Synthesis, characterization and pharmaceutical application of selected copolymer nanoparticles / D.P. Otto
Otto, Daniël Petrus
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A multidisciplinary literature survey revealed that copolymeric nanoparticles could be applied in various technologies such as the production of paint, adhesives, packaging material and lately especially drug delivery systems. The specialized application and investigation of copolymers in drug delivery resulted in the synthesis of two series of copolymeric materials, i.e. poly(styrene-co-methyl methacrylate) (P(St-co-MMA)) and poly(styrene-co-ethyl methacrylate) (P(St-co-EMA)) were synthesized via the technique of o/w microemulsion copolymerization. These copolymers have not as yet been utilized to their full potential in the development of new drug delivery systems. However the corresponding hydrophobic homopolymer poly(styrene) (PS) and the hydrophilic homopolymer poly(methyl methacrylate) (PMMA) are known to be biocompatible. Blending of homopolymers could result in novel applications, however is virtually impossible due to their unfavorable mixing entropies. The immiscibility challenge was overcome by the synthesis of copolymers that combined the properties of the immiscible homopolymers. The synthesized particles were analyzed by gel permeation chromatography combined with multi-angle laser light scattering (GPC-MALLS) and attenuated total reflectance Fourier infrared spectroscopy (ATR-FTIR). These characterizations revealed crucial information to better understand the synthesis process and particle properties i.e. molecular weight, nanoparticle size and chemical composition of the materials. Additionally, GPC-MALLS revealed the copolymer chain conformation. These characterizations ultimately guided the selection of appropriate copolymer nanoparticles to develop a controlled-release drug delivery system. The selected copolymers were dissolved in a pharmaceutically acceptable solvent, tetrahydrofuran (THF) together with a drug, rifampin. Solvent casting of this dispersion resulted in the evaporation of the solvent and assembly of numerous microscale copolymer capsules. The rifampin molecules were captured in these microcapsules through a process of phase separation and coacervation. These microcapsules finally sintered to produce a multi-layer film with an unusual honeycomb structure, bridging yet another size scale hierarchy. Characterization of these delivery systems revealed that both series of copolymer materials produced films capable of controlling drug release and that could also potentially prevent biofilm adhesion.
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