Targeted drug delivery system:- formulation and evaluation of chitosan nanospheres containing doxorubicin hydrochloride

Sokkalingam Arumugam Dhanaraj, Muralidharan Selvadurai, Kumaraswamy Santhi, Amanda Lim Sze Hui, Cheong Jia Wen, Hoh Chew Teng

Abstract


A chitosan molecule form self-assembled nanoparticles that can encapsulate a quantity of drugs and deliver them to a specific site. Chemical attachment of drug to chitosan throughout the functional linker has possibility to produce useful prodrugs, exhibiting biological activity at target site. In vivo residence time of the dosage form in the gastrointestinal tract and bioavailability of various drugs increases by mucoadhesive and absorption enhancement properties of chitosan. Antitumour activity of doxorubicin(DOX)-incorporated nanoparticles in vitro on DOX- resistant C6 glioma cells. Nanoparticles showed increased cytotoxicity compared to DOX alone. These results suggest that doxorubicin (DOX) was unable to penetrate into cells and did not effectively inhibit cell proliferation. In contrast, nanoparticles can penetrate into cells and effectively inhibit cell proliferation.

There are 3 batches of drug loaded nanospheres in which 2.5mg,5mg and 10mg of DOX were loaded into nanospheres where the concentration of chitosan is 1%w/v. Anticancer drugs without targeting a specific site cause side effects. The objective of this research is to reduce side effects. HPLC device was used to quantitatively analyze amount of doxorubicin loaded in nanospheres. The result had showed concentration of anticancer drug loaded in nanospheres is directly proportional to the drug payload capacity until saturation point. The in vitro drug release studies was carried out for 48 hours to obtain a more precise result by carrying out this studies in a medium resembling our body environment such as pH7.4, 37ºC with analytical grade water for this studies.

In vitro release of doxorubicin is of zero order kinetic. This shows that release is independent of the concentration of drug loaded in the nanospheres. Besides that, the graphs also show a sustained release manner, indicating these nanospheres formulation are suitable for targeting drug delivery system and for efficient treatment of cancerous cells.

Keywords


chitosan; naoparticles; doxorubicin; cytotoxicity; targeting

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