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Design of PLGA-Based Drug Delivery Systems Using a Physically-Based Sustained Release Model.
Stijn H S Koshari1, Xutao Shi1, Linda Jiang2
1Department of Chemical and Biomolecular Engineering, University of Delaware, Newark, Delaware 19716, USA.
Journal of Pharmaceutical Sciences
|September 13, 2021
Summary
This study advances controlled drug release design using an improved polymer degradation model. The model accurately predicts drug release from PLGA systems, identifying key factors influencing early-stage release.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Pharmaceutical Engineering
Background:
- Controlled drug release systems are crucial for therapeutic efficacy.
- Poly(lactic-co-glycolic) acid (PLGA) is widely used in drug delivery due to its biodegradability.
- Accurate modeling of drug release kinetics is essential for a priori design.
Purpose of the Study:
- To develop and validate an improved drug release model incorporating hydrolytic polymer degradation.
- To enable model-informed design of controlled drug release from PLGA systems.
- To investigate factors influencing early-phase drug release in PLGA rods.
Main Methods:
- Development of an extensive dataset for model validation.
- Mechanistic modeling of hydrolytic polymer degradation.
- Formulation of PLGA rods with FITC-dextran as a drug surrogate.
- In vitro release experiments and fluorescence microscopy analysis.
Main Results:
- The improved model accurately predicted drug release for various PLGA formulations.
- Discrepancies in early-phase release were linked to drug percolation and rod swelling/pore formation.
- Model parameter adaptation, not physical process modification, achieved accurate data fitting.
Conclusions:
- The model facilitates a priori design of controlled drug release from PLGA systems.
- Understanding polymer swelling and pore formation is critical for optimizing drug delivery.
- Careful selection of PLGA polymer grade is important for predictable drug release profiles.
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