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Modulating insulin-release profile from pH/thermosensitive polymeric beads through polymer molecular weight
C Ramkissoon-Ganorkar1, F Liu, M Baudys
1Department of Pharmaceutics and Pharmaceutical Chemistry, Center for Controlled Chemical Delivery, University of Utah, Salt Lake City, UT 84112, USA.
Summary
Stimuli-sensitive polymer beads with varying molecular weights were developed to control insulin release. Lower molecular weight beads offer rapid release, while higher molecular weight beads provide sustained release for targeted drug delivery.
Area of Science:
- Polymer chemistry and materials science
- Biomaterials for drug delivery
- Protein therapeutics
Background:
- Developing stimuli-responsive materials for controlled drug release is crucial for improving therapeutic efficacy.
- Protein drugs require specialized delivery systems to maintain stability and achieve targeted release.
- Terpolymers combining temperature and pH sensitivity offer tunable properties for complex biological environments.
Purpose of the Study:
- To synthesize and characterize stimuli-sensitive terpolymers for controlled protein drug delivery.
- To investigate the effect of polymer molecular weight on insulin loading and release kinetics.
- To evaluate the potential of these polymeric beads for targeted delivery of protein drugs to specific gastrointestinal regions.
Main Methods:
- Synthesis of N-isopropylacrylamide (NIPAAm), butyl methacrylate (BMA), and acrylic acid (AA) terpolymers with controlled molecular weights.
- Preparation of pH/thermosensitive polymeric beads encapsulating insulin using a specific loading procedure at low pH and temperature.
- In vitro release studies of insulin from beads of varying molecular weights at different pH values (2.0 and 7.4) and 37°C.
Main Results:
- High insulin loading efficiency (90-95%) was achieved while maintaining protein stability.
- Negligible insulin loss at pH 2.0, indicating no burst release.
- Insulin release at pH 7.4 was dependent on polymer molecular weight: low MW beads released insulin within 2 hours, intermediate MW within 4 hours, and high MW over 8 hours.
- Release mechanisms transitioned from polymer dissolution (low MW) to swelling and diffusion (high MW).
- Loaded and released insulin retained full bioactivity.
Conclusions:
- Molecular weight of stimuli-sensitive terpolymers is a critical parameter for controlling protein drug release rates.
- Low MW beads are suitable for immediate release in the duodenum.
- Intermediate and high MW beads show potential for targeted delivery to the lower small intestine and colon, respectively.