Journal
JOURNAL OF CONTROLLED RELEASE
Volume 76, Issue 3, Pages 297-311Publisher
ELSEVIER
DOI: 10.1016/S0168-3659(01)00446-1
Keywords
pore size; PLGA degradation; protein molecular weight; erosion mechanism; microsphere
Funding
- NIGMS NIH HHS [1R01GM55245-01] Funding Source: Medline
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This study investigates the effect of protein molecular weight on release kinetics from polymeric microspheres (1-3 mum). Proteins were encapsulated at high and low loadings in poly(lactic-co-glycolic acid) (PLGA) by a phase inversion technique. Mechanism of release from this type of microsphere appeared to be dependent on protein molecular weight for microspheres with low loadings (0.5-1.6%), while independent of protein molecular weight for microspheres with high loadings (4.8-6.9%). At low loadings, release of larger proteins was dependent on diffusion through pores for the duration of the study, while smaller proteins seemed to depend on diffusion through pores initially and on degradation at later times. Following an initial diffusion phase from low loaded microspheres, lysozyme and carbonic anhydrase, the two smallest proteins, exhibited lag phases with curtailed protein release followed by a phase of increased protein release between 4 and 8 weeks, a phenomenon not evident for larger proteins. It appears that by 8 weeks, PLGA had degraded enough to allow additional release of smaller proteins which were entrapped efficiently within the microspheres. Higher loaded microspheres, which have more interconnecting channels. did not exhibit the pronounced shift from diffusion-based to polymer degradation-based release seen with the lower loaded microspheres. Interestingly, microspheres encapsulating large proteins maintained sustained release rates for 56 days. (C) 2001 Elsevier Science B.V. All rights reserved.
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