chitosan and plga microspheres as drug delivery ... - UniCA Eprints

7. RFP Loaded PLGA Coated Chitosan Microspheres Obtained by WSD MethodBiodegradable microparticles made of poly(lactide-co-glycolide) (PLGA) are well-establisheddelivery systems for therapeutics, and have a high potential for peptide, protein and othertherapeutic substances. Thanks to its established safety record, PLGA continues to beprevalently used in the field, although the stability of certain entrapped drug like protein,remains a major issue. Nevertheless, one of the typical deficiencies of aliphatic polyesterssuch as PLGA is their lack of suitable functional groups for an efficient and stable depositionor conjugation of bioactive agents under mild conditions. Surfaces coated with functionalpolymers or bearing bioactive ligands represent an increasingly desirable feature for drugdelivery through microparticulate or nanoparticulate systems besides controlled release andprotection of bioactive agents from premature clearance and degradation. Various approacheshave been proposed to functionalize the surface of biodegradable microparticles andnanoparticles. The negatively charged surface of PLGA microparticles has beenfunctionalized by the electrostatic binding of cationic surfactants such ascetyltrimethylammonium bromide (260). An alternative to cationic surfactants is theelectrostatic coating with polycationic polymers such as chitosan (261, 262, 263). Typically,the establishment of cationic microparticles surfaces may be performed by incubation ofpreviously prepared particles in an aqueous solution of the cationic agent. Direct coating ofnascent particles in the course of a typical solvent evaporation/extraction process is achievedby addition of cationic surfactants or polymers to the aqueous extraction phase (264, 265). Athird approach to obtain PLGA particles with cationic surface charge is the coencapsulation ofa cationic lipid or a polyelectrolyte through spray drying (266). The purpose of PLGAmicroparticles bearing a cationic surface charge may be to provide a positively chargedbinding site for the adsorption, condensation and stabilization of nucleic acidbiopharmaceuticals (plasmid DNA, mRNA), or antisense oligonucleotides, throughelectrostatic interaction (267, 268), or to render the particles mucoadhesive, e.g. in view ofnasal and pulmonary delivery (269).Chitosan is highly bioadhesive and has been reported to enhance the permeability of the nasalmucosa (270, 271, 272). Thus, besides offering a substrate for the adsorptive deposition orconjugation of bioactive ligands, chitosan microparticles feature intrinsic bioadhesive andpermeation enhancing properties, which make them particularly suitable for nasal andpulmonary administration.Results obtained with PLGA microspheres led us to develop a novel actively mucoadhesivePLGA microspheres system to improve pulmonary delivery of RFP by coating the particle102