It is of crucial importance to modify chitosan‐based polysaccharides in the designing of biomedical materials. In this work, atom transfer radical poly­merization (ATRP) was employed to functionalize chitosan in a well‐controlled manner. A series of new degradable cationic polymers (termed as PDCS) composed of biocompatible chitosan backbones and poly((2‐dimethyl amino)ethyl methacrylate) (P(DMAEMA)) side chains of different length were designed as highly efficient gene vectors via ATRP. These vectors, termed as PDCS, exhibited good ability to condense plasmid DNA (pDNA) into nanoparticles with positive charge at nitrogen/phosphorus (N/P) ratios of 4 or higher. All PDCS vectors could well protect the condensed DNA from enzymatic degradation by DNase I and they displayed high level of transfectivity in both COS7, HEK293 and HepG2 cell lines. Most importantly, in comparison with high‐molecular‐weight P(DMAEMA) and ‘gold‐standard’ PEI (25 kDa), the PDCS vectors showed considerable buffering capacity in the pH range of 7.4 to 5, and were capable of mediating much more efficient gene transfection at low N/P ratios. At their own optimal N/P ratios for trasnsfection, the PDCS/pDNA complexes showed much lower cytotoxicity. All the PDCS vectors were readily to be degradable in the presence of lysozyme at physiological conditions in vitro. These well‐defined PDCS polymers have great potentials as efficient gene vectors in future gene therapy.

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In this paper, we demonstrate a simple and practical method to prepare chemically crosslinked gelatinbased hydrogels using b-cyclodextrin (b-CD) that plays a dual role as a crosslinker as well as a host molecule for enhanced binding of anticancer drug methotrexate (MTX), to achieve high drug loading level as well as controlled and sustained release of the anticancer drug. For this purpose, a series of novel b-CD-crosslinked gelatin-based hydrogels were synthesized and characterized. The b-CD content of the hydrogels was 11-15%, and the crosslinking degree was 21-36%. The gelatin-based hydrogels could swell well in PBS buffer. The hydrogels degraded hydrolytically and the degradation was accelerated by collagenase in PBS buffer. It was found that the higher water content resulted in faster biodegradation of the hydrogels regardless of the crosslinker used. Pyrene was used as a fluorescence probe to investigate the micro-environment of the gelatin-based hydrogels. Pyrene was well adsorbed in the b-CD-crosslinked hydrogels, and the pyrene molecules in the hydrogels were included and complexed within the hydrophobic cavities of the b-CD crosslinkers. The adsorption, loading, binding and complexation, and release of MTX in or from the hydrogels were investigated. MTX was adsorbed and loaded into the hydrogels by immersing the swollen hydrogel samples in MTX saturated aqueous solution. The loading of MTX in the hydrogels was confirmed by measuring the UV-vis spectra of the MTX-loaded hydrogels, the spectra indicated that the loaded MTX was complexed by b-CD in the b-CD-crosslinked hydrogels. Our data showed that the complexation of MTX with b-CD crosslinkers largely increased the loading level of MTX in the hydrogels. The complexation could also reduce the initial burst release effect, and then retard the release of the complexed MTX for a certain period, until the hydrogels started to hydrolytically degrade and all remained MTX was released. Due to the unique structures and properties, the b-CD-crosslinked gelatin-based hydrogels demonstrated an interesting multiphasic profile for controlled and sustained release of the MTX drug. Thus, the b-CD-crosslinked gelatin-based hydrogels may be utilized as a promising drug carrier for controlled and sustained release and localized delivery of anticancer drugs.