: Natural polymers, particularly polysaccharide, have been used as drug delivery systems for a variety of therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and non-parenteral administration. Chitosan, the second most abundant naturally occurring polysaccharide after cellulose, is a biocompatible and biodegradable mucoadhesive polymer that is extensively used in preparation of nanoparticles (NPs). Chitosan NPs loaded with drugs were found to be stable, permeable and bioactive. In this review, the importance of chitosan and its derivatives in drug delivery are illustrated, different methods of preparation of chitosan and chitosan derivatives NPs and their physio-chemical properties are addressed. Moreover, the desirable characteristics for successful NPs based drug delivery systems as well as the pharmaceutical applications of these NPs are also clearly explored.

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Purpose: The aim is to develop a novel pH-responsive modified chitosan-based nanoparticles system for active loading of doxorubicin (DOX) and triggered intracellular release. Methods: Nanoparticles were formed in an aqueous medium via ionic interaction between negatively charged chitosan derivative and positively charged DOX at neutral pH, and then transformed in situ into cisplatin (CIS) cross-linked nanoparticles through cross-linking the formed micelles via chelation interaction between the negatively charged polymeric carrier and cisplatin. Nanoparticles were characterized in terms of particle size and zeta potential using DLS and TEM. Drug loading efficiency and encapsulation efficiency were determined based on the physio-chemical proprieties of the polymer and the amount of the cross-linking agent. In vitro release studies were performed using the dialysis method at different pHs. Finally, the cytotoxic effects of these nanoparticles were performed against the MCF-7 BrCA cell line under different pHs. Results: The average particle size of polymer alone and DOX nanoparticles was 277.401 ± 13.50 nm, and 290.20 ± 17.43 nm, respectively. The zeta potential was -14.6 ± 1.02 mV and -13.2 ± 0.55 mV, respectively, with a low polydispersity index. Drug loading and encapsulation deficiencies were determined, which were dependent on the amount of the cross-linking agent. In vitro release studies showed that the release of DOX from these nanoparticles was pH dependent. Moreover, results showed that the cytotoxicity magnitude of DOX-loaded nanoparticles against MCF-7 BrCA cells was higher compared with free DOX. Conclusion: These novel pH sensitive nanoparticles proved to be a promising Nano- drug delivery for tumor-targeted delivery of DOX.