Stimuli-responsive hydrogels for drug delivery obtained by radiation copolymerization

Preparation and characterization of different smart hydrogels were prepared for drug delivery systems by using gamma irradiation. The factors affecting the preparation and homogeneity of prepared hydrogels were thoroughly investigated. pH-sensitive hydrogels were prepared by radiation copolymerization of methacrylic acid (MAAc)/ Butyl acrylate (BA) and ketoprofene was used as a drug model. BA/MAAc copolymer gels showed a good sensitivity to pH. The aqueous equilibrium swelling properties of these copolymers were investigated. It was found that the percent swelling for copolymers prepared in acetone is higher than that prepared in other solvents at different pH's. However, the percent swelling of the copolymer prepared in ethanol or ethanol /water is very low at lower pH's. Therefore, the suitable solvent to meet the required properties for drug delivery to colon is ethanol and its mixture with water. The effect of water/ethanol composition on the swelling behavior was also studied to find out that the maximum swelling is obtained at (40/60 wt%). The extent of the transition from the collapsed hydrophobic state to hydrophilic one is depending on comonomer compositions. The release of ketoprofene -loaded during radiation process- under different pH's from gel was determined. it was found that at pH 7, the release of ketoprofene increases as its concentration in the gel increases, but it decreases with increasing irradiation dose. However, at pH 1 the release of drug has no significant value. The release of loaded ketoprofene that immersed in the copolymer after irradiation was found to be much higher than that released from gel loaded drug during irradiation process. Swelling of (MAAc/ BA) copolymer is a highly pH dependent, at low pH the swelling is less than 10%, but at high pH is higher than 300%. This property candidate such copolymer to be pH-sensitive hydrogel for the use in drug-delivery systems. Intelligent hydrogels capable of swelling or collapsing in water below or above their low critical solution temperature (LCST), respectively, by γ- rays copolymerization of poly(vinyl alcohol), PVA, and N-isopropyl acrylamide (NIPAAm) were also prepared. Terpolymer hydrogels composed of PVA, NIPAAm and different pH-sensitive polymers such as acrylic acid (AAc), MAAc acid and N-N dimethyl aminoethyl methacrylate (DMAEMA) were prepared. The equilibrium swelling for the prepared different terpolymers was thoroughly investigated at various pHs. The hydrophilicity of NIPAAm and other pH-sensitive comonomer greatly influence the critical collapse pH- of the terpolymer. By altering the copolymer composition, LCST can be controlled. The content of NIPAAm in the copolymer control and enabled the transition temperature to be easily shifted up and down. Also, it was found that the maximum swelling is obtained at pH 1 for all terpolymers investigated and its extent is depending on the composition of the hydrogel. In general, the prepared hydrogels are of great interest for possible practical uses as stimuli-responsive hydrogels for drug delivery systems under controlled release in specific sites. (author)