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Comparison of accelerated and real-time cyclosporine A release testing from poly(L-lactide-co-trimethylene carbonate) matrices

Katarzyna Jelonek 1Janusz Kasperczyk 1,2Piotr Dobrzynski 1Karolina Szczepka 2Bożena Jarząbek 1Joanna Jaworska 1Henryk Janeczek 1

1. Centre of Polymer and Carbon Materials, Polish Academy of Sciences, Zabrze 41-819, Poland
2. Department of Biopharmacy, Medical University of Silesia, Narcyzów 1, Sosnowiec 41-200, Poland


Cyclosporine A (CyA) is a cyclic undecapeptide, used in prophylaxis and therapy of graft rejection in all types of solid organ and bone narrow transplantation, as well as in treatment of a number of autoimmune diseases. However, prolonged repeated treatment with CyA may cause many side effects like nephrotoxicity, gingival hyperplasia and neurological disorders. Copolymers of TMC with L-lactide may be interesting in developing alternative delivery systems cyclosporine A. Accelerated CyA release testing is very desirable since long-time degradation of polymeric carrier. It can be achieved by the increase in polymer degradation via acid or alkali catalyzed hydrolysis, addition of surfactants to enhance drug diffusion or increase in temperature [1]. The aim of this study was to evaluate the usefulness of accelerated CyA release testing obtained by elevated temperature.

Poly(L-lactide-co-TMC) synthesized in Centre of Polymeric and Carbon Materials PASci in Zabrze, with using of Zr(Acac)4 as non toxic initiator of copolymerization reaction was used to prepare matrices with 2, 5 and 10 weight-% of cyclosporine A by solution casting method. Correlation between drug release testing conducted at 70oC the real-time release at 37oC was analyzed. The characteristic of copolymers microstructure during degradation process was conducted by means of high resolution NMR spectroscopy (AVANCE II Ultra Shield Plus, Bruker 600 MHz) [2]. CDCl3 was used as a solvent. The molecular weight (Mn) and molecular weight dispersion (D) were determined by GPC (Physics SP 8800 chromatograph), with chloroform as eluent. The thermal properties were examined by differential scanning calorimetry (DSC) with a TA DSC 2010 apparatus (TA Instruments, New Castle, DE).

The PLATMC characterized random structure (R=0,72). Thermal analysis showed that the used copolymer was amorphous with a glass transition temperature (Tg) at 42oC. Both, the analysis conducted at 37oC and 70oC showed that the highest amount of drug was released from matrices containing 2% of cyclosporine A and the lowest from matrices with the highest initial drug loading (10%). The accelerated cyclosporine A release testing can be a useful method of rapid polymer screening since the obtained results correlated with the real-time release.


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


[1] Kamberi M, Nayak S, Myo-Min K, Carter TP, Hancock L, Feder D. A novel accelerated in vitro release method for biodegradable coating of drug eluting stents: Insight to the drug release mechanisms. Europ J Pharm Sci 2009; 37: 217-222.

[2] Dobrzyński P, Kasperczyk J. 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: Polym Chem 2006; 44: 3184–3201.


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Submitted: 2010-03-14 23:01
Revised:   2010-03-20 18:44