Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers

Microspheres were prepared from poly(L-lactic acid) polymers having molecular weights between 500 and 50k g/mol. The polymers were synthesized using two initiator molecules, L-lactic acid oligomer (PLLA-LA) or stearyl alcohol (PLLA-SA). For both PLLA-LA and PLLA-SA polymers, glass (Tg) and melting (Tm) transition temperatures and enthalpy of melting all increased as the polymer molecular weight increased. PLLA-SA showed the greatest change in Tg (-13 to 54 degreesC) as molecular weight increased from 500 to 10k g/mol, compared to 25 to 55 degreesC for PLLA-LA polymers. Changes in Tm and enthalpy of melting with increasing molecular weight were similar for both PLLA-LA and PLLA-SA. Paclitaxel release From 30%, paclitaxel loaded microspheres in the size range of 50-90 mum was affected by these changes in polymer properties as molecular weight increased. As the molecular weight increased from 2k to 50k g/mol the amount of drug released from microspheres over 14 days decreased From 76 to 11% of the initial drug load. The release profiles were consistent with a diffusion controlled mechanism provided a two-compartment model was employed. According to this model, the total amount of 'available' drug (compartment 1) was released by diffusion in 14 days while the remainder (compartment 2) was confined within the polymeric matrix and could not diffuse out at a measurable rate. Following the in vitro release study, microsphere made from 2k-10k g/mol polymers showed significant signs of disintegration whereas 50k g/mol polymer microspheres remained intact. (C) 2001 Elsevier Science B.V. All rights reserved.