Development of hydroxypropyl cellulose-filled poly(2-hydroxyethyl methacrylate) semi-interpenetrating networks for drug delivery
Cancer is the second leading cause of death in the United States of America and the National Cancer Institute has released a paper stating that the ideal cancer therapy should have an imaging, targeting, reporting, and therapeutic part. The overall project goal is to be able to create a delivery system that can be triggered externally to the body and can release an anticancer agent in a controlled manner. The current project deals specifically with using hydroxypropyl cellulose (HPC) filled poly(2-hydroxyethyl methacrylate) (PHEMA) (HFPG) hydrogel to cause a release of theophylline when the hydrogel is placed at a temperature above the lower critical solution temperature (LCST) of HPC (57 ºC) and to have no release at normal body temperature, 37 ºC. In a series of polymerization reactions, various compositions of hydroxypropyl cellulose (HPC) filled crosslinked PHEMA gels were synthesized by free radical polymerization. The LCST for different average molecular weights, M̅_n, of HPC were found to be 44.8 ºC ± 0.8, 48.7 ºC ± 0.3, and 46.2 ºC ± 0.7 for 80,000, 100,000, and 370,000 M̅_n HPC respectively. A change in concentration of HPC with a M̅_n 80,000 from 0.01 to 0.05 g/mL showed an increase in the LCST from 44.8 ºC ± 0.8 to 46.6 ºC ± 1.0. Changing the media from water to 0.65M sodium chloride change LCST from 46.6 ºC ± 1.0 to 35.4 ºC ± 2.3. The swelling study showed the mesh size was unaffected by synthesis temperature, analytical temperature, and HEMA to HPC ratio, indicating that HPC was pore-filling. Mechanical testing confirmed the results of the swelling study, in that there was no net change in the calculated mesh size with a change in analytical or synthesis temperature by either method. This study showed that HPC did change the mesh size with a change in the HEMA:HPC ratio. Dissolution testing for the release of theophylline from the HFPG hydrogel showed an increased release rate with an increase in analytical temperature was possible. The increase in synthesis temperature increased the release rate. It is shown that an increase in the HEMA:HPC ratio with a decrease in the diffusion coefficient. The HPC collapsed and evolved out of the HFPG and this effect could produce a higher diffusion. Further investigations should be conducted to test the effects of different initiators and crosslinking ratio's on the release of HFPG hydrogels.