Nanotech 2010

Inhibition of recurrence of Craniopharyngiomas by the controlled release of imatinib from PLGA microspheres

O. Karal Yilmaz, M. Kukut, E. Akgun, K. Baysal, T. Kilic
TUBITAK MRC, TR

Keywords: PLGA, microsphere, controlled release, craniopharyngiomas, imatinib

Abstract:

Craniopharyngiomas are histologically benign epithelial neoplasms of the suprasellar region that often exhibit aggressive and invasive growth . Although they may be totally excised by operation, recurrence of tumor is an important property of craniopharyngiomas. The biological behavior of these tumors are directly related to vascularization[1]. It was thought that tumor proliferation, spread and recurrence are dependent on angiogenesis. Experiments have been performed to verify our hypothesis that the recurrence of craniopharyngiomas, which have a cystic component and show high PDGF activity, is in direct relation with angiogenic activity of these tumors. So, angiogenic activities of tumor samples has been investigated by immunohistochemistry staining. For each tumor sample, angiogenic potentials have correlated retrospectively with recurrence in the patient from which it was derived. So it has been seen that recurrent tumors show higher angiogenic activities than non-recurrent tumors. In this study, we aim to test the inhibition of craniopharyngioma tumor recurrence by controlled release of imatinib using biodegradable poly (lactide-co-glycolide) copolymer (PLGA) microspheres. PLGA is a Food and Drug Administration-approved biodegradable polymer that is hydrolyzed in the body to its original non-toxic monomers, lactic acid and glycolic acid [2]. An attractive method that would permit delivery directly to the site of tumor is the use of polymers such as PLGA that are formed into small diameter microspheres. Microspheres have been proven to be efficient systems for delivery of a wide range of chemotherapeutic drugs to the brain [3]. In this work, PLGA microspheres containing imatinib agent were synthesized using a modified double emulsion-solvent evaporation method. The microspheres were characterized by their morphology (SEM analysis), size distribution (dynamic laser light scattering spectrometry), entrapment efficiency and release studies (HPLC). The inhibitory effects of imatinib on craniopharyngiomas was investigated on animals by “Rat Corneal Angiogenesis Model”. Firstly, angiogenic potential between recurrent and non-recurrent craniopharyngiomas were tested and a difference between two tumors was observed. Recurrent craniopharyngiomas showed higher angiogenic activity. Secondly, imatinib containing PLGA microspheres was implanted into corneas of rats in order to test the inhibition of recurrence. A decrease of angiogenesis in craniopharyngioma samples was observed. It can be concluded that imatinib loaded PLGA microspheres can be used as an efficient therapeutic delivery device for brain tumors.
 
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