Controlled release of macromolecules from PLA microspheres: using porous structure topology

Release of hydrophilic macromolecules (FITC-dextran, M-w=71 and 2000 kDa) from porous poly (D,L-lactic acid), PLA, microspheres was studied by applying percolation theory. Microspheres were prepared by the double emulsion method using high molecular weight PLA. The microspheres showed a percolation threshold, rho(C), at porosity 0.34. From this parameter, the effective diffusion coefficients, D-eff, and the accessible porosity (total releasable active ingredient), rho(A), of the microspheres were calculated using the Bethe lattice model with coordination number 4. Decreasing porosity of the microspheres decreased the release rate of the active ingredients and a long-term release was observed for the microspheres with porosity close to rho(C); The calculated rho(A) agreed with the experimental data and also the calculated D-eff for the microspheres with larger porosity (>0.4) was a good estimation to predict the experimentally determined release profiles by applying the continuum structure model (CSM). For microspheres with porosity larger than 0.4 which contained FITC-dextran M-w=71 kDa, a lag time was observed, which was attributed to delayed saturation of the microspheres with release medium. For microspheres with porosity close to rho(C), the limited number of exit holes on the exterior surface changed the mechanism of release and controlled the release rate rather than the tortuosity of the porous structure of the microspheres. (C) 2000 Elsevier Science B.V. All rights reserved.