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Droplet Microfluidics for Tumor Drug‐Related Studies And
REVIEW www.global-challenges.com Droplet Microfluidics for Tumor Drug-Related Studies and Programmable Artificial Cells Pantelitsa Dimitriou,* Jin Li, Giusy Tornillo, Thomas McCloy, and David Barrow* robotics, have promoted the use of in vitro Anticancer drug development is a crucial step toward cancer treatment, tumor models in high-throughput drug that requires realistic predictions of malignant tissue development and screenings.[2,3] High-throughput screens sophisticated drug delivery. Tumors often acquire drug resistance and drug for anticancer drugs have been, for a long efficacy, hence cannot be accurately predicted in 2D tumor cell cultures. time, limited to 2D culture of tumor cells, grown as a monolayer on the bottom of On the other hand, 3D cultures, including multicellular tumor spheroids a well of a microtiter plate. Compared to (MCTSs), mimic the in vivo cellular arrangement and provide robust 2D cell cultures, 3D culture systems can platforms for drug testing when grown in hydrogels with characteristics more faithfully model cell-cell interactions, similar to the living body. Microparticles and liposomes are considered smart matrix deposition and tumor microenvi- drug delivery vehicles, are able to target cancerous tissue, and can release ronments, including more physiological flow conditions, oxygen and nutrient gra- entrapped drugs on demand. Microfluidics serve as a high-throughput dients.[4] Therefore, 3D cultures have tool for reproducible, flexible, and automated production of droplet-based recently begun to be incorporated into microscale constructs, tailored to the desired final application. In this high-throughput drug screenings, with the review, it is described how natural hydrogels in combination with droplet aim of better predicting drug efficacy and microfluidics can generate MCTSs, and the use of microfluidics to produce improving the prioritization of candidate tumor targeting microparticles and liposomes. -
Application of Nucleic Acid–Lipid Conjugates for the Programmable Organisation of Liposomal Modules
Advances in Colloid and Interface Science 207 (2014) 290–305 Contents lists available at ScienceDirect Advances in Colloid and Interface Science journal homepage: www.elsevier.com/locate/cis Application of nucleic acid–lipid conjugates for the programmable organisation of liposomal modules Paul A. Beales a,⁎, T. Kyle Vanderlick b,⁎⁎ a School of Chemistry, University of Leeds, Leeds LS2 9JT, UK b Department of Chemical and Environmental Engineering, Yale University, New Haven, CT 06510, USA article info abstract Available online 27 December 2013 We present a critical review of recent work related to the assembly of multicompartment liposome clusters using nucleic acids as a specific recognition unit to link liposomal modules. The asymmetry in nucleic acid binding to its Keywords: non-self complementary strand allows the controlled association of different compartmental modules into com- Lipid vesicles posite systems. These biomimetic multicompartment architectures could have future applications in chemical DNA amphiphiles process control, drug delivery and synthetic biology. We assess the different methods of anchoring DNA to Directed assembly lipid membrane surfaces and discuss how lipid and DNA properties can be tuned to control the morphology Compartmentalization and properties of liposome superstructures. We consider different methods for chemical communication be- Bionanotechnology tween the contents of liposomal compartments within these clusters and assess the progress towards making this chemical mixing efficient, switchable and chemically specific. Finally, given the current state of the art, we assess the outlook for future developments towards functional modular networks of liposomes. © 2014 Elsevier B.V. All rights reserved. Contents 1. Introduction.............................................................. 290 2. FunctionalisationofliposomeswithDNA................................................. 292 2.1. Singlehydrocarbonchains................................................... -
Novel Liposomes for Targeted Delivery of Drugs and Plasmids
Brigham Young University BYU ScholarsArchive Theses and Dissertations 2013-11-15 Novel Liposomes for Targeted Delivery of Drugs and Plasmids Marjan Javadi Brigham Young University - Provo Follow this and additional works at: https://scholarsarchive.byu.edu/etd Part of the Chemical Engineering Commons BYU ScholarsArchive Citation Javadi, Marjan, "Novel Liposomes for Targeted Delivery of Drugs and Plasmids" (2013). Theses and Dissertations. 3879. https://scholarsarchive.byu.edu/etd/3879 This Dissertation is brought to you for free and open access by BYU ScholarsArchive. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of BYU ScholarsArchive. For more information, please contact [email protected], [email protected]. Novel Liposomes for Targeted Delivery of Drugs and Plasmids Marjan Javadi A dissertation submitted to the faculty of Brigham Young University in partial fulfillment of the requirements for the degree of Doctor of Philosophy William G. Pitt, Chair Morris D. Argyle Brad C. Bundy Alonzo D. Cook Randy S. Lewis Department of Chemical Engineering Brigham Young University November 2013 Copyright © 2013 Marjan Javadi All Rights Reserved ABSTRACT Novel Liposomes for Targeted Delivery of Drugs and Plasmids Marjan Javadi Department of Chemical Engineering, BYU Doctor of Philosophy People receiving chemotherapy not only suffer from side effects of therapeutics but also must buy expensive drugs. Targeted drug and gene delivery directed to specific tumor-cells is one way to reduce the side effect of drugs and use less amount of therapeutics. In this research, two novel liposomal nanocarriers were developed. This nanocarrier, called an eLiposome, is basically one or more emulsion droplets inside a liposome. -
Development of Artificial Cell Culture Platforms Using Microfluidics
DEVELOPMENT OF ARTIFICIAL CELL CULTURE PLATFORMS USING MICROFLUIDICS By HANDE KARAMAHMUTOĞLU Submitted to the Graduate School of Engineering and Natural Sciences in partial fulfillment of the requirements for the degree of Master of Science Sabanci University July 2019 DEVELOPMENT OF ARTIFICIAL CELL CULTURE PLATFORMS USING MICROFLUIDICS APPROVED BY Assoc. Prof. Dr. Meltem Elita¸s .............................................. (Thesis Supervisor) Assist. Prof. Dr. Murat Kaya Yapıcı .............................................. Assoc. Prof. Dr. Ali Özhan Aytekin .............................................. DATE OF APPROVAL: .............................................. ii © Hande Karamahmutoğlu 2019 All Rights Reserved iii ABSTRACT DEVELOPMENT OF ARTIFICIAL CELL CULTURE PLATFORMS USING MICROFLUIDICS HANDE KARAMAHMUTOGLU Mechatronics Engineering, MSc, Thesis, July 2019 Thesis Supervisor: Assoc. Prof. Dr. Meltem Elitas Key Words: Cell Culture, Cancer, Microfluidics, Lab-on-a-chip and Single-cell resolution. Acquiring quantitative data about cells, cell-cell interactions and cellular responses to surrounding environments are crucial for medical diagnostics, treatment and cell biology research. Nowadays, this is possible through microfluidic cell culture platforms. These devices, lab-on-a-chip (LOC), are capable of culturing cells with the feature of mimicking in vivo cellular conditions. Through the control of fluids in small volumes, LOC closely mimics the nature of cells in the tissues compared to conventional cell culturing platforms -
Development of an Artificial Cell, from Self- INAUGURAL ARTICLE Organization to Computation and Self-Reproduction
Development of an artificial cell, from self- INAUGURAL ARTICLE organization to computation and self-reproduction Vincent Noireauxa, Yusuke T. Maedab, and Albert Libchaberb,1 aUniversity of Minnesota, 116 Church Street SE, Minneapolis, MN 55455; and bThe Rockefeller University, 1230 York Avenue, New York, NY 10021 This contribution is part of the special series of Inaugural Articles by members of the National Academy of Sciences elected in 2007. Contributed by Albert Libchaber, November 22, 2010 (sent for review October 13, 2010) This article describes the state and the development of an artificial the now famous “Omnis cellula e cellula.” Not only is life com- cell project. We discuss the experimental constraints to synthesize posed of cells, but also the most remarkable observation is that a the most elementary cell-sized compartment that can self-reproduce cell originates from a cell and cannot grow in situ. In 1665, Hooke using synthetic genetic information. The original idea was to program made the first observation of cellular organization in cork mate- a phospholipid vesicle with DNA. Based on this idea, it was shown rial (8) (Fig. 1). He also coined the word “cell.” Schleiden later that in vitro gene expression could be carried out inside cell-sized developed a more systematic study (9). The cell model was finally synthetic vesicles. It was also shown that a couple of genes could fully presented by Schwann in 1839 (10). This cellular quantiza- be expressed for a few days inside the vesicles once the exchanges tion was not a priori necessary. Golgi proposed that the branched of nutrients with the outside environment were adequately intro- axons form a continuous network along which the nervous input duced. -
Lipodendriplexes a Promising Nanocarrier for Enhanced Gene
European Journal of Pharmaceutics and Biopharmaceutics 135 (2019) 72–82 Contents lists available at ScienceDirect European Journal of Pharmaceutics and Biopharmaceutics journal homepage: www.elsevier.com/locate/ejpb Research paper Lipodendriplexes: A promising nanocarrier for enhanced gene delivery with T minimal cytotoxicity Imran Tariqa,b, Shashank Reddy Pinnapireddya, Lili Dusea, Muhammad Yasir Alia,c, Sajid Alia, ⁎ Muhammad Umair Amina, Nathalie Goergena, Jarmila Jedelskáa, Jens Schäfera, Udo Bakowskya, a Department of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, Germany b Punjab University College of Pharmacy, University of the Punjab, 54000 Lahore, Pakistan c Faculty of Pharmaceutical Sciences, GC University Faisalabad, Faisalabad, Pakistan ARTICLE INFO ABSTRACT Keywords: Non-viral vectors are a safe, efficient and non-toxic alternative to viral vectors for gene therapy against many Liposomes diseases ranging from genetic disorders to cancers. Polyamidoamine (PAMAM), a positively charged dendrimer PAMAM has a tendency to complex with nucleic acids (to form dendriplexes) like plasmid DNA (pDNA) and small in- Dendriplexes terfering RNA (siRNA) and can shield them from enzymatic degradation, thereby facilitating endocytosis and Transfection endosomal release. In this study, we developed an advanced variant of the dendriplexes by encapsulating them Gene therapy within liposomes to enhance their gene delivery efficiency. This liposome encapsulated dendriplex system can Biocompatible CAM further reduce unwanted cytotoxicity and enhance cellular uptake of nucleic acids. A broad range of lipid combinations were used to optimize the lipodendriplexes in terms of their physicochemical characteristics in- cluding size, shape and zeta potential. The optimized lipodendriplexes were tested for pDNA transfection, in vitro cell viability, cellular uptake, siRNA mediated knockdown, hemocompatibility, metastatic progression and in ovo in chorioallantoic membrane model (CAM). -
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Lab on a Chip View Article Online TUTORIAL REVIEW View Journal | View Issue Droplet microfluidics for the construction of Cite this: Lab Chip,2018,18,2488 compartmentalised model membranes T. Trantidou, †a M. S. Friddin, †a A. Salehi-Reyhani, †abc O. Ces *abc and Y. Elani *abc The design of membrane-based constructs with multiple compartments is of increasing importance given their potential applications as microreactors, as artificial cells in synthetic-biology, as simplified cell models, and as drug delivery vehicles. The emergence of droplet microfluidics as a tool for their construction has allowed rapid scale-up in generation throughput, scale-down of size, and control over gross membrane ar- chitecture. This is true on several levels: size, level of compartmentalisation and connectivity of compart- ments can all be programmed to various degrees. This tutorial review explains and explores the reasons behind this. We discuss microfluidic strategies for the generation of a family of compartmentalised systems Received 10th January 2018, that have lipid membranes as the basic structural motifs, where droplets are either the fundamental build- Accepted 20th June 2018 Creative Commons Attribution 3.0 Unported Licence. ing blocks, or are precursors to the membrane-bound compartments. We examine the key properties as- sociated with these systems (including stability, yield, encapsulation efficiency), discuss relevant device fab- DOI: 10.1039/c8lc00028j rication technologies, and outline the technical challenges. In doing so, we critically review the state-of- rsc.li/loc play in this rapidly advancing field. 1. Introduction Membranes comprised of phospholipid bilayers are essential a Department of Chemistry, Imperial College London, London, SW7 2AZ, UK. -
(12) United States Patent (10) Patent No.: US 6,565,889 B2 Zasadzinski Et Al
USOO6565889B2 (12) United States Patent (10) Patent No.: US 6,565,889 B2 Zasadzinski et al. 45) Date of Patent: MaV 20,9 2003 (54) BILAYER STRUCTURE WHICH (56) References Cited ENCAPSULATES MULTIPLE CONTAINMENT UNITS AND USES U.S. PATENT DOCUMENTS THEREOF 4,078,052 A 3/1978 Papahadjopoulos 5,004,566 A 4/1991 Schnur et al. .............. 260/403 (75) Inventors: Joseph A. Zasadzinski, Santa Barbara, 5,492,696 A 2/1996 Price et al. ................. 424/417 CA (US); Scott A. Walker, White Bear 5,618,560 A 4/1997 Bar-Shalom et al. ....... 424/486 Lake, MN (US); Michael T. Kennedy, 5,643,574 A 7/1997 Gould-Fogerite etal. 424/184.1 Oak Park, CA (US); Edward T. Kisak, 5,723,147 A 3/1998 Kim et al. Santa it's Bret A. 5,855,911. A * 1/1999 Lopez-Berestein et al. 424/450 Coldren, Santa Barbara, CA (US) 6,045,955 A 4/2000 Vincent (73) Assignee: The Regents of the University of OTHER PUBLICATIONS California, Oakland, CA (US) Allen, T. M., Current Opinion in Colloid and Interface * ) Notice: Sub disclai h f thi Science 1, 645–651 (1996) (Exhibit 32). (*) Otice: tE. EME Lasic, D. D. et al., Current Opinion in Solid State and U.S.C. 154(b) by 0 days. Materials Science, 1,392–400 (1996) (Exhibit 33). Whitesides,IleSideS, T.1. H.Fl. and RossKOSS J. ColloidCOttola and Interface SScience, 169, 48–59 (1995) (Exhibit 34). (21)21) Appl.ppl. No.:No 09/842,2401842, Zasadzinski, J. A., Current Opinion in Solid State and Materials Science 2, 345–349 (1997) (Exhibit 35). -
Lipid Nanoformulations for Oral Delivery of Bioactives: an Overview
Send Orders for Reprints to [email protected] Current Drug Therapy, 2014, 9, 35-46 35 Lipid Nanoformulations for Oral Delivery of Bioactives: An Overview Ranjana Gupta1, Anant Agrawal1, Md. Meraj Anjum2, Harinath Dwivedi1, Koshy M. Kymonil1 2, and Shubhini A. Saraf * 1Faculty of Pharmacy, Babu Banarasi Das National Institute of Technology and Management, Lucknow, India; 2Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, India Abstract: Oral drug delivery has always been considered the preferred route of drug administration. Nano-formulations are now constantly being researched for better absorption, higher bioavailability and greater therapeutic efficacy. Lipid based nanoformulations have found much favour with the formulation scientist due to their relatively higher safety profile and enhancement of bioavailability. These delivery systems are also able to protect the bioactives or drugs from the vagaries of the gastrointestinal tract. They also aid in the absorption of hydrophobic drugs which are entrapped in lipid matrices. Lipid excipients have been known to reduce efflux which is P-glycoprotein mediated and also to increase the bioavailability of bioactives which are given through the oral route. In the last 20 years, about a thousand articles and reviews about oral lipid carriers have been reported. Many dosage forms have been made by modifying liposome, sometimes to overcome a disadvantage and at other times to modify the dosage form in such a manner so as to suit the requirement of the drug molecules. Various other lipidic drug delivery systems also exist which are not vesicular but being made of lipids, are equally useful for delivering lipophilic drugs. Although a Lipid Formulation Classification System exists, but there is no exhaustive review which discusses the entire lipid based, oral nanoformulations. -
Darwinian Evolution in a Translation-Coupled RNA Replication System Within a Cell-Like Compartment
ARTICLE Received 28 Mar 2013 | Accepted 22 Aug 2013 | Published 3 Oct 2013 DOI: 10.1038/ncomms3494 Darwinian evolution in a translation-coupled RNA replication system within a cell-like compartment Norikazu Ichihashi1,2, Kimihito Usui1, Yasuaki Kazuta1, Takeshi Sunami1,2, Tomoaki Matsuura1,2,3 & Tetsuya Yomo1,2,4 The ability to evolve is a key characteristic that distinguishes living things from non-living chemical compounds. The construction of an evolvable cell-like system entirely from non-living molecules has been a major challenge. Here we construct an evolvable artificial cell model from an assembly of biochemical molecules. The artificial cell model contains artificial genomic RNA that replicates through the translation of its encoded RNA replicase. We perform a long-term (600-generation) replication experiment using this system, in which mutations are spontaneously introduced into the RNA by replication error, and highly replicable mutants dominate the population according to Darwinian principles. During evolution, the genomic RNA gradually reinforces its interaction with the translated replicase, thereby acquiring competitiveness against selfish (parasitic) RNAs. This study provides the first experimental evidence that replicating systems can be developed through Darwinian evolution in a cell-like compartment, even in the presence of parasitic replicators. 1 Exploratory Research for Advanced Technology, Japan Science and Technology Agency, Osaka University, Suita, Osaka 565-0871, Japan. 2 Graduate School of Information Science and Technology, Osaka University, Suita, Osaka 565-0871, Japan. 3 Graduate School of Engineering, Osaka University, Suita, Osaka 565-0871, Japan. 4 Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan. Correspondence and requests for materials should be addressed to T.Y. -
(LDDS): Recent Advances and Applications of Lipids in Drug Delivery
Vol. 7(48), pp. 3034-3059, 29 December, 2013 DOI: 10.5897/AJPPX2013.0004 African Journal of Pharmacy and ISSN 1996-0816 © 2013 Academic Journals http://www.academicjournals.org/AJPP Pharmacology Review Lipid-based drug delivery systems (LDDS): Recent advances and applications of lipids in drug delivery Salome Amarachi Chime* and Ikechukwu V. Onyishi Department of Pharmaceutical Technology and Industrial Pharmacy, University of Nigeria, Nsukka 410001, Nigeria. Accepted 3 December, 2013 Recently, advances in pharmaceutical research is focused on new delivery systems utilizing new devices to achieve modification of delivery time, targeting, as well as improve the in vivo solubility and hence bioavailability of poorly soluble drugs. Lipid based drug delivery systems (LDDS) consists of diverse group of formulations, each consisting of varying functional and structural properties that are amenable to modifications achieved by varying the composition of lipid excipients and other additives. LDDS has evolved, overtime, from micro- to nano-scale enhancing the efficacy and therapeutic application of these systems. LDDS are accepted, proven, commercially viable strategies for formulating challenging pharmaceutical molecules and can be tailored to meet a wide range of product requirements. Generally, most lipid drug delivery systems used as drug carriers have high stability, high carrier capacity, feasibility of incorporating both hydrophilic and hydrophobic substances and feasibility of variable routes of administration, including oral, topical, -
Clusters of Nanoscale Liposomes Modulate the Release Of
Article Cite This: ACS Appl. Nano Mater. 2019, 2, 7134−7143 www.acsanm.org Clusters of Nanoscale Liposomes Modulate the Release of Encapsulated Species and Mimic the Compartmentalization Intrinsic in Cell Structures † † † † Igor Kevin Mkam Tsengam, Marzhana Omarova, Lauren Shepherd, Nicholas Sandoval, ‡ § † Jibao He, Elizabeth Kelley, and Vijay John*, † ‡ Department of Chemical & Biomolecular Engineering and Coordinated Instrumentation Facility, Tulane University, 6823 St. Charles Avenue, New Orleans, Louisiana 70118, United States § Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, Maryland 20899, United States *S Supporting Information ABSTRACT: We report the ability to place a high concentration of liposomes in a confined volume as a multicompartment cluster that mimics biological cells and allows for the modulation of release of encapsulated species. The formation of these coated multicompartmental structures is achieved by first binding liposomes into clusters before encapsulating them within a two-dimensional metal−organic framework composed of tannic acid coordinated with a metal ion. The essential feature is a molecularly thin skin over a ssystem of clustered liposomes in a pouch. The structural features of these pouches are revealed by small-angle scattering and electron microscopy. Through cryogenic electron microscopy, clusters with intact liposomes are observed that appear to be encapsulated within a pouch. Small-angle X-ray scattering shows the emergence of a relatively weak Bragg peak at q = 0.125 Å−1, possibly indicating the attachment of the bilayers of adjacent liposomes. The metal−phenolic network (MPN) forms a nanosized conformal coating around liposome clusters, resulting in the reduced release rate of the encapsulated rhodamine B dye.