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Drug delivery methods can impact efficacy as much as the nature of the drug itself. Microparticles made of biodegradable polymers such as poly(D, l -lactide- co -glycolide) and poly(lactic acid) (PLA) have been studied extensively for controlled release of diverse drugs. By using a modified solvent extraction/evaporation method called precision particle fabrication (PPF), uniform microparticles such as single-wall microspheres, double-wall microspheres and liquid-core microcapsules have been fabricated with precise control of their geometric structures. By producing particles of uniform size, which has crucial impact on drug release behaviors, PPF-fabricated microparticles provide unique insights about drug release mechanism. Using small-molecule and macromolecule model drugs, our group demonstrated that physicochemical properties of the polymers and drugs and structural properties of the matrix can greatly impact drug distribution within microparticles, particle erosion and drug release rates. By careful selection of particle size and shell thickness, uniform microparticles can achieve “zero-order”, pulsatile or tandem release of drugs. [ABSTRACT FROM AUTHOR]

Purpose: Pulsatile delivery of proteins, in which release occurs over a short time after a period of little or no release, is desirable for many applications. This paper investigates the effect of biodegradable polymer shell thickness on pulsatile protein release from biodegradable polymer microcapsules. Methods: Using precision particle fabrication (PPF) technology, monodisperse microcapsules were fabricated encapsulating bovine serum albumin (BSA) in a liquid core surrounded by a drug-free poly(lactide- co-glycolide) (PLG) shell of uniform, controlled thickness from 14 to 19 μm. Results: When using high molecular weight PLG (Mw 88 kDa), microparticles exhibited the desired core-shell structure with high BSA loading and encapsulation efficiency (55-65%). These particles exhibited very slow release of BSA for several weeks followed by rapid release of 80-90% of the encapsulated BSA within 7 days. Importantly, with increasing shell thickness the starting time of the pulsatile release could be controlled from 25 to 35 days. Conclusions: Biodegradable polymer microcapsules with precisely controlled shell thickness provide pulsatile release with enhanced control of release profiles. [ABSTRACT FROM AUTHOR]

Abstract: Biodegradable polymer microparticles are promising delivery depots for protein therapeutics due to their relatively simple fabrication and facile administration. Double-wall microspheres (DWMS) comprising a core and shell made of two distinct polymers may provide enhanced control of the drug release profiles. Using precision particle fabrication (PPF) technology, monodisperse DWMS were fabricated with model protein bovine serum albumin (BSA)-loaded poly(lactide-co-glycolide) (PLG) core and drug-free poly(d,l-lactic acid) (PDLL) shell of uniform thickness. Monolithic single-wall microspheres were also fabricated to mimic the BSA-loaded PLG core. Using ethyl acetate and dichloromethane as shell- and core-phase solvents, respectively, BSA was encapsulated selectively in the core region within DWMS with higher loading and encapsulation efficiency compared to using dichloromethane as core and shell solvents. BSA in vitro release rates were retarded by the presence of the drug-free PDLL shell. Moreover, increasing PDLL shell thickness resulted in decreasing BSA release rate. With a 14-μm thick PDLL shell, an extended period of constant-rate release was achieved. [Copyright &y& Elsevier]