Biochemistry and Pharmacology - Research Publications
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ItemLayer-By-Layer-Assembled Capsules and Films for Therapeutic Delivery(WILEY-V C H VERLAG GMBH, 2010-09-06)Polymeric materials formed via layer-by-layer (LbL) assembly have promise for use as drug delivery vehicles. These multilayered materials, both as capsules and thin fi lms, can encapsulate a high payload of toxic or sensitive drugs, and can be readily engineered and functionalized with specific properties. This review highlights important and recent studies that advance the use of LbL-assembled materials as therapeutic devices. It also seeks to identify areas that require additional investigation for future development of the field. A variety of drug-loading methods and delivery routes are discussed. The biological barriers to successful delivery are identified, and possible solutions to these problems are discussed. Finally, state-of-the-art degradation and cargo release mechanisms are also presented.
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ItemUptake and Intracellular Fate of Disulfide-Bonded Polymer Hydrogel Capsules for Doxorubicin Delivery to Colorectal Cancer Cells(AMER CHEMICAL SOC, 2010-05)Understanding the interactions between drug carriers and cells is of importance to enhance the delivery of therapeutics. The release of therapeutics into different intracellular environments, such as the lysosomes or the cell cytoplasm, will impact their pharmacological activity. Herein, we investigate the intracellular fate of layer-by-layer (LbL)-assembled, submicrometer-sized polymer hydrogel capsules in a human colon cancer derived cell line, LIM1899. The cellular uptake of the disulfide-stabilized poly(methacrylic acid) (PMA(SH)) capsules by colon cancer cells is a time-dependent process. Confocal laser scanning microscopy and transmission electron microscopy reveal that the internalized capsules are deformed in membrane-enclosed compartments, which further mature to late endosomes or lysosomes. We further demonstrate the utility of these redox-responsive PMA(SH) capsules for the delivery of doxorubicin (DOX) to colon cancer cells. The DOX-loaded PMA(SH) capsules demonstrate a 5000-fold enhanced cytotoxicity in cell viability studies compared to free DOX.
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ItemTargeting of Cancer Cells Using Click-Functionalized Polymer Capsules(AMER CHEMICAL SOC, 2010-11-17)Targeted delivery of drugs to specific cells allows a high therapeutic dose to be delivered to the target site with minimal harmful side effects. Combining targeting molecules with nanoengineered drug carriers, such as polymer capsules, micelles and polymersomes, has significant potential to improve the therapeutic delivery and index of a range of drugs. We present a general approach for functionalization of low-fouling, nanoengineered polymer capsules with antibodies using click chemistry. We demonstrate that antibody (Ab)-functionalized capsules specifically bind to colorectal cancer cells even when the target cells constitute less than 0.1% of the total cell population. This precise targeting offers promise for drug delivery applications.
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ItemNo Preview AvailableActive multilayered capsules for in vivo bone formation(NATL ACAD SCIENCES, 2010-02-23)Interest in the development of new sources of transplantable materials for the treatment of injury or disease has led to the convergence of tissue engineering with stem cell technology. Bone and joint disorders are expected to benefit from this new technology because of the low self-regenerating capacity of bone matrix secreting cells. Herein, the differentiation of stem cells to bone cells using active multilayered capsules is presented. The capsules are composed of poly-L-glutamic acid and poly-L-lysine with active growth factors embedded into the multilayered film. The bone induction from these active capsules incubated with embryonic stem cells was demonstrated in vitro. Herein, we report the unique demonstration of a multilayered capsule-based delivery system for inducing bone formation in vivo. This strategy is an alternative approach for in vivo bone formation. Strategies using simple chemistry to control complex biological processes would be particularly powerful, as they make production of therapeutic materials simpler and more easily controlled.
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ItemToward Therapeutic Delivery with Layer-by-Layer Engineered Particles(AMER CHEMICAL SOC, 2011-06)Layer-by-layer (LbL)-engineered particles have recently emerged as a promising class of materials for applications in biomedicine, with studies progressing from in vitro to in vivo. The versatility of LbL assembly coupled with particle templating has led to engineered particles with specific properties (e.g., stimuli-responsive, high cargo encapsulation efficiency, targeting), thus offering new opportunities in targeted and triggered therapeutic release. This Perspective highlights an important development by Poon et al. on tumor targeting in vivo using LbL-engineered nanoparticles containing a pH-responsive poly(ethylene glycol) (PEG) surface layer. Further, we summarize recent progress in the application of LbL particles in the fields of drug, gene, and vaccine delivery and cancer imaging. Finally, we explore future directions in this field, focusing on the biological processing of LbL-assembled particles.
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ItemPolymersome-Loaded Capsules for Controlled Release of DNA(WILEY-V C H VERLAG GMBH, 2011-07-18)The formation of a novel drug-delivery carrier for the controlled release of plasmid DNA that comprises layer-by-layer polymer capsules subcompartmentalized with pH-sensitive nanometer-sized polymersomes is reported. The amphiphilic diblock copolymer poly(oligoethylene glycol methacrylate)-block-poly(2-(diisopropylamino)ethyl methacrylate) forms polymersomes at physiological pH, but transitions to unimeric polymer chains upon acidification to cellular endocytic pH. These polymersomes can thus release an encapsulated payload in response to a change in pH from physiological to endocytic conditions. Multicomponent layer-by-layer capsules are formed by exploiting the ability of tannic acid to act as an efficient hydrogen-bond donor for both the polymersomes and poly(N-vinyl pyrrolidone) at physiological pH. These capsules show release of a plasmid DNA payload encapsulated within the polymersome subcompartments in response to changes in pH between physiological and endocytic conditions.
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ItemChallenges facing colloidal delivery systems: From synthesis to the clinic(ELSEVIER SCIENCE LONDON, 2011-06)