A Novel and Inexpensive Method Based on Modified Ionic Gelation for pH-responsive Controlled Drug Release of Homogeneously Distributed Chitosan Nanoparticles with a High Encapsulation Efficiency

Homogeneous chitosan nanoparticles utilizing EPR effect and pH-sensitive properties have an immense potential for loading and delivery of anticancer drugs. The aim of this study was preparing doxorubicin-loaded homogeneously distributed chitosan nanoparticles by using a simple and mild method, modified ionic gelation, with a very high encapsulation efficiency for controlled and pH-sensitive release. FESEM image revealed that the synthesized chitosan nanoparticles had a uniform spherical morphology with the size range 20-35 nm. The parameters of drug stirring duration, drug amount and nanoparticles formation time were changed to achieve maximum encapsulation efficiency as well as the effect of each parameter on the encapsulation efficiency was studied. The encapsulation efficiency toward doxorubicin under optimal conditions was 81.6 +/- 0.8 % (n=5 +/- SD) that was higher than those previously published in literature. The investigations of doxorubicin release from chitosan nanoparticles in four media with different pH values showed a pH-sensitive release with a higher release rate in an acidic environment. The drug release mechanism at all pH values was also evaluated by zero-order, first-order, Higuchi and Korsmeyer-Peppas models. The most consistent model for release curve at four pHs was Korsmeyer-Peppas model. Therefore, we presented a method for the preparation of homogeneous doxorubicin-loaded chitosan nanoparticles with small size that can be industrialized because they were made based on a very simple and green method without the use of a complex system and expensive materials as well as due to their high encapsulation efficiency.