[摘要]：We propose the use of a new biopolymer, acetalated dextran (Ac-DEX), to synthesize porous microparticles for pulmonary drug delivery. Ac-DEX is derived from the polysaccharide dextran and, unlike polyesters, has tunable degradation from days to months and pH neutral degradation products. Ac-DEX microparticles fabricated through emulsion techniques were optimized using a variety of postprocessing techniques to enhance the respirable fraction for pulmonary delivery. Tangential flow filtration resulted in a maximum 37% respirable fraction for Ac-DEX porous microparticles, compared to a 10% respirable fraction for poly(lactic-co-glycolic acid) (PLGA) porous micropartides. Ac-DEX microparticles were of an optimum diameter to minimize macrophage clearance but had a low enough theoretical density for deep lung penetration. Transepithelial electrical resistance (TEER) measurements showed that the particles did not impinge on a monolayer of lung epithelial cells in either air or liquid conditions. Also, the release of the chemotherapeutic camptothecin was shown to be tunable depending on Ac-DEX degradation time and molecular weight, and drug release was shown to be bioactive over a range of concentrations. Our results indicate that both release kinetics and fraction of burst release of drug from Ac-DEX porous microparticles can be tuned by simply changing the Ac-DEX polymer properties, affording a large range of formulation options for drug delivery to the pulmonary cavity. Overall, Ac-DEX porous microparticles show promise as an emerging carrier for pulmonary delivery of drugs to the alveolar region of the lung, particularly for the treatment of lung diseases.
