Biodegradable copolymers of glycolide, L-lactide, ε-caprolactone and trimethylene carbonate (TMC) are valuable approach in the use for local immunosuppressants delivery. The appropriate comonomers combining allows to obtain long-term drug release from polymeric matrice as a result of slow degradation process. However, development of method for adjusting the concentration of released therapeutical agent is very needed, too. The aim of this study was to assess the in vitro release of Sirolimus and CyA from different kinds of biodegradable copolymer matrices as well as correlation between the copolymers microstructure and drug release profile.

Different kinds of copolymers were used to prepare matrices containing 10% of CyA (92% ε-caprolactone 8% glycolide; 75% L-lactide 25% ε-caprolactone; 70% TMC 30% L-lactide) or Sirolimus (75% L-lactide 25% ε-caprolactone; 70% L-lactide 30% TMC; 70% TMC 30% L-lactide).The concentration of drug release from polymeric matrices in in-vitro environment has been determined by means of UV-Vis spectroscopy for 35 weeks. Analysis of changes in copolymers chain microstructure during the degradation process was conducted based on the parameters determined from ¹H NMR and ¹³C NMR spectra: the average length of the lactidyl, carbonate, glycolidyl and caproyl blocks (L_LL, L_T, L_GG L_Cap), intermolecular transestrification ratio (T_II) and the degree of chain randomization (R) [1,2].

According to the expectations, the used copolymers provided prolonged release of drugs in all cases. The process proceeded very steadily for Sirolimus, which correlated with small changes in copolymer chain microstructure during degradation. There were some more alterations in CyA release, as a consequence of more significant changes in copolymer chain structure. The differences between two studied drugs release have been noted even for the same kind of polymeric matrice as presented in Table 1

Table 1. The comparison of release profile of Sirolimus and CyA from L-lactide/TMC polymeric matrice and characteristic of copolymer chain microstructure changes during degradation.

This indicates the necessity of individual research for every therapeutical agent having different physico-chemical features, that incorporated in polymeric material may influence degradation process.

The results of the study demonstrate that CyA and Sirolimus release is strongly influenced by copolymeric chain microstructure and proceeds steadily according to small changes during the degradation.

References

[1] P. Dobrzyński, S. Li, J. Kasperczyk, M. Bero, F. Gasc, M. Vert, Structure-property relationships of copolymers obtained by ring-opening polymerization of glycolide and ε-caprolactone. Part 1. Synthesis and Characterization, Biomacromolecules 6 (2005) 483-488.

[2] P. Dobrzyński, J. Kasperczyk, M. Bero, Synthesis of biodegradable copolymers with low-toxicity zirconium compounds. V. Multiblock and random copolymers of L-lactide with trimethylene Carbonate obtained in copolymerization initiated with zirconium (IV) acetylacetonate. J. Polym. Sci. Part A (2006) in print

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