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Targeted oral release systems have been a large topic within drug delivery systems. There are several benefits to an oral delivery including patient convenience and lower chance of infection. The colon specifically has been researched as the release media. The colon is an ideal location for a release because the pH is stable with high levels of microorganisms. Like any type of drug delivery research, there are several hurdles to overcome. In order for a drug to be released in the colon, the drug must survive the stomach and be biocompatible. This biocompatibility and pH sensitivity was created using a polymerized hydrogel. The matrix is designed to be sensitive to low pH’s seen in the stomach and small intestines then swell and release the drug in the higher pH of the colon. The polymerized hydrogel in this research is created from a hydrophobic monomer phase and an aqueous surfactant phase. Further details of the structure can be found in the paper. This polymer hydrogel matrix has been optimized, but the chemical nature of the release is currently unknown. Up until this honors research project, it was assumed that the polymer hydrogel released the drug within a micelle, but there is no proof that this occurs. Validating that the polymer hydrogel releases surfactant as a micelle is important to future research. Micelles are small enough to pass into the blood stream without detection from the body. When micelles degrade, they release the drug that was encapsulated inside. The GI tract is simulated over the course of several buffers.
Micelles are generally detected by searching for the critical micelle concentration, CMC. Above the CMC, micelles form readily in solution. The CMC can be found through surface tension analysis. As the concentration of the surfactant increases, the surface tension starts to fall. A calibration curve of the concentration of the surfactant versus the surface tension was created for each buffer. Over the course of the release, the surface tension was measured. As the release progressed, the amount of surfactant released from the hydrogel increases and the surface tension decreases. Through previous experiments, it was predicted that surfactant micelles will be released from the hydrogel in the higher pH values. The polymerized hydrogel was designed to swell at the higher pH’s, thus releasing more drug into solution. At the higher concentrations of surfactant, it is more likely for micelles to form. Surface tension analysis will be used to prove this hypothesis.
After all experiments were completed and analyzed, the results showed that micelles were released into solution. At the higher pH buffers of 6.8 and 7.4, the CMC concentration was achieved around 4 hours in the 6.8 pH and around 26 hours in the 7.4 pH buffer at 25°C. Enough surfactant was released at the lower pH of 4.5 to also create micelles. The drugs were released from the polymer hydrogel at two different temperatures, room temperature and body temperature. The hydrogel that was released at body temperature released less surfactant in the lower pH’s of 2, 4.5, and 6.8. At the final pH of 7.4, the pH that simulates the colon, the release at the body temperatures was consistent and smooth.
The results of these experiments are promising for future experiments. In order to ensure these results are accurate, it is recommended that these experiments be rerun. Once this is done, the hydrogel can loaded with a drug to further study to the release. Once this release is completed the results of the blank hydrogel and loaded hydrogel can be compared.
Dr. H.M. Cheung
Dr. Bi-Min Newby
Dr. Gang Cheng
Emmert, Katie, "Determining the Critical Micelle Concentration of Polymer Matrix for Drug Delivery Purposes" (2015). Williams Honors College, Honors Research Projects. 12.