Development of self assembled layer by layer polymeric carriers to deliver small and macromolecule therapeutics

Abstract

Rapid growth in the drug discovery science resulted in the development of potential newlinesmall molecule drugs and biotechnology based drugs including proteins and nucleic acids. newlineHowever, the clinical application of many new therapeutics is limited by inefficient drug newlinedelivery systems. There is a need for development of drug carriers which can deliver the newlinecargo in a stable and efficient manner. Recently, the self-assembled delivery systems have newlineshown potential as drug carriers with improved solubilisation of drugs, stimuli-responsive newlinetargeted delivery, reduced toxicity, achieving controlled release and protection of therapeutic newlineagent against biological degradation. Among the various self-assembly approaches reported newlinefor the fabrication of drug delivery carriers, the layer-by-layer (LbL) technique has gained newlinegreater interest. LbL assembly is a highly versatile technique, where polymers can be coated newlineon different sizes, shapes and surface chemistry. Essentially, the LbL technique involves newlinesequential adsorption of oppositely charged polyelectrolytes on a template. A planar template newlinewould result in the formation of a thin film, while a spherical sacrificial template would result newlinein the formation of a nano- or microcapsule. newlineThis dissertation explored the development of novel drug delivery carriers including newlinemicrocapsules and thin films using layer-by-layer technology for delivery of small and newlinemacro-molecule therapeutics. To this end, the overall objective of the study is fabrication and newlinecharacterization of layer-by-layer assembled microcapsules for systemic application and newlinelayer-by-layer thin films for topical application. newlineThe first objective was to investigate the influence of physical and chemical newlineproperties of active molecules on encapsulation in LbL-MC. Layer-by-layer microcapsules newline(LbL-MC) were prepared by sequential adsorption of poly(styrene sulfonate) (PSS) andpoly(ethyleneimine) (PEI) on calcium carbonate sacrificial templates. Model small moleculesvwith varying charge, anionic -ascorbic acid, indomethacin; cat