Biodegradable polymers have become common materials used in pharmacy and medicine due to their properties such as mechanical strength, biocompatibility and non-toxic degradation products. Synthetic homopolymers, copolymers and terpolymers obtained from glycolide, lactide, ε-caprolactone and trimethylene carbonate (TMC) may serve as implants, scaffolds in tissue engineering and drug delivery systems. Different compositions of copolymers and their chain microstructure may have an effect on matrices degradation and thus, the drug release profile. The subject of our study was the influence of paclitaxel content on hydrolytic degradation of terpolymeric matrices. The determined factors may be helpful in designing biodegradable systems of controlled paclitaxel release. Paclitaxel belongs to antiproliferative drugs used in cancer treatment because of binding to the microtubuli and inhibiting cells proliferation. Its effectiveness in preventing of in-stent restenosis has also been reported. With this regard bioabsorbable matrices with suitable paclitaxel release profile may serve as drug-eluting stent or stent coating.

The terpolymers were synthesized in the Centre of Polymeric and Carbon Materials, Polish Academy of Sciences in Zabrze. Zr(Acac)₄ was used as the initiator. Matrices containing  5% and 10% (w/w) of paclitaxel were prepared form three kinds of terpolymers: 2 poly(L-lactide-co-glycolide-co-TMC) with different composition (51:26:23 and 62:27:11) and poly(L-lactide-co-glycolide- co-ε-caprolactone) (44:32:24). Hydrolytic degradation of three kinds of matrices prepared from each kind of terpolymer (matrice with 10% of paclitaxel, matrices with 5% of paclitaxel and drug free matrices) was performed in vitro at 37 °C in PBS.

The ¹H and ¹³C NMR spectra of terpolymers were recorded in order to characterize chain microstructure and paclitaxel content. Thermal properties were monitored by differential scanning calorymetry (DSC). Molecular weight dispersity (D) and molecular weight (Mn) were determined using gel permeation chromatography (GPC). The surface morphology of the matrices before and after degradation were studied by means of the scanning electron microscopy (SEM).

The impact of paclitaxel content (5% and 10% w/w) on hydrolytic degradation of matrices was investigated with reference to drug free matrices. Differences in degradation process of each kind of terpolymer were determined. The most significant degradation was observed in case of poly(L-lactide-co-glycolide-co-ε-caprolactone) 44:32:24, which become disintegrated after 2 weeks of incubation. Differences in degradation of matrices with paclitaxel and drug free matrices were noticed. This fact was also confirmed by analysis of surface morphology by means of  SEM.

Acknowledgement: This study has been financially supported by MEMSTENT (Grant No: UDA-POIG.01.03.01-00-123/08-00).

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