Date of Award
1-1-2022
Document Type
Dissertation
Degree Name
Ph.D. in Pharmaceutical Sciences
First Advisor
Michael Repka
Second Advisor
Chalet Tan
Third Advisor
Walter G. Chambliss
School
University of Mississippi
Relational Format
dissertation/thesis
Abstract
Protein therapeutics due to their high potency, high specificity, and desirable profile have gained a lot of traction in the last decade. Though the route of administration is limited to parenteral routes. There are also short half-life and instability issues observed in protein therapeutics making it necessary to develop delivery systems.
In the first chapter interleukin 15 as a cytokine was introduced while the second chapter talks more in detail about the development of a local depot hydrogel formulation for the delivery of recombinant interleukin 15. In vitro stability, and release studies were performed to select the optimum formulation for in vivo subcutaneous delivery to the mice. Thermosensitive hydrogel developed was capable of releasing rhIL-15 in the systemic circulation over a period of 5 days.
In the third chapter, liposomal formulations were prepared for the delivery of proteins to the lungs. The formulations were loaded with near-infrared labeled albumin. In vitro studies were performed to determine the optimal mol% of phospholipids used in the formulation and upon selection of the formulation in vivo studies were performed to analyze the pharmacokinetic parameters and monitor the distribution of formulation in mice via live imaging. The formulation was capable of delivering protein to the systemic circulation and was observed in the system for 240h. The formulation developed provides a promising approach for the delivery of protein therapeutics to systemic circulation from lung administration.
Recommended Citation
Ponkshe, Pranav, "Development of Local Depot Formulation for Sustained Systemic Delivery of Proteins" (2022). Electronic Theses and Dissertations. 2454.
https://egrove.olemiss.edu/etd/2454
Concentration/Emphasis
Pharmaceutics