Abstract—Biodegradable polymeric micelles encapsulating doxorubicin in the core region were prepared from a grafted copolymer composed of O-Succinyl chitosan and Pluronic® F127. This copolymer was prepared by grafting Pluronic® F127 onto chitosan using 1-ethyl-3-(3-dimethylaminopropyl) -carbodi imide (EDC) and N-hydroxysuccinimide (NHS) as coupling agents. This polymeric micelles are self-assemblies of block copolymers of approximately 50 nm diameter in aqueous media. Anti-cancer drug (doxorubicin, DOX) can be loaded with high encapsulation efficiency (73.69 ± 0.53% to 74.65 ± 0.44%). An in vitro release study shows that the nanoparticle formulation exhibited a biphasic drug release with a moderate initial burst, followed by a sustained release profile in both pH 5.0 and pH 7.5 receiving media. The drug was rapidly and completely released from the nanoparticles at pH 5.0 nearly 100%, whereas, at pH 7.4, only 73.51 ± 2.68% to 90.26 ± 0.94% of DOX was released within 22 days. From the in vitro cytotoxicity test, DOX-NPs showed high cytotoxicity against the cancer cells. The IC50 doses determined by MTT assay showed the greater activity of DOX-NPs over free doxorubicin. Free doxorubicin was accumulated inside the MCF-7 cells as quickly as 3 hours. In contrast, DOX fluorescence from DOX-NPs in MCF-7 cells was observed after 6 hours of incubation. The results demonstrated that greater amount of free DOX and DOX-NPs were internalized in term of time dependent. Consequently, the efficacy of DOX loaded micelles was improved noticeably, owing to higher drug accumulation at the intracellular action site. O-Succinyl chitosan graft Pluronic® F127 copolymer nanoparticles have proven their potential to be used as anti-cancer drug carriers.

Index Terms—Core-Shell nanoparticles, Chitosan, Pluronic, and Doxorubicin.

Parichart Naruphontjirakul is with the Biological Engineering Program, King Mongkut’s University of Technology Thonburi, 126,Pracha-u-thit, Toong-kru Bangkok 10140, Thailand. (email: sung843@hotmail.com)
Kwanchanok Viravaidya-Pasuwat is with Department of Chemical Engineering, King Mongkut’s University of Technology Thonburi, 126, Pracha-u-thit,Toong-kru Bangkok 10140, Thailand. (Phone: +66 2 4709222, ext. 205; fax: +66 2 4709222; e-mail: kwanchanok.vir@kmutt.ac.th).

Cite: Parichart Naruphontjirakul and Kwanchanok Viravaidya-Pasuwat, "Development of Doxorubicin – Core Shell O-succinyl Chitosan Graft Pluronic®127 Copolymer Nanoparticles to Treat Human Cancer," International Journal of Bioscience, Biochemistry and Bioinformatics vol. 1, no. 2, pp. 131-136, 2011.