Synthesis of N-vinylcaprolactam and methacrylic acid based hydrogels and investigation of drug release characteristics

In this study, N-vinylcaprolactam (VCL) and methacrylic acid (MAA) based copolymeric hydrogels with different VCL/MAA molar ratios were produced to develop a temperature-sensitive biomaterial for use in drug delivery systems. For this purpose, poly(N-vinylcaprolactam-co-methacrylic acid) hydrogels, symbolized p(VCL-co-MAA) were synthesized by free radical polymerization in an ethanol medium using different monomer ratios at 70 degrees C with 2,2 '-azobis(2-methylpropionamidine) dihydrochloride (AMPA) as an initiator, and in the presence of crosslinking agent (N,N '-methylenebisacrylamide). The structures of hydrogels were confirmed by Fourier Transform Infrared Spectroscopy (FTIR). The addition of MAA, which has an ionizable group as a comonomer to the structure, it also provided pH sensitivity to VCL based hydrogels as well as its temperature sensitivity. In order to examine the drug release properties, first, the swelling-shrinking behaviors of these hydrogels were determined in the temperature range of 25-60 degrees C and different pH values (2.1, 5.5, and 7.2) in equilibrium time (24 h). Then, the drug release profiles of these hydrogels were assessed in in vitro conditions at 37 degrees C and different pH values using mimic biological fluids for Rhodamine B (Rh B), a cationic model drug. The maximum drug release values were founded in the range of 34-57%, 73-90%, 69-76% at pH 2.1, 5.5, and 7.2, respectively, for the hydrogels with different VCL/MAA molar ratios. At the end of the swelling and drug release experiments, it was seen that the swelling degree of synthesized hydrogel exhibited to both dependent temperature and pH. Furthermore, it was observed that the amount% of the drug and the rate of drug release also changed depending on the change in pH values. In addition, surface morphologies of hydrogels were examined by Scanning Electron Microscopy (SEM) before and after drug release. Then, the kinetic mechanism of the drug release behavior of hydrogels was investigated using zero-order, first-order, Higuchi, and Korsmeyer-Peppas models for all three pH values. The kinetic release profile of the p(VCL-co-MAA) hydrogel was determined to fit into the Higuchi model, generally. Although, the correlation coefficients showed that the hydrogel fitted to the Higuchi model at all pH conditions, analysis with the Korsmeyer-Peppas equation had been assisted more precisely in the understanding of one or more than one mechanisms controlling the release, at different pH values. According to the kinetic release modeling results, it may be concluded that swelling and diffusion processes were probably simultaneously effective on the drug release mechanism. All these results imply that prepared dual-responsive p(VCL-co-MAA) hydrogels may be used for potential applications such as long-term controlled drug release systems like 24 h in the gastrointestinal system with varying pH values.

Automated summary

In this study, copolymeric hydrogels based on N-vinylcaprolactam (VCL) and methacrylic acid (MAA) were synthesized to develop a temperature-sensitive and pH-sensitive biomaterial for drug delivery systems. The drug release properties of the hydrogels were investigated, and it was found that the hydrogels showed potential for long-term controlled drug release systems with varying pH values.