University of Illinois at Chicago
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Protein-Polymer Interactions Influence on the Stability of Polymeric Micelle Formulations

thesis
posted on 2022-12-01, 00:00 authored by Catherine F Dial
In this study, the effect of protein-polymer interactions on stability of micelle formulation stability was determined. The interactions between serum albumin and methoxy-poly(ethylene glycol-block-ε-caprolactone) (mPEG-CL) and methoxy-poly(ethylene glycol-block-lactide) (mPEG-LA) were characterized. Micelle formulation stability was assessed by determining micelle kinetic stability (unimer exchange), micelle disassembly, cargo loss from the micelle, and cargo exchange, or leakiness, between micelles in the absence or presence of serum albumin. Finally, micelle disassembly and cargo loss was also determined in the presence of lipoproteins. Overall, it was determined that micelle stability does not correlate with protein-polymer interactions. The mechanisms of instability were dependent on material. The primary mechanism of micelle instability was due extraction of cargo from the micelles by serum lipoproteins. Because extraction by lipoproteins occurred faster than typical cargo exchange, it was concluded that lipoproteins disrupt micelle encapsulation and extract the cargo, rather than simply absorbing released cargo from the micelles. Better understanding of mechanisms of micelle instability provided by this study will aid in directing new micelle formulation development and improving therapeutic efficacy.

History

Advisor

Gemeinhart, Richard A

Chair

Gemeinhart, Richard A

Department

Pharmaceutical Sciences

Degree Grantor

University of Illinois at Chicago

Degree Level

  • Doctoral

Degree name

PhD, Doctor of Philosophy

Committee Member

Cheng, Gang Gao, Yu Lee, Seung-Young Li, Tonglei

Submitted date

December 2022

Thesis type

application/pdf

Language

  • en

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