Controlled doxorubicin delivery from photoresponsive liposomes carrying vitamin A derivatives


Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Orta Doğu Teknik Üniversitesi, Fen Bilimleri Enstitüsü, Fen Bilimleri Enstitüsü, Türkiye

Tezin Onay Tarihi: 2014

Öğrenci: SENEM HEPER

Danışman: VASIF NEJAT HASIRCI

Özet:

Drug delivery systems (DDS) have been an attractive approach to eliminate the drawbacks of conventional drug administration. Controlled and photoresponsive drug delivery systems have a special advantage; they deliver drugs more effectively. Liposomes are mostly preferred as drug carriers due to their ability to carry both hydrophilic and hydrophobic drugs, their being non-toxic and non-immunogenic. In this study, photoresponsive liposomes were prepared by incorporating vitamin A derivatives into the lipid bilayer of the liposomes for use in treatment of eye diseases that require frequent and continuous drug administration. Proliferative vitreoretinopathy was selected as a model disease and doxorubicin as the therapeutic agent. Doxorubicin loaded phosphatidyl choline (PC): cholesterol (CHOL): all-trans retinal (ATR) (7:1:3) liposomes were tested on RPE/D407 cells to determine the effect of UVA exposure (365 nm) on the release of doxorubicin, and therefore, cell viability. Among the different liposome compositions studied by exposing to UVA it was found that PC:CHOL:ATR (7:1:3) formulation responded the best. Antiproliferative effects of all-trans retinal (ATR) and doxorubicin were observedwhen tested on RPE/D407 cell line. Also, the interaction of the cells with doxorubicin and liposomes were studied with flow cytometry and confocal laser scanning microscopy (CLSM). It was found that liposomes or ATR can penetrate the cells while doxorubicin penetrates the nucleus.