Formulation and characterization of anticancer drug loaded targeted polymeric nanocarriers

The distribution of the drugs used in cancer chemotherapy without distinction between the diseased area and the healthy area causes damage to healthy tissue. By using targeted drug delivery systems it is intended to selectively accumulate cancer chemotherapy drugs at the diseased site, thus preventing healthy tissue damaging. Doxorubicin is an anticancer drug with serious side effects such as cardiotoxicity. In this study it was aimed to formulate and characterize a passive and active targeted drug delivery system by encapsulating doxorubicin to pH-sensitive polymeric micelles and by conjugating these micelles to peptide-18 which targets breast cancer cells. Due to its "stealth effect" and biocompatibility properties, poly(2-ethyl-2-oxazoline) was used as an alternative to poly(ethylene glycol) in the formulation of polymeric micelles. pH-sensitive poly(2-ethyl-2-oxazoline) and cationic poly(ethylenimine) containing block copolymers poly(2-ethyl-2-oxazoline)–b-poly(ε-caprolactone) and poly(2-ethyl-2-oxazoline)-co-poly(ethyleneimine)-b-poly(ε-caprolactone) were used for the preparation of doxorubicin loaded micelles. In vitro characterization studies such as micelle size, zeta potential, encapsulation efficiency, in vitro pH sensitive release studies and colloidal stability studies were performed for these formulations. Prepared formulations were evaluated in terms of biocompatibility with L929 fibroblast cells in cell culture and evaluated for their anticancer activity with MCF-7 and SKBR-3 breast cancer cells. Polymeric micelles prepared in this study are passive and active targeted formulations. They are able to encapsulate a large amount of doxorubicin, and are stable in neutral conditions (pH 7.4, blood circulation), while providing higher doxorubicin release in acidic conditions (tumor tissue and cells) and their anticancer effect is shown on MCF-7 and SKBR-3 breast cancer cells. The results showed that a new drug delivery system was developed which has the potential to be used for a more effective cancer treatment. Key words: Polymeric micelles, doxorubicine, targeted systems, poly (2-ethyl-2) oxazoline), cell culture