalities and Differences) • Research Question 2: How is nanotechnology leading to the creation of generic “Nanoplatforms”? • Research Question 3: What might be the impact of the diffusion of nanoplatform‐based delivery technologies on (1) Pharmaceuticals, Cosmetics and Food R&D? Will their core technology and organizational competences converge? and, (2) Market and technological convergence between these previously distinct industries?

Expected Results And Contribution To The Literature

Following on from above, the thesis examines the impact of these nanoplatform delivery technologies on company level R&D, core competence acquisition, diffusion patterns, inter‐industry competition, and the blurring of market boundaries. More specifically the thesis will provide analytical frameworks and data, which address the following sets of issues:

R&D and the Building of Nanotechnology Platforms • Building nanotechnology delivery platform for drug delivery; • Building nanotechnology delivery platform for cosmetics delivery; • Building nanotechnology delivery platform for food delivery.

Strategic R&D Management and Competition • How can companies strategically manage R&D on delivery technologies platforms to enter adjacent industries and markets? • How do companies build nanoencapsulation platforms? • How are nanoplatforms related to core competences? • How can companies deepen/protect nanoplatform competences? (Role of patents, Protect, block or bargain?) • What is impact of nanoplatfoms on competition/entering new markets? Methodological Approach And Analytical Frameworks

By its very nature, the research into the three questions posed above necessarily relies on secondary data and qualitative analysis in order to examine the historical trends and characteristics in the selected industries under investigation. Similarly, the trends and characteristics in the nanoscience, nanotechology and nanobiotechnology foundations of the research also rely on secondary and qualitative data, information and analysis. However, these data are supplemented by case studies and interviews providing primary information in the last chapter of the research.

In order to address the 1st Research Question, I examine in detail the evolution of the three industries in the 20th century, drawing out the distinct differences in terms of science and technology base, their commonalities and market drivers. This is done in the context of a literature review of the process of technological change and diffusion, the role of the firm in technological change from an evolutionary and knowledge‐based view in order to ground our analysis in firm theoretical foundations. Here the Hailing Yu Page 4 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY three industries are looked at from the point of view of the economics of technical change evolutionary, demand driven or technology driven or all three together (Ruttan 2001, Kaounides, Yu and Harper 2007). This then enables us to incorporate the arrival of nanotechnology in the science and technology base of the industries, its diffusion, and to investigate whether technical change in these industries is indeed becoming nanotechnology based, indeed nanoplatform technology based within all three and drawing them ever closer together in techniques, applications and markets.

For answering the 2nd Research Question, the thesis focuses on an in‐depth understanding of the arrival of nanoscience and nanotechnology, the convergence of the physical and life sciences, and the cross fertilization in and techniques. This is then related in depth to the three case study industries. This leads us naturally to the concept of nanotechnology platforms and whether these somehow act as generic technologies or general purpose technologies and might be the economic consequences of this on R&D, core competence acquisition and the blurring of industry boundaries. Thus the thesis attempts to make a contribution on some deep‐seated questions in the literature while addressing issues of major and current policy significance. What is the connection between a General Purpose Technology and a nanotechnology platform?

Attention has increasingly shifted towards the long‐run perspective on technological innovation, which suggests that progress comes in waves, each one originating with a major breakthrough or general purpose technology (GPT) (Jovanovic, J., & Rousseau, P. 2005). This paper seeks to assess whether nanotechnology is likely to be (or become) a GPT, a characteristic that other researchers have sometimes assumed though not necessarily documented. Based on a survey of existing literature, this paper will explore the extent to which nanotechnology addresses three primary characteristics of a GPT: pervasiveness, innovation spawning, and scope for improvement. The paper draws on patent and patent citation databases to highlight the types of quantitative and qualitative information that would be necessary, and in some instances is still lacking, to characterize fully the nature of nanotechnology and the building of generic platforms at the nanoscale. In order to achieve its objectives the thesis focuses on Delivery Systems.

Following on from the answers, data and insights form RQ1 and RQ2, the thesis brings together the secondary and primary data in order to provide new and original answers to the question as to whether nanoplatform delivery technologies in food, cosmetics and drug delivery constitute General Purpose Technologies.

Technological Change and Diffusion

The idea of evolutionary technological change comes largely, on the one side, from historical and sociological research traditions and, on the other side, from evolutionary economics (Nelson, Nelson 2002, p. 265; McKelvey 1996, p. 36).

• How does technological change in the industry occur? • Which are the mechanisms shaping the relative importance of technologies and their development paths? • How do firms contribute to these processes? • How do firms react when new technologies emerge outperforming the technologies they master? Hailing Yu Page 5 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY

This research attempts to understand these processes guided by evolutionary theory. Dosi and Nelson (1994, p. 154) use the term “evolutionary” to define theories, models or arguments. There are several reasons why consider the evolutionary framework as appropriate to explore technological change.

Firstly, it provides comprehensive theoretical explanations suggesting that the aggregate pattern of technological change at the industry level draws on mechanisms at lower levels of aggregation such as the level of the firm. Additionally, it provides the conceptual tools to explore technological change as a process relying on the accumulation and transmission of knowledge, skills, and behaviour among the actors involved. Moreover, the evolutionary approach to explore technological change admits its historical conditioning. Hence, from an evolutionary perspective historical reconstruction needs to be merged with the analysis of the process of technological change. The acknowledgement of history dependent processes of technological change at an aggregate level (such as the level of the industry or the economy) does not necessarily imply the need of the historical characterisation of micro behaviours. History dependence at the system level can be the outcome of an invariant choice process subject to some sorts of externality, dynamic increasing returns, multiple locally stable equilibria etc. However, the analysis of technological change can very much profit from the historical‐ characterisation of micro behaviours. Which technologies emerge and how they develop and diffuse cannot generally be considered independently from the particular sequence of actions of their developers and adopters (Dosi et al. 1992, p. 4.)

General principles to characterize technology

A key step towards the characterisation of technology is the recognition of its imposed function, which determines how technology should behave or the task it should accomplish. Therefore, technology involves a transformation of the world in order to reach a predefined behaviour (Nightingale 1998, 2004).

Metcalfe puts forward a dualistic approach to technology according to which technologies have two dimensions: the artefact dimension and the knowledge dimension (Metcalfe, Boden 1992).

The artefact dimension refers to the physical devices articulating the transformation process of inputs into outputs. Moreover, it embodies the physical achievements in the development of a technology, which can be captured in terms of performance of outputs (for instance functional or qualitative performance) or of production processes applied (in terms of necessary equipment and its costs or environmental criteria, for example).

On the other side, technology as knowledge refers to the concepts, theories and practices underlying the transformation process and the actions that enable its operation. Technology involves different types of knowledge such as tacit knowledge (which can not be easily articulated and communicated) and codified knowledge (which can be expressed in symbolic form and easily articulated). Nelson and Winter (1982) suggest that real life knowledge can often be placed on a continuum between perfectly codified and tacit knowledge. Moreover, the nature of knowledge in terms of degree of "codifiability" may change overtime (Saviotti, Metcalfe 1991).

An important issue in innovation studies and in science and technology policy is the interaction Hailing Yu Page 6 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY between technology and science. To explore this interaction it is necessary to understand the differences between science and technology.

Given these considerations, and taking into account that technological change is the result of interactions among individuals, populations and environments over time, the following section discusses the process of technological change from an evolutionary perspective.

Technological change from an evolutionary perspective

Traditionally the so called "technology push" and "demand pull" theories have attempted to explain the drivers and patterns of technological change by focusing either on the supply factors shaping new technological opportunities to be exploited (such as scientific development) or, alternatively, on the needs of users and beneficiaries of technology as main drivers of technological activities. Dosi (1982) points out that both approaches have different understandings of the role of market signals in the process of technology development and, moreover, they fail to provide a theoretical framework for technological change.

On the one hand, the demand‐pull approach implies a‐priory recognition of the needs of technology users (Mowery, Rosenberg 1979). This assumption contradicts the uncertain nature of technology discussed above. Even if technology developers were able to identify a priori the needs of technology users, the range of products or processes satisficing their needs may be unknown. Even in the best case ‐ that is, if these artifacts were known ‐ the scientific and socio‐economic environment might set strong constraints to develop them. Technological solutions are not readily available (Rosenberg 1976, p. 63). In other words, market signals alone are not able to drive technology development.

On the other hand, the technology‐push approach is not reconcilable with the obvious fact that socio‐ economic factors (and not technological and scientific conditions exclusively) are important in shaping the direction of the innovation process. Users of technology, for instance, have a strong influence on the path of technological change.

To conciliate the independence of technology development from socio‐economic mechanisms (suggested by the technology push approach) and their relevance shaping technological change (suggested by the demand‐pull approach), evolutionary economists point out that technological change does not happen at once; it is rather a gradual process. Tentative models aiming at explaining this process should consider that technological change involves firstly the emergence of possible technological solutions (in other words, the generation of variety or the establishment of a set of alternative technological solutions to solve a problem). This process is followed by further selection procedures in a socio‐economic context that limit the set of alternative solutions, determine their relative importance over time and the direction of technological development.

Technology diffusion: the ex‐post selection mechanisms in the process of technological change

At a certain point, when the set of alternative technological solutions is better known by the institutions involved, the solutions undergo a monitoring process that determines their relative importance and the pattern of technological changed observed. Thus selection environments frame Hailing Yu Page 7 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY the processes of competition and technological accumulation, determining the technological improvements that become innovations and their relative importance over time.

According to the path dependence perspective, once a technology is somewhat ahead of the others in the selection environment, a variety of factors will reinforce the development of this technology. Moreover, this relative importance of a technology over the alternatives can become stable since these factors can influence the choice for one technology in future periods. If this occurs, the process is said to be path dependent. Arthur (1988) identifies the following sources of path dependence: • Learning by using; • Network externalities; • Scale economies in production; • Informational increasing returns; and • Technological interrelatedness.

To sum up, after the set of possible technological solutions is known it undergoes a monitoring process based on the definition of worth or merit determined by the selection environment where firms compete to seize innovation opportunities. The monitoring process selects which technological solution develops further and diffuses. However, this endogenous competition of technologies and problem solving methods in the selection environment is influenced by network externalities and forms of dynamic increasing returns. For instance, the development of particular technologies and the development of specific problem solving‐methods increase the capabilities of firms in these specific directions, increasing the incentives to do so in the future. Experience and incentives of firms in the selection environment are hence important factors determining technological change. The same holds for the existence of complementary technologies or standards. These elements may prevent firms to deviate from established technological solutions and from experimenting along alternative technological trajectories.

The General Purpose Technology concept and nanotechnology platform

Attention has increasingly shifted towards the long‐run perspective on technological innovation, which suggests that progress comes in waves, each one originating with a major breakthrough or general purpose technology (GPT). This research seeks to assess whether nanotechnology is likely to be a GPT, a characteristic that other researchers have sometimes assumed though not necessarily documented. Based on a survey of existing literature, this research will explore the extent to which nanotechnology addresses three primary characteristics of a GPT: pervasiveness, innovation spawning, and scope for improvement. The research draws on patent and patent citation databases to highlight the types of quantitative and qualitative information that would be necessary, and in some instances is still lacking, to characterize fully the nature of nanotechnology.

Whenever a new class of technologies emerges, conjectures are advanced on how likely it is that they will change firms’ productivity, household production, consumption patterns, and socio‐economic relationships. If a core technology has a substantial and pervasive effect across the whole of society, it is often termed a ‘‘General Purpose Technology’’ (GPT). The dissemination of electricity at the turn of the 19th century is often said to have the character of a GPT, with reference made to the long wave of downstream innovations spawned by the electric dynamo that reshaped the functioning of the economy. Similarly, the dissemination of microelectronics in the last quarter of the 20th century has in Hailing Yu Page 8 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY it the hallmarks of a GPT in that it led to new forms of organizations, new products, and has increased the level of competition in service goods that were traditionally produced and consumed locally.

The question explored in this section is whether nanotechnology platform has the potential of inducing changes in the economy that are comparable in scope to electricity, information and communications technology (ICT), and others that have been previously documented as major breakthroughs.

The question is discussed by drawing on techniques and ideas from two interrelated streams of research. One line of research has hypothesized that the long‐run behavior of the financial market and of macro aggregates are best understood by investigating the conditions that have favored the arrival and the process of dissemination of major technologies. The main idea from this literature is that technological change follows a sequence of events in which a major technological innovation is preceded by a number of smaller inventions that expand the range of applicability of the core technology, the so‐called ‘‘General Purpose Technology.’’ This research briefly summarize the main features an innovation should have to be part of the club of GPTs and discuss the prediction of theories that explain the rise and fall of productivity and of firms’ value as the outcome of the dissemination of a GPT.

The research draws from a stream of research that describes and characterizes technological developments by means of quantitative data taken from patent datasets. In particular, A comparison was proposed that the level of ‘‘generality’’ of nanotechnologies relative of that of ICT (usually considered a GPT) and innovations in the drug industry (not considered a GPT). The kind of tests proposed in the literature are not easily applicable to emerging technologies because these tests have been devised for situations in which a considerable amount of historical data has been recorded. Nevertheless, the estimations that were performed seem to suggest that nanotechnology satisfies at least one major of a GPT, namely that of generality.

The GPT concept and nanotechnology platform

Previous research has suggested that a GPT must have at least three attributes: pervasiveness, an innovation spawning effect, and scope for improvement (Helpman & Trajtenberg, 1994). Pervasiveness is intended to reflect the performance of some function that is vital to the functioning of a large segment of existing or potential products and production systems. Bresnahan and Trajtenberg (1995, p.4) argue that ‘‘continuous rotary motion’’ and ‘‘binary logic’’ are the pervasive elements of ‘‘steam power’’ and ICT, respectively, each of which is considered a GPT.

A pervasive technology would have relatively little visibility in the functioning of the economy unless it fostered new inventions that directly or indirectly result from the early major invention. For instance, the dynamo led to the invention of both the light bulb and electric motor, and stimulated major innovation in plant and urban design (David, 1990). Similarly, the microchip led to an explosion of imaging technologies, memory devices, and digital technologies.

Helpman and Trajtenberg (1994) suggest that such widespread adoption of a core technology is a consequence of a variety of actors coordinating their beliefs about the promise of the technology. Complementary technologies are developed as long as the various actors involved share beliefs that Hailing Yu Page 9 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY the GPT is spawning innovations in multiple technological areas. Indeed, widespread market adoption may be a consequence of the settling of beliefs among scientists, entrepreneurs, established businesses, government, and consumers.

It remains a theoretical and empirical question whether the core technology of these ‘‘breakthroughs’’ could be improved substantially. Evidence for the scope of improvement for ICT was cleverly summarized by ‘‘Moore’s Law’’, which predicted that the force of competition would stimulate the semiconductor industry to double the number of transistors per chip every 18–24 months. While the regularity of ‘‘Moore’s Law’’ has been observed, it is not clear whether its regularity results from technological factors or from industry coordination around a smooth and predicable trajectory with clear transaction‐cost benefits.

Theory suggests that all three aspects will be present in the true breakthrough technologies, those most widely used by firms and households. The mere fact that an innovation can be applied in several areas of production (pervasiveness) does not mean that it will be used. In order for society to employ the technology pervasively, its adoption must be convenient from a cost‐consideration point of view, that is, it must reach a certain level of efficiency (scope for improvement), and it must lead to the development of new ‘‘secondary’’ or ‘‘complementary’’ technologies (innovation spawning). Some authors add a fourth element to the definition of a GPT, that of wide dissemination (Lipsey, Bekar, & Carlaw, 1998), although this element is often considered a logical consequence of the other three attributes.

Are there indications that these three basic GPT attributes might be present in nanotechnology? Can we say that nanotechnology performs a generic function, whose efficiency will be greatly improved over time, perhaps as much as that of the microprocessor, and that it stimulates the appearance of new kinds equipment comparable to the modem, or memory storage devices?

With a new technology it is hard to conjecture what aspect of it, if any, will perform a generic function. Although most scholars who are engaged in nanoscience agree that nanotechnology is very small in scale, (in the range of 1–100 nanometers (nm), with one nanometer equaling one billionth of a meter), only a few seem to embrace the notion that if a technology is small in scale it should be considered nanotechnology. From the perspective of this analysis such a change in scale could be paralleled to a generic function, notwithstanding the disagreements among nano‐scientists. This would be the case, for instance, if a new scientific principle or a new methodology allows a significant drop in scale that leads to a radical transformation in the range of inputs used in production.

Figure 3 presents a schematic, sequencing both science and commercial technologies. The sequence begins with scientific and technological discoveries in instruments (such as scanning tunneling microscopes or STM and atomic force microscopes or AFM) and nanomaterials (such as buckminsterfullerenes and carbon nanotubes), forming the basis for a value chain. Intermediate and complementarygoods producers are offered, including nanocoatings and composites manufacturers, nano‐core processing and memory. The end of the value chain shows a broad range of end‐use goods. The figure shows that the boundaries between positions in the value chain overlap.

It is fair to assume that the development of a complete value chain will more likely follow a coordination of beliefs. In nanotechnology, this coordination of beliefs appears to be taking hold. Evidence of coordination in science includes Richard Feynman’s legendary talk at the American Hailing Yu Page 10 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY

Physical Society’s annual meeting in December 1959 (‘‘There’s Plenty of Room at the Bottom’’), Eric Drexler’s Engines of Creation (1986) and subsequent formation of The Foresight Institute, the launch of Nanotechnology by the Institute of Physics as a multidisciplinary science and engineering journal in 1990, the creation of the Feynman Prize first awarded in 1993 to recognize eminent research in nanotechnology, and the notion that advances at the nanoscale are situated in a convergence of disciplines (Roco & Bainbridge, 2003).

Figure 3 Potential sequence of science, intermediate goods, and final products in nanotechnology

Armed with such information, several researchers have proposed that nanotechnology is a GPT. Huang et al. (2003) demonstrate through patent analysis that nanotechnology covers a wide range of classes, although Porter, Shapira, and Youtie (2006) criticize the use of an overly broad definition. Moreover, Shea (2005) suggests that nanotechnology is a GPT because it is likely a disruptive and radical technology, but the author’s approach does not specifically address the concepts of pervasiveness, innovation spawning, and scope for improvement. While Palmberg and Nikulainen (2006) do examine whether nanotechnology exhibits these three characteristics of a GPT, they do not apply methods commonly used to test for them.

Counting the number of patents by year (showing increases over time) or patents by patent classification (showing increasing diversity) are commonly used to claim that nanotechnology is a GPT. However, such information may not in and of itself be adequate to make any such determination. Hall and Trajtenberg (2004), for instance, find that GPT’s (as measured by patent citations) do not necessarily have disproportionately higher growth rates in terms of newly issued patents. Moreover, they argue that some patent classifications tend to be more broad‐based than others, particularly chemical‐related classifications. They suggest that patent classes by themselves do not provide sufficient substantiation of breadth and pervasiveness of a candidate GPT.

Strategies to identify a GPT

We (1) suggest that identifying whether a technology is a GPT is a valuable exercise, and (2) cataloged

Hailing Yu Page 11 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY other studies finding that nanotechnology exhibits the characteristics of a GPT. In this section, we identify what we believe is a more systematic approach, one that has been undertaken in recent years by empirical scholars and economic historians in assessing whether a technology is a GPT, and apply it to nanotechnology. The objective of this discussion is to both examine whether nanotechnology ‘‘holds up’’ as a GPT, and also to identify tools that may be used to test other emerging technologies.

A technology will spawn complementary innovations by using patent analysis. It relies on a notion that patents presage investment in new technologies, representing the rise in initial public offerings (IPOs) and the subsequent change in the structure of capital in favor of new technologies.

Hall and Trajtenberg (2004) and Moser and Nicholas (2004) venture beyond a simple tally of the number of patents to contend that the data can reveal much more on the question of whether a technological development is a GPT. Instead of measuring the pervasiveness of a GPT by looking at how a new technology affects the composition of capital across sectors, these authors look at the extent to which patents associated with a GPT are cited outside the technology area or industry in which the GPT originated. To address the diffusion delay, which has been associated with a prolonged productivity slowdown followed by an acceleration of productivity, this literature measures the citation lags (the amount of time between the issue of a focal patent and the issue of a future patent that cites back to it), which they contend should be longer for GPTs than for incremental technologies. These authors measure the ‘‘scope for improvement’’ not as a reduction in production cost, but instead with the number of citations within the technological area to which the GPT belongs. An interesting question that the patent literature addresses is the date of arrival of a GPT. Historians often pick a specific event, usually identified with a major investment (e.g., for electricity it has been identified as the construction of a hydro‐electric facility at Niagara Falls, New York). Macroeconomists tend to consider an arbitrary threshold in the data, for instance investments in the new technologies rising above a certain percentage of overall investment.

Does the patent approach lead to the same conclusions as the macro approach? Moser and Nicholas contend that in the case of electricity it does not. These authors find that patented inventions associated with electricity filed in the 1920s were not as ‘‘pervasive’’ as were chemical and mechanical inventions, because these latter inventions were cited by later patents outside their technological areas more often than were electricity inventions. Moreover, chemical and mechanical inventions were cited more often in general, indicating to the authors a stronger propensity to spur innovation.

These differing conclusions may stem from chemicals and mechanical industries being more ‘‘science‐ based’’ than was electricity. This observation is an important warning for all nanotechnology investigations that rely exclusively on patents data. There is a risk that the traditional test developed by Hall and Trajtenberg (2004) may be biased in the sense that a science‐based technology is more likely to be designated as a GPT, even when such a determination is a spurious result, and not borne out by a judgment made after considering the economic effects that it actually generates.

Hailing Yu Page 12 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY

Literature Review

Research Question 1: How have the industries of Pharmaceuticals/Drug Delivery, Cosmetics/skin care and Food evolved on their separated paths in the 20th Century? (Characteristics, Commonalities and Differences)

Technological change in the pharmaceutical industry

Figure 4 History of drug discovery

In simple words the pharmaceutical industry links activities and business accomplishing the discovery, development, production and commercialisation of drugs (i.e. products with therapeutic properties). Accordingly, product innovation is based on the search and development of molecules that may have desirable therapeutic effects. Basically new drugs can be developed either with the application of organic chemical synthesis or from the separation of compounds produced by natural microorganisms, which as an application of biotechnology. The development of these technologies (chemical synthesis and biotechnology) during 19th and 20th centuries has tremendously changed the conditions for innovation in the pharmaceutical industry. An interesting aspect of the pharmaceutical industry is the interaction between science and technology. Scientific advances have contributed to the development of the knowledge base underlying drug discovery and development. Indeed, the pharmaceutical industry can be considered an extreme case of a science‐based industry (Gambardella 1995).

During the establishment of the modern pharmaceutical industry in the last decades of the 19th century, the scientific principles of organic chemistry guided drug discovery without providing understanding about the biological processes of diseases. However, this constraint did not prevent drug producers from developing promising drugs by synthesising compounds, which could be tested

Hailing Yu Page 13 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY for therapeutic properties using animal models.

In contrast, after a period of successful application at the beginning of the 20th century, biotechnology for drug production remained more or less a niche technology in pharmaceuticals until the 1960s. Scientific advances in molecular biology and biochemistry provided drug discovery with scientific knowledge on protein structure and on the function of proteins. To describe the contributions of biochemistry and of molecular biology in pharmaceuticals scholars refer to a transition from a chemical/random screening to a biological drug design model (Gambardella 1995; Henderson et al. 1999). Moreover, after the 1970s, with the discoveries of recombinant DNA (rDNA) and monoclonal antibodies, biotechnology became a key for drug discovery and development and production.

History of drug delivery

Drug delivery has metamorphosed from the concept of a pill to molecular medicine in the past 100 years. Better appreciation and integration of pharmacokinetic and pharmacodynamic principles in design of drug delivery systems has led to improved therapeutic efficacy. A greater understanding of the molecular transport in relation to physico‐chemical properties has led to the evolution of a biopharmaceutics classification system, which should be a future road map, governing drug design, development and delivery. While drugs belonging to class I and II will be delivered by established platform technologies, novel delivery strategies will evolve and mature to realize the potential of ‘new generation’ biotech and non biotech drugs belonging to class III and IV, respectively. Nanotechnology involved drug delivery belongs to this category.

Drug research has evolved and matured through several phases beginning with the botanical phase of the early civilizations, through to the synthetic chemistry age in the middle of the 20th century, and finally the biotechnology era at the dawn of the 21st century. Since the formation of the pioneering companies in this area, Alza Corporation (USA) and Elan Corporation (Ireland), in the 1960s, more than 350 drug‐delivery and 1000 medical‐device companies have come into existence with world‐wide drug‐delivery sales of US$ 22 billion. At the present rate of growth, the drug delivery market comprises 20% of the total pharmaceutical market by 2005.

Novel drug­delivery systems

NDDSs evolved over a period of time to improve patient compliance and optimize the dosage regimen without compromising the therapeutic efficacy. The foundations were laid in 1952, with the introduction of the first sustained‐release capsule of Dexedrine. Subsequently, several concepts originated, including prolonged, timed and extended release and finally matured to controlled release systems. NDDSs can be classified on the basis of their sophistication and mechanism of drug release, as shown in Table 1.

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*CDDS, controlled drug­delivery system. Table 1: Classification of DDSs based on drug-release mechanism and technology

Technological change in cosmetics industry

History of Cosmetics

The first archeological evidence of cosmetics can back to the Egyptians at 4000 BC. It seems affluent women applied a bright green paste of copper minerals to their to provide color and definition of features. They used perfumed oils and painted on themselves with cream made from sheep’s fat, lead and soot.

Origins of Personal Care: When Medicine and Cosmetics Were One. Delivery systems exist in nature and in human technology that mimics nature. It should not be surprising, therefore, to find such systems in “natural remedies” from many sources. The belief that personal care/cosmetics is an undertaking separate from health care (medicine) has not been widely held in human cultures. In some ancient traditions, documented but no longer practiced, perfumery and medicine were both seen as divinely given and were both regulated as sacred activities. In some currently practiced traditions with ancient roots, health practices depend on maintaining beauty and harmony among many internal and external elements. In these traditions, not only body and mind must be kept in balance, but relations between the person and the environment must also be harmonized. In more

Hailing Yu Page 15 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY recently established Western, and especially American, practices, treatment of disease is seen as necessarily separate from the creation of personal or environmental beauty; however, current trends toward educating new physicians in the basics of “alternative medicine,” as well as the growing interest among personal care practitioners and consumers in “functional cosmetics,” suggest that this sense of separation is weakening.

Cosmeceuticals. Although practitioners of Western allopathic medicine must operate in an environment in which “personal care” and “health care” are legally separated, they must also treat a growing population of consumers who are knowledgeable participants in more holistic traditions. The strict definition of medicine becomes blurred under such circumstances. Recent studies of practitioners and students show increasing interaction between practitioners of Western and complementary or alternative medicine, growing consumer expectation that nurses and pharmacists can make recommendations reconciling multiple traditions, and frequent consumer attempts to combine, appropriately or not therapies from traditional and biomedical sources.

Cosmetics/Personal Care Delivery Systems

Recent technological progress has drawn attention to the usefulness of delivery systems in both medical and cosmetic formulations. However, delivery systems are not a new idea. The basic technology used to create modern personal care products is very old. Ancient texts and archeological finds demonstrate that not much has changed. Many of the ingredients, procedures, and final products remain highly recognizable, as shown in examination of ancient emulsification, extraction, and downsizing practices that strongly resemble current delivery systems technologies.

To the cosmetic formulators, a delivery system is the method of delivering active payloads onto the skin, then having them pass through the lipid barrier and, finally, reaching the targeted lower layers beneath. The key to successful delivery of the active and creation of the “perfect product” is to determine what type delivery system is required, if any, for that active.

Delivery systems, which include carriers and vehicles, have received serious attention in the transdermal drug delivery literature since their influence can greatly impact the absorption process. The delivery system contains not only the active drug but also contains other formulation components such as penetration enhancers, stabilizers, and preservatives. All of these functional molecules are necessary for achieving successful drug or personal care active delivery. The physical form of the delivery system/carrier/vehicle is crucial to the absorption process. Forms of these systems range from very small nanosize particles or dispersions to emulsions of both the o/w type and w/o type, as well as lipid lamellar gels and the many other variations.

Delivery systems are designed chemical entities that carry a chosen active compound and allow its approach to its site of action. They can be used to overcome many of the limitations of certain raw materials. For example, by encapsulating an active compound that tends to interact with other ingredients, the formulating scientist can create a physical separation between the components. This separation minimizes or eliminates the undesired interaction. The definition of “delivery systems” is quite broad and includes the carrier formulations, (i.e., the gel, emulsion, suspension, etc.) as well as particulate or molecular carriers (Table 2)

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Table 2 Common rationale required for the development of a delivery system

The search for new solutions to formulate more effective or therapeutic products is not just about finding new ingredients. It is also about finding better methods of administering these actives, and maintaining their bioavailability prior to and following delivery to the specified target. While there are endless possibilities and needs for new delivery systems in the area of drugs, and many of these concepts are being applied to personal care delivery.

Technological change in food industry

Food science and technology

Food science is the scientific understanding of the composition of food under various conditions. This seemingly straightforward definition, however, hides a complex multidisciplinary subject involving a combination of sciences and a knowledge of the composition of food materials and their physical, biological and biochemical behaviour including: • Interaction of food components with each other and/or with other elements or materials Nutrition • Sensory properties • enzymology • Microbiology • Pharmacology and toxicology and • The effects of manufacturing, processing and storage • New areas of research, e.g. nutrigenomics, metabolomics, proteomics and nanoscale sciences

Food technology is the application of food science to the processing of food materials into safe, wholesome, nutritious, tasty and attractive food products. Food technology draws upon and integrates the application of other technologies to food, such as packaging, materials science, engineering, instrumentation, electronics, agriculture and biotechnology.

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The interrelation of food and drugs

Though their historical patterns of growth and development have differed, food and drugs and the industries that produce them have long been closely associated. Standards of quality and safety for foods and drugs are customarily administered by the same regulatory agency, the US Food and Drug Administration being typical. Modern food and pharmaceutical processors employ similar technologies and methods of product and process control.

Among the earliest historical records (ca 2900 BC), the Chinese proclaimed a close association of foods with medicines, both being essential to good health, both derived from plant and animal sources. The Chinese believe many ailments can be cured by diet. They were the first to add burnt sponge, an aquatic source of iodine, for people suffering from goitre.

Oriental beliefs in therapeutic foods is attracting North Americans, one‐third of whom are said to buy herbal remedies as alternatives to prescription drugs. Americans' search for nutritional Elixir vitae has been evident for over half a century. During the 1950s vitamin supplements were in fashion; during the 1960s proteins and amino acids were in favour; in the 1970s extensive publicity was given to essential fatty acids and cholesterol in relation to cardiovascular disfunctions; during the 1980s dietary fibre was of paramount interest. At present the fashion is with ‘functional foods’ and ‘nutraceuticals’, foods believed to possess beneficial pharmacological properties.

Controlled release in food delivery

The method of microencapsulation, among others, can be applied to achieve controlled release in foods. Some of the release mechanisms employed in the food industry involve one or a combination of the following stimuli: a change in temperature, moisture or pH; the application of pressure or shear; and the addition of surfactants. Encapsulation is a method of protecting food ingredients that are sensitive to temperature, moisture, microorganisms or other components of the food system. Such food ingredients include flavors, sweeteners, enzymes, food preservatives and antioxidants, and are encapsulated using carbohydrates, gums, lipids and/or proteins. With a properly designed controlled release delivery system, the food ingredient is released at the desired site and time at a desired rate.

Food ingredients may be of natural origin or chemically prepared. In some cases, the natural ingredients can be less potent than the chemical counterparts. On the other hand, the permitted levels of chemical ingredients are low. In either case, it may be difficult to achieve the desired effect without adding high levels of the ingredient. Controlled release is a novel technology that can be used to increase the effectiveness of many ingredients. The performance of natural ingredients can be improved, thereby offering viable alternatives to the less acceptable chemical additives. The technology of controlled release, with its initial roots in the drug industry, has spread to other areas such as the agrochemicals, fertilizers, veterinary drugs, cosmetics and food industries.

The additive present in the microcapsule is released under the influence of a specific stimulus at a specified stage. For example, flavors and nutrients may be released upon consumption, whereas sweeteners that are susceptible to heat may be released towards the end of baking, thus preventing undesirable caramelization in the baked product. Also, carbon dioxide is released when an acid reacts with sodium carbonate during baking. Thus, controlled release delivery systems may be categorized according to whether they involve physical or chemical methods of release of the active agent. Some of Hailing Yu Page 18 30/04/2008 [email protected] Prepared for the 5th International PH.D. SCHOOL GLOBELICS ACADEMY the physically and/or chemically controlled delivery systems that are available are presented in Figure 5.

Figure 5 Physical and chemical types of controlled release systems

The most commonly used method to achieve controlled release in the food industry is microencapsulation. Microencapsulation is defined as the technology of packaging solid, liquid or gaseous materials in miniature sealed capsules that release their contents at controlled rates under the influence of certain stimuli. The shape and size of the microcapsule depend on the shape of the food‐additive material. The simplest microcapsule may consist of a core surrounded by a wall or barrier of uniform or non‐uniform thickness. The core may be composed of just one or several different types of ingredients, and the wall may be single or multi‐layered.

The food industry is taking advantage of the technology of controlled release for food additives including flavoring agents (flavor oils, spices, seasonings), sweeteners, colors, nutrients (vitamins, amino acids, minerals), essential oils, acids, salts, bases, antioxidants, antimicrobial agents, preservatives, ingredients with undesirable flavor and crosslinking agents. Controlled release helps to overcome both the ineffective utilization and the loss of food additives during the processing steps. The release of an active agent may be based on one or a combination of release mechanismsr; these can be time, specific, site specific, rate specific and/or stimulus specific.

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Research Question 2: How is nanotechnology leading to the creation of generic nanoplatform e.g. nanoplatform‐based delivery system?

Diffusion of nanotechnology in drug delivery

Many of the current “nano” drug delivery systems are remnants of conventional drug delivery systems that happen to be in the nanometer range, such as liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals. Liposomes and polymer micelles were first prepared in 1960's, and nanoparticles and dendrimers in 1970's. Colloidal gold particles in nanometer sizes were first prepared by Michael Faraday more than 150 years ago, but were never referred to or associated with nanoparticles or nanotechnology until recently. About three decades ago, colloidal gold particles were conjugated with antibody for target specific staining, known as immunogold staining. To appreciate the true meaning of nanotechnology in drug delivery, it is beneficial to classify drug delivery systems based on the time period representing before and after the nanotechnology revolution.

As shown in Table 3, the drug delivery technologies in relation to the current nanotechnology revolution can be classified into three categories: before nanotechnology revolution (past); current transition period (present); and mature nanotechnology (future). The examples of drug delivery systems of the past (prior to the current nanotechnology revolution) are liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals, as mentioned above. The current drug delivery systems include microchips, micro needle‐based transdermal therapeutic systems, layer‐by‐layer assembled systems, and various micro particles produced by ink‐jet technology. These efforts are just beginning and many fabrication methods have been developed. The future of drug delivery systems, as far as nanotechnology is concerned, is to develop nano/micro manufacturing processes that can churn out nano/micro drug delivery systems.

Table 3 Examples of drug delivery technologies in relation to the current nanotechnology revolution

Examples of the types of nanotechnologies utilized to address the areas listed above can be seen in Table 4. Examples of specific nanotechnologies showing their main applications are provided in Table 5.

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Table 4 Examples of nanotechnologies

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Table 5 Examples of nanotechnologies for drug delivery

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Diffusion of nanotechnology in cosmetics/skin care delivery Polymer skin delivery system designs provide considerable flexibility for formulators. Many of the polymers employed in these systems have bio and chemical compatibility with the drug and other components of the system such as penetration enhancers and pressure‐sensitive adhesives. They provide consistent, effective delivery of a drug throughout the product’s intended shelf life or delivery period and have generally‐recognized‐as‐safe status.

In polymeric systems used for transdermal delivery, the drug or polymer matrix is sandwiched between two polymeric layers: an outer impervious backing layer that prevents the loss of drug through the backing surface and an inner polymeric layer that functions as an adhesive and/or rate‐controlling membrane.

Dendrimers or fractal polymers, a new class of monodispersed macromolecules developed during the past decade, provide the key to manufacturing of functional nanoscale materials that would have unique properties (chemical, biological, optical) that could be the basis of new nanoscale technology and devices. They have a highly branched, tree‐like three‐dimentional structure compared to conventional polymers, which are linear or long chains. Dendrimers consist of a series of chemical shells built around a small core molecule and feature four main components: a central or core unit, arms of identical size, linking or branched points and end functional groups. They are grown around a core and cross‐linked to fix the structure. The terminal groups may be chemically different from the interior. The core can be removed to create a cavity.

The cavities are used as binding sites for small guest molecules that can be released in a slow equilibrium, making dendrimers promising slow delivery agents for perfumes and herbicides. When compared to their linear isomers, dendrimers are more soluble in common solvents that are not effective solvents for the linear isomer. In the pharmaceutical industry, fractal polymers are used to deliver drugs, chemical markers or genetic material right into cells or binding active particles to create an immune response. They are also used to create nanocapsules since dendrimers are amphilic and can self‐organize into nanoscale structures.

Dendrimers have applications in skin treatments, hair care, bath and shower products and fragrances. The surface activity of dendrimer branches arises from the hydrophobic edge parts, and the hydrophilic core, so that these branches tend to stand up on a water surface like a nano‐forest, cores (roots) going into the water, and the branches going up into the air. If a small amount of these dendrimers is spread, they form an extremely thin molecular film, only one molecule thick (a monolayer). A small addition of fractal polymer FPEC (fractal poly‐epsilon caprolactam), increases the efficiency of cleaning agents.

Diffusion of nanotechnology in food delivery

For delivery systems to be effective the encapsulated active compounds must be delivered to the appropriate sites, their concentration maintained at suitable levels for long periods of time, and their premature degradation prevented (Jelinski, 1999). Nanoparticles and nanospheres allow better encapsulation and release efficiency than traditional encapsulation systems, and are particularly attractive, since they are small enough to even be injected directly into the circulatory system (Bodmeier et al., 1989; Roy et al., 1999).

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Roy et al. (1999) showed that complex coacervates of DNA and chitosan could be used as delivery vehicles in gene therapy and vaccine design. Their work resulted in immunization of mice against peanut allergen gene, which indicates that oral immunization using DNA‐functionalized nanoparticles could become an effective treatment of food allergies, a very serious problem affecting a large number of consumers all over the world.

The efficiency of delivery systems can be enhanced using dendrimer‐coated particles. Dendrimers, macromolecules with a regular, highly branched 3‐dimensional structure, have a large number of functionalities due to the high local density of active groups. This characteristic makes them usable in a wide range of applications, such as sensors, catalysts, or agents for controlled release and site‐ specific delivery.

Manipulation of matter at the nanolevel also opens up possibilities for improving the functionality of food molecules, to the benefit of product quality. Dziechciarek et al. (1998) have developed starch‐ based nanoparticles that behave like colloids in aqueous solution, and can be used in food applications such as mixing, emulsification, and imparting specific theology to foods.

Research Question 3: What will be the impact of the diffusion of nanoplatform‐based delivery technologies (1) Pharmaceuticals/drug delivery, Cosmetics/skin care and Food R&D? and, (2) market and technological convergence between previously distinct indutries?

New Delivery Systems for Nutraceutical (Nutracosmetic) and Cosmeceutical Formulations

World consumers are focused on their health, wellbeing and appearance now more than ever before, with such terms as ‘natural’, ‘organic’, ‘no artificial preservatives’, ‘no animal ingredients’ and ‘non‐ animal tested’ drawing formidable attention. This trend is creating heightened demand for products formulated with nature‐based cosmeceutical and nutraceutical ingredients. Efficacious ingredients and innovative delivery systems are driving the new product development arena.

An innovative delivery system can improve both the aesthetics and performance of a cosmetic product. Most current delivery systems for nutraceutical products are based on direct ingestion. The oral delivery systems pose issues relative to their unacceptable odour and taste and degradation of nutraceutical itself during its transport from the digestive system to the site of desired action. The topical delivery systems circumvent some of these issues due to their application near or at the site of affliction. Nutraceutical and cosmeceutical ingredients are finding their applications in topical alternative medicine.

Nutracosmetics are an emerging class of health and beauty aid products. They combine the benefits of nutraceutical ingredients with the elegance, skin feel and delivery systems of cosmetics. Nutracosmetics and cosmeceuticals thus differ in the origin of their functional ingredients. Nutraceutical ingredients formulated in cosmetic delivery systems constitute nutracosmetics, whereas cosmeceuticals are cosmetics formulated with pharmaceutical‐type ingredients.

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The nutraceutical ingredients‐based topical delivery systems can be formulated as functional cosmetics (nutracosmetics) to complement the efficacy of their ingestion‐based counterparts. However, the product development of these functional cosmetics faces challenges unique to each nutraceutical ingredient and its targeted body organ for specific benefits, for example the inclusion of a dietary fibre in a functional cosmetic to provide reduced cancer risk. Benefits of the fibre are not viable due to insignificant absorption of that fibre through a topical delivery system. The incorporation of nutraceutical supplements in functional cosmetics requires special considerations relative to the aspects of product appearance, dosage level, cosmetic benefits, storage stability, bioavailability, efficacy and cost. These activities require a combination of cosmetic and pharmaceutical product development technologies.

It is envisioned that a combination of popular nutraceutical and cosmeceutical ingredients (see Table 6) in bioavailability enhancing topical delivery systems may offer advantages that may surpass their delivery by any single method alone. This aspect could open new marketing concepts to provide increased consumer awareness and appreciation for both nutraceutical and cosmeceutical ingredients in nutracosmetic delivery systems.

Table 6 Popular nutracosmetic ingredients

Strategies can be developed for other nutracosmetic and cosmeceutical ingredients in the design of successful new consumer products via their combination in proper delivery systems. The delivery systems are often designed based on the mode of product application and its packaging form. Opportunities for innovation will continue to exist for suppliers, formulators and marketers of nutracosmetics and cosmeceuticals.

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