Studies On Swelling Kinetics Theory And Drug Release Kinetis Of Environmental Sensitive Hydrogels

In this paper, we studied two series of environment-sensitive hydrogels. Firstly,pH-sensitive hydrogels P(SA-g-AA) were synthesized by graft cross-link copolymer-izeation of sodium alginate (SA) and acrylic acid (AA) using N, N-methylene-bis-(acrylamide) as a cross-linker. Secondly, pH and thermo-sensitive hydrogelsP(NIPAAm-co-MAA) were synthesized by N-isopropylacrylamide(NIPAAm),methacrylic acid(MAA) using 4,4'-diamino-azobenzene(DMAAB) as a cross-linker.Hydrogels of P(SA-g-AA) have a good pH-sensitivity. The swelling kinetics ofthe hydrogels in pH≤4.0 buffer solutions showed an overshooting effect, which wasinterpreted on a cooperative physical cross-linking caused by the hydrogen bondformation between the carboxyl groups of the hydrogels during swelling processes.The overshoot processes of the hydrogels under ph≤4.0 medium follow aquantitative model proposed by Diez-Pena. E et al; Overshoot phenomenon did notappear in pH≥5.0 buffer solutions and their swelling processes follow Schott'ssecond-order rate equation. Deswelling kinetics of hydrogels can be divided twodifferent cases. On one hand hydrogels were swollen to equilibrium at pH7.0 buffersolution then transferred into acidic buffer solutions, on the other hand hydrogelswere swollen to equilibrium in deionized water then transferred into acidic buffersolutions. Deswelling processes of the former revealed two different cases: swollenhydrogels deswelled immediately after they were immersed into pH2.2-3.0 buffersolutions, but there was a short time swelling before deswelling after their immersioninto the pH4.0-6.0 buffer solutions which were attributed to carboxylic ions in thenetworks were screened by sodium ions. We proposed a deswelling kinetics modelbased on ionic screen theory about above two cases. There was a good accordancebetween experimental results and academic curves. For hydrogels swollen indeionized water, all processes of deswelling in pH4.0-5.0 buffer solutions did notexhibit a short time swelling before deswelling but a direct deswelling becausecarboxylic ions in the networks were not screened by sodium ions. In this casedeswelling processes of the gels follow a quantitative second deswelling kineticsmodel. Release efficiency of gels in pH7.4 buffer solution is higher than in pH2.0buffer solution. Drug release processes of hydrogels in pH2.0 and pH7.4 buffersolution can be described by Ritger-Peppa model and diffuse-relaxation modelrespectively.P(NIPAAm-co-MAA) hydrogels have a excellent pH and thermo-sensitivity.The swelling behavior of the hydrogels in pH7.0 buffer solution after previouslysoaked under acidic medium revealed an autocatalytic swelling kinetics, which wasdue to the formation of crossed-linked hydrogen bonds during immersed in acidicmedium. This anomalous swelling process was in accordance with autocatalyticmodel proposed by Diez-Pena. E et al. The overshoot effect was also observed duringthe swelling process in acidic medium after protreated in pH7.0 buffer solution ofhydrogels, which was due to formation of cooperative physical cross-linking causedby hydrogen bonds between amido and protonated carboxyl groups. The phenomenaof deswelling processes of P(NIPAAm-co-MAA) swollen to equilibrium in buffer solution was similar to P(SA-g-AA) at the same study condition. After drug loadingin in dimethylformamide (DMF), drug release processes of P(NIPAAm-co-MAA)hydrogels in pH2.0 and pH7.4 buffer solutions accorded with Ritger-Peppa model andautocatalytic mechanism respectively. The swelling and drug release property anddegradability by azoreducase of P(NIPAAm-co-MAA) can be designed as a drugcarrier for oral colon-specific drug delivery system.