Targeted drug delivery is gaining success at recognizing diseased cells and sparing healthy cells from the toxic side effects of the drugs. A particularly important field for targeted drug delivery is chemotherapy, which can produce overwhelming side effects in cancer patients. To overcome the nonlocal character of chemotherapy, we have designed a package-within-a-package drug delivery system. The system consists of two components; the first is a non-ionic surfactant vesicle that is made up of a synthetic amphiphilic bilayer and cholesterol. The second is a biodegradable temperature and pH sensitive chitosan polymer hydrogel. The drug is first encapsulated in the vesicles which are then embedded in the hydrogel network.

The non-ionic vesicles were prepared by hydration of amphiphilic films with a PBS buffer solution and a fluorescent marker, 5,6-carboxyfluorescein. The marker molecule was introduced to mimic and test the release rate of a drug from the vesicle interior. After hydration, the vesicles were extruded to constrict their size distribution. Unentrapped dye was removed using two techniques: ultracentrifugation and gel filtration. The vesicles obtained by both methods were compared to determine which technique was better. Gel filtration resulted in excessively dilute solution of vesicles and was judged the less efficient method. The entrapment capability of the vesicles was measured by disrupting the vesicles with Triton X-100, and quantifying the fluorescent signal change before and after vesicle rupture. We then measured the release rate of the dye from intact vesicles when exposed to high ion and low ion environments. The dye encapsulated vesicles were placed in a semi-permeable cellulose membrane and immersed in a solution of either PBS or Milli-Q water. Readings were taken at different time intervals and the released dye concentration determined using fluorescence spectroscopy. The release rate was found to be higher in Milli-Q water than in PBS solution.

This result indicates that drug release from vesicles is highly dependent on ion concentration. To preserve the function of vesicles in different ionic environments, a hydrogel matrix can stabilize vesicles and lend precise control over drug release. This package-within-a-package drug delivery system will not only decrease toxicity to other parts of the body and provide double control over release rates but will also increase direct utilization of the drug resulting in safe and effective treatment of ovarian cancer patients.

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