Interdependency of protein-release completeness and polymer degradation in PLGA-based implants

Release of BSA (model protein) from hot-melt extruded poly(lactide-co-glycolide) (PLGA)-based implants was incomplete. A residual mass of covalent BSA-PLGA adducts was still present after 6 months. The objective of this study was to increase the completeness of BSA release. BSA reduced the PLGA degradation and erosion rate as well as the extent of erosion. An increased uptake of release medium in the presence of BSA in addition to the early outflux of PLGA oligomers resulted in a reduction of the matrix acidity and thus reduction of autocatalysis effects. PLGA mass loss was incomplete at 60% and 80% for 10% and 25% BSA-containing implants. The extent of PLGA mass loss was correlated with the total releasable protein. The same release was obtained from implants prepared with pre-degraded PLGA suggesting that the induction phase did not affect the release completeness. Thus, the focus was on the erosion phase to enhance outflux of soluble oligomers. BSA release completeness increased by increasing the porosity of the implants at the onset of erosion phase. This could be obtained with a higher initial porosity, formation of porosity upon higher diffusional release and/or incorporation of pore-formers/plasticizers. Accordingly, the BSA release completeness could be improved by enhancing the outflux of soluble PLGA degradation products.