Malign Gliomların Tedavisi Için Lipit İle İşlevselleştirilmiş Plga Nanopartiküllerinin Tasarımı, in Vitro ve in Vivo Değerlendirilmesi
Özet
A significant limiting factor in treating malignant glioma is the inability to deliver therapeutic concentrations of chemotherapeutic drugs to the tumor without incurring unacceptable systemic side effects. Another limiting factor is the Blood Brain Barrier (BBB) which hinders reaching of antineoplastic drugs to the brain. One of the approaches to overcome these difficulties is the preparation of nanoparticles using polyethylene glycol (PEG) or cationic lipid-PEG combination. In the present study, a new generation antineoplastic drug, farnesyl thiosalicylic acid (FTS) loaded Poly(Lactic-co-glycolic acid)-1,2– distearoyl- glycerol-3 phospho-ethanolamine-N [methoxy (polyethylene glycol) - 2000] ammonium salt (DSPE-PEG), PLGA-DSPE-PEG-(1,2-dioleyl-3-trimetilammonium-propane) (DOTAP) have been prepared and evaluated for in vitro characterization study (particle size, morphology, drug loading and in vitro drug release). Furthermore, cell culture studies and in vivo studies on glioma bearing rats have been done. Scanning Electron Microscopy studies showed that all formulations prepared had smooth surface and spherically shape. It has been found that the addition of DOTAP to the formulations changed the in vitro characteristics of the formulations. Cell culture studies have showed that FTS and FTS loaded nanoparticle formulations are active against RG2 glioma cell lines. The in vivo results have showed that the intratumorally administered formulations more reduced to the tumor in compared to intravenously administered formulations.
