Multiscale Drug Delivery System: Micelles Encapsulated in Hydrogels

Micelles have been used in the drug delivery field for the encapsulation of active pharmaceutical ingredients in order to gain such advantages as extending overall drug circulation time in the body as well as well as solubilization of hydrophobic drugs. However, there are severe drawbacks to using micelles alone such as rapid disassembly when diluted below the critical micelle concentration. Hydrogels are hydrophilic networks of polymer chains which having been used clinically as implantable depots, but hydrogels are limited by rapid release of small molecule therapeutics. By encapsulating micelles in the hydrogel, we proposed to better control and extend drug release at the treatment site. The overall objective of this dissertation was to test the hypothesis that whole, intact micelles are released from hydrogels following encapsulation. Hydrogel mesh size, drug hydrophobicity, and micelle size were varied by controlling polymer molecular weight and drug type used. We discovered that the more hydrophobic the drug, the slower the rate of drug release from the hydrogel/micelle system following Higuchi's Model. A higher molecular weight macromer created hydrogels of larger mesh size and these hydrogels released drug-loaded micelles at a faster rate than hydrogels obtained from lower molecular weight polymer. When micelles were below the mesh size of the hydrogels, intact micelles could be released, as established using fluorescent techniques. When micelles were larger than the mesh of the hydrogel, free drug was confirmed to be released from the hydrogels. To summarize, this is the first time the mechanism of drug-loaded micelle release from hydrogel have been studied. Our results show a promising future not only for this system alone but for all devices capable of releasing micelles.