Abstract

A chitosan-alginate nanoparticle system encapsulating doxorubicin (DOX) was prepared by a novel ionic gelation method using alginate as the crosslinker. These nanoparticles were around 100 nm in size and more stable with higher positive zeta potential and had higher % encapsulation efficiency (95%) than DOX loaded chitosan nanoparticles (DOX Csn NP) crosslinked with sodium tripolyphosphate (STPP). FTIR spectroscopy and thermogravimetric analysis revealed successful loading of DOX.In vitrodrug release showed an initial release phase followed by slow release phase with higher cumulative release obtained with DOX loaded chitosan-alginate nanoparticles (DOX Csn-Alg NP). Thein vitrocytotoxicity of DOX released from the two nanoparticle systems showed a notable difference on comparison with that of free DOX on the MCF-7 cell line. The SRB assay, AO/EB staining, and fluorescence uptake study indicated that free DOX only showed dose dependent cytotoxicity, whereas both dose and time dependency were exhibited by the two sets of NPs. While both systems show sustained release of DOX, from the cell viability plots, DOX Csn-Alg NPs showed their superiority over DOX Csn NPs. The results obtained are useful for developing DOX Csn-Alg NPs as a sustained release carrier system for DOX.

Highlights

  • Doxorubicin (DOX), with the trade name Adriamycin known as hydroxydaunorubicin and hydroxydaunomycin, is a drug used in cancer chemotherapy and derived by chemical semisynthesis from a bacterial species [1]

  • The chitosan NPs are formed by the gelation with sodium tripolyphosphate (STPP) via electrostatic interactions

  • In aqueous solutions with pH around 5.2 chitosan amino groups interacted with alginate carboxylate groups to form the hydrogel

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Summary

Introduction

Doxorubicin (DOX), with the trade name Adriamycin known as hydroxydaunorubicin and hydroxydaunomycin, is a drug used in cancer chemotherapy and derived by chemical semisynthesis from a bacterial species [1]. In order to increase the anticancer efficacy by prolonging the circulation time in blood stream and reduce its toxicity, different carrier systems for DOX have been developed such as liposomes [4] and polymeric nanoparticles [5]. The primary goal of using nanotechnology in medicine is to develop new safety delivery systems having reduced toxicity and biocompatibility while maintaining therapeutic effects [6]. It has become customary to use naturally occurring polymers as source materials for drug delivery [7].

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