Preparation and evaluation of microparticles from thiolated polymers via air jet milling

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Microparticles were formulated by incorporation of the model protein horseradish peroxidase in (thiolated) chitosan and (thiolated) poly(acrylic acid) via co-precipitation. Dried protein/polymer complexes were ground with an air jet mill and resulting particles were evaluated regarding size distribution, shape, zeta potential, drug load, protein activity, release pattern, swelling behaviour and cytotoxicity. The mean particle size distribution was 0.5–12 μm. Non-porous microparticles with a smooth surface were prepared. Microparticles from (thiolated) chitosan had a positive charge whereas microparticles from (thiolated) poly(acrylic acid) were negatively charged. The maximum protein load for microparticles based on chitosan, chitosan–glutathione (Ch–GSH), poly(acrylic acid) (PAA) and for poly(acrylic acid)–glutathione (PAA–GSH) was 7 ± 1%, 11 ± 2%, 4 ± 0.2% and 7 ± 2%, respectively. The release profile of all microparticles followed a first order release kinetic. Chitosan (0.5 mg), Ch–GSH, PAA and PAA–GSH particles showed a 31.4-, 13.8-, 54.2- and a 42.2-fold increase in weight, respectively. No significant cytotoxicity could be found. Thiolated microparticles prepared by jet milling technique were shown to be stable and to have controlled drug release characteristics. After further optimizations the preparation method described here might be a useful tool for the production of protein loaded drug delivery systems.

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