Date of Award
M.S. in Pharmaceutical Science
Pharmaceutics and Drug Delivery
Parasitic diseases are a severe threat to people and animals. Praziquantel is the most common anti-parasitic drug with high efficiency, and it has been used to treat parasitic diseases for many years. However, it has very strong gastrointestinal and liver metabolism that leads to a strong first-pass effect and a short half-life. Additionally, the frequent oral administration was inconvenient for the large livestock. To overcome these drawbacks, this study aimed to develop an extended-release thermosensitive hydrogel formulation that was applicable to the injectable administration. The praziquantel-loaded hydrogel formulation based on poloxamer 407 (20%, w/v) was prepared, and two strategies for modifications of poloxamer 407 hydrogel were studied. One of them was the formulation consisting of PEG-DSPE/TPGS mixed micelles-poloxamer 407 hydrogel hybrid system; another was the poloxamer 407 hydrogel adding with HPMC as an adhesive. These hydrogel formulations had a reversible sol-gel transition property at approximate 26 °C and obtained high loading efficiencies and storage stability. in-vitro release studies, as well as in-vivo pharmacokinetic studies, were conducted to evaluate the extended-release effect, and the bioavailability of several optimized formulations of praziquantel was calculated. The in-vitro release of praziquantel was prolonged when loading into poloxamer 407 hydrogel. Both the modifications of poloxamer 407 hydrogel, by adding HPMC as well as utilizing PEG- DSPE/TPGS mixed micelle as a secondary delivery vehicle obtained the relatively better extended-release profiles than the original poloxamer 407 hydrogel. The pharmacokinetic studies indicated that the poloxamer 407 hydrogel formulation has a relatively high bioavailability and prolonged release profile, but both two modifications failed to obtain a significant improvement of an extended-release characteristic compared with the original hydrogel solution.
Feng, Sheng, "Design of Thermosensitive Hydrogel for Extended-Release of Praziquantel" (2019). Electronic Theses and Dissertations. 1593.