Date of Award
M.S. in Pharmaceutical Science
Pharmaceutics and Drug Delivery
An increasing number of protein drugs are used in the clinic to treat a broad range of diseases. However, because of their large molecular sizes and high hydrophilicity, protein drugs are not orally bioavailable, which commonly require intravenous, intramuscular or subcutaneous injection. Thermosensitive polymers have been widely investigated as in situ depots for sustained drug release delivered through subcutaneous route.Albumin is the most abundant proteins in bloodstream. It has long half-life (19 days in human) and plays important roles such as acting as carrier for fatty acids, amino acids, waste products and medical compounds. Albumin has been studied for decades as a drug delivery vehicle but due to highly species dependent of FcRn, the receptor responsible for circulating albumin, the efficiency of human albumin therapeutics reduced in rodent models in preclinical development of pharmaceutical products. In this study, 30% (w/v) P407 hydrogel was used to deliver mouse serum albumin (MSA) and human serum albumin (HSA) subcutaneously. In vitro studies showed that the drug release from gel formulation mainly depended on gel erosion and was species independent. Despite of having different binding affinity to murine FcRn, albumin from both species had similar bioavailability and area under the curve for gel formulation and free drug solution administered through subcutaneous route. In comparison to MSA and HSA, in recent research, BSA delivered in mice had higher maximum plasma concentration delivered in IV route. Furthermore, the in vivo imaging showed that most of MSA and HSA were absorbed over time while BSA got trapped at the injection site. This leaded to the conclusion that though pharmacokinetic parameters of albumin-Cy5.5 SC injections were similar to each other, the reasons for the similarity were different. For BSA-Cy5.5, it was because of slow absorption while for MSA-Cy5.5 and HSA-Cy5.5, it was because of fast distribution of the drugs to organs. Furthermore, half-life of human serum albumin in mice was shorter than half-life of MSA and it was much shorter comparing to that in human (19 days) because mouse FcRn has higher binding affinity for mouse serum albumin than human serum albumin.
Nguyen, Vy, "Subcutaneous Delivery of Albumin" (2021). Electronic Theses and Dissertations. 2036.
Available for download on Sunday, June 04, 2023