Synthesis and characterization of PnVCL grafted agar with potential temperature-sensitive delivery of Doxorubicin

Thermo-responsive copolymer, Agar agar-graft-poly(N-vinylcaproactam) (AA-g-PnVCL) was prepared by grafting N-vinylcaprolactam units onto the Agar backbone. Graft copolymer was synthesized by free-radical polymerization, using 2,2 '-Azobis(2,4-dimethylvaleronitrile) (AMVN) as an initiator in the nitrogen atmosphere. In order to evaluate the composition effect different ratios between Agar agar, nVCL and AMVN were used. The formation of AA-g-PnVCL was confirmed by FT-IR, TGA, 1H NMR, and XRD techniques. Viscosity average molecular weight (M eta over line ) was determined after the measurement of intrinsic viscosity. Turbidity measurements of dilute aqueous solutions were used to determine the lower critical solution temperature (LCST) of the new polymer. The grafting was evaluated by estimation of the percentage of grafting, grafting efficiency and percentage of conversion. One of the prepared polymer models (dried powder Model 4 with AA/VCL ratio 1:20 and VCL/AMVN ratio 20:1) showed the desired temperature-sensitive behavior (LCST 40 degrees C) and was further characterized. Its swelling was investigated with the determination of swelling indices in different media and at different temperatures. SEM images of dried and lyophilized gels were taken in order to investigate the morphology of the systems. Viscous and elastic moduli were determined at different temperatures for gel characterization. Doxorubicin (Dox) was chosen as a model drug and it was formulated into an injectable gel drug delivery system. Its loading and in vitro drug release was studied. The cytotoxicity of the proposed Dox loaded Model 4 was further characterized by the MTT test on H9c2 cardio blasts. The results showed successful preparation of a new temperature-sensitive polymer AA-g-PnVCL. Model 4 showed sufficient grafting efficiency and desired LCST for potential application as a modified drug delivery carrier. The proposed dosage form showed delayed release at 25 degrees and 37 degrees C and rapid release at 40 degrees C. These results suggest that AA-g-PnVCL could be a potential stimuli-responsive material for controlled drug delivery in tumor chemotherapy with reduced cardiotoxicity of Doxorubicin.