Controlled poly(l-lactide-co-trimethylene carbonate) delivery system of cyclosporine A and rapamycine--the effect of copolymer chain microstructure on drug release rate.

The effect of poly(L-lactide-co-TMC) chain microstructure (and its changes during degradation) on immunosuppressive drugs' release process was analyzed. Three kinds of poly(L-lactide-co-TMC) (PLATMC)--two semiblock and one random were used to prepare matrices containing cyclosporine A or rapamycine and drug free matrices. All of them degraded slowly enough to provide long term delivery of immunosuppressive agents. Moreover, copolymer chain microstructure determined the effect of drug loading on the degradation process. It was observed that matrices without drug obtained from semiblock copolymer degraded differently than matrices containing cyclosporine A or rapamycine, whereas all kinds of matrices obtained from random PLATMC degraded in similar way. This is the evidence that the only in case of semiblock copolymer factors concerning the presence of drug and the kind of drug influenced degradation process. Based on the obtained results, correlations between copolymer degradation and drug release process are proposed. According to our outcomes, regular drug release process may be obtained from highly randomized copolymers (R ≈ 1) that remain amorphous during degradation process. Determination of this factor may help in development of biodegradable systems, in which drug release rate and profile can be tailored by synthesis of polymer with appropriate chain microstructure.