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Effective Use of Nanocarriers As Drug Delivery Systems for the Treatment of Selected Tumors

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Effective Use of Nanocarriers As Drug Delivery Systems for the Treatment of Selected Tumors Journal name: International Journal of Nanomedicine Article Designation: Review Year: 2017 Volume: 12 International Journal of Nanomedicine Dovepress Running head verso: Din et al Running head recto: Effective use of nanocarriers for the treatment of selected tumors open access to scientific and medical research DOI: http://dx.doi.org/10.2147/IJN.S146315 Open Access Full Text Article REVIEW Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors Fakhar ud Din1,* Abstract: Nanotechnology has recently gained increased attention for its capability to effec- Waqar Aman2,* tively diagnose and treat various tumors. Nanocarriers have been used to circumvent the problems Izhar Ullah3 associated with conventional antitumor drug delivery systems, including their nonspecificity, Omer Salman Qureshi4 severe side effects, burst release and damaging the normal cells. Nanocarriers improve the Omer Mustapha5 bioavailability and therapeutic efficiency of antitumor drugs, while providing preferential accu- Shumaila Shafique6 mulation at the target site. A number of nanocarriers have been developed; however, only a few of them are clinically approved for the delivery of antitumor drugs for their intended actions at Alam Zeb7 the targeted sites. The present review is divided into three main parts: first part presents intro- 1 Department of Pharmacy, Quaid- duction of various nanocarriers and their relevance in the delivery of anticancer drugs, second i-Azam University, Islamabad, 2Department of Pharmacy, Kohat part encompasses targeting mechanisms and surface functionalization on nanocarriers and third University of Science and Technology, part covers the description of selected tumors, including breast, lungs, colorectal and pancreatic 3 Kohat, Department of Health and tumors, and applications of relative nanocarriers in these tumors. This review increases the Medical Sciences, University of Poonch, Rawalakot, Azad Kashmir, understanding of tumor treatment with the promising use of nanotechnology. 4Faculty of Pharmacy, University of Keywords: nanocarriers, drug delivery, solid lipid nanoparticles, liposomes, polymeric Lahore, Lahore, 5Faculty of Pharmacy, nanoparticles, dendrimers, breast tumor, lungs tumor, colorectal tumor, prostate tumor Ziauddin University, Karachi, 6Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Dow University of Health Sciences, Introduction to nanocarriers Karachi, 7Riphah Institute of Nanocarriers are colloidal drug carrier systems having submicron particle size Pharmaceutical Sciences, Riphah 1 International University, Islamabad, typically ,500 nm. Nanocarriers have been extensively investigated in the past few Pakistan decades as they showed great promise in the area of drug delivery. Nanocarriers, owing *These authors contributed equally to their high surface area to volume ratio, have the ability to alter basic properties to this work and bioactivity of drugs. Improved pharmacokinetics and biodistribution, decreased toxicities, improved solubility and stability, controlled release and site-specific delivery of therapeutic agents are some of the features that nanocarriers can incorporate in drug delivery systems.2,3 Moreover, the physiochemical properties of nanocarriers can be tuned by altering their compositions (organic, inorganic or hybrid), sizes (small or Correspondence: Alam Zeb Riphah Institute of Pharmaceutical large), shapes (sphere, rod or cube) and surface properties (surface charge, functional Sciences, Riphah International University, groups, PEGylation or other coating, attachment of targeting moieties).4 The overall Sector G-7/4, 7th Avenue, Islamabad 44000, Pakistan goal of utilizing nanocarriers in drug delivery is to treat a disease effectively with Tel +92 51 289 1835 minimum side effects.2 Fax +92 51 835 0180 Email [email protected] Anticancer chemotherapeutics when delivered via conventional drug delivery systems present a number of unique problems, including poor specificity, high Izhar Ullah toxicity and induction of drug resistance.5 These obstacles decrease the therapeutic Department of Health and Medical Sciences, Old Campus, University value of many anticancer drugs. Nanocarrier-based platforms have enabled effective of Poonch, Hajira Road, Shamsabad, delivery of anticancer drugs into the tumors by exploiting the pathophysiology of Rawalakot 12350, Azad Kashmir, Pakistan Email [email protected] tumor microenvironment, thereby significantly improving the therapeutic outcomes submit your manuscript | www.dovepress.com International Journal of Nanomedicine 2017:12 7291–7309 7291 Dovepress © 2017 Din et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/IJN.S146315 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Din et al Dovepress for oncological conditions.6 Furthermore, the overexpressed receptors on tumor cells surface have also been targeted with 6XUIDFWDQW nanocarriers platforms decorated with targeting ligands. &RVXUIDFWDQW A number of nanocarrier-based products have been approved for the treatment of various tumors, and many others are in /LSLGPDWUL[ different phases of clinical trials.4 In the current review, we first discussed features of different types of nanocarriers (organic, inorganic and hybrid) along with their relevance in cancer therapy. We then elaborated the targeting mechanisms and surface functionalization on nanocarriers to improve their targetability. Finally, we discussed selected tumors /RDGHGGUXJ and application of nanocarriers in the respective tumor. Figure 1 Schematics of SLN. Abbreviation: SLN, solid lipid nanoparticle. Organic nanocarriers Solid lipid nanoparticles (SLNs) make them promising nanocarriers to overcome or at least SLNs, developed in early 1990s, are nanosized colloidal minimize the drawbacks of conventional chemotherapy. drug carriers in the size range of 50–1,000 nm.7 SLNs are SLNs provide a natural platform to incorporate lipophilic prepared by dispersing melted solid lipid(s) in water, whereas anticancer drugs. Moreover, recent advances in the field of emulsifier(s) are used to stabilize the dispersion. The two most SLNs (eg, polymer–lipid hybrid type of SLNs, lipid–drug commonly used methods for preparing SLNs are high pres- conjugate nanoparticles [NPs]) made it possible to incorpo- sure homogenization and microemulsification. SLNs provide rate hydrophilic and ionic anticancer drugs as well. However, a highly lipophilic lipid matrix for drugs to be dispersed or quick elimination of SLNs from the blood flow by reticule dissolved.8 A wide variety of solid lipids including mono-, endothelial system (RES), encapsulation of hydrophilic di- and triglycerides; free fatty acids; free fatty alcohols; and ionic anticancer drugs and controlling the rate and waxes and steroids have been utilized for the preparation of extent of drug release from SLNs are the major obstacles SLNs. SLNs are quite similar to nanoemulsions except that faced by SLNs that restrain them from becoming effective different kinds of lipids are used in both the formulations. nanocarriers in anticancer drug delivery. All of these aspects Lipids that are solid at room temperature are used in SLNs of SLNs as anticancer drug carriers have been excellently instead of liquid lipids (oils) used in nanoemulsions.9 reviewed by Wong et al.5 Few examples where SLN systems SLNs as nanocarriers offer a number of advantages have been utilized for the delivery of anticancer drugs are over their colloidal counterparts, including nanoemulsions, docetaxel,13 doxorubicin,14 paclitaxel,15 methotrexate16 and liposomes and polymeric nanoparticles (PNPs). Some of the 5-fluorouracil (5-FU).17 areas where SLNs score better than their counterparts include controlled drug delivery, lack of biotoxicity, high drug pay- Liposomes load, improved bioavailability of poorly water-soluble drugs, Liposomes attained a great attention during the last few better stability and easy as well as economical large-scale decades in biomedicine, especially as a drug delivery system production.10,11 Various models have been proposed to incor- for antitumor drugs.18 They showed a number of advantages porate drugs into SLNs. Depending upon the composition of over conventional systems which are, but not limited to, SLNs (lipid, drug and surfactant) and production conditions enhanced delivery of drug, protection of active drug from (hot or cold homogenization), drug can either be dispersed environmental factors, improved performance features of the homogeneously in lipid matrix (solid solution/homogeneous product, preventing early degradation of the encapsulated matrix model) of SLNs (Figure 1), incorporated into the shell drug, cost-effective formulations of expensive drugs and effi- surrounding the lipid core (drug-enriched shell model) or cient treatment with reduced systemic toxicity.19 Moreover, incorporated into the core surrounded by a lipid shell (drug- drugs associated with liposomes have markedly altered
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