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Micellized α-Cyclodextrin-Based Supramolecular Hydrogel Exhibiting pH-Responsive Sustained Release and Corresponding
Anis Abdul Karim1, Pei Lin Chee1, Meng Fai Chan2
1Institute of Materials Research and Engineering (IMRE), A*STAR (Agency for Science, Technology and Research), 2 Fusionopolis Way, Innovis, Singapore 138634.
Injectable supramolecular hydrogels made from PLLA/DMAEMA/PEGMA polymers and α-CD offer sustained protein release for 60-120 hours. pH-dependent rheology and network interactions control the release mechanism, combining diffusion and erosion.
Area of Science:
- Polymer Science and Engineering
- Biomaterials Science
- Drug Delivery Systems
Background:
- Supramolecular hydrogels offer tunable properties for controlled release applications.
- Injectable formulations are desirable for minimally invasive drug delivery.
- Poly(L-lactic acid) (PLLA), poly(2-(dimethylamino)ethyl methacrylate) (DMAEMA), and poly(poly(ethylene glycol) methyl ether acrylate) (PEGMA) are biocompatible polymers.
Purpose of the Study:
- To fabricate injectable supramolecular hydrogels for sustained protein release.
- To investigate the influence of pH on hydrogel properties and drug release kinetics.
- To elucidate the mechanisms governing protein release from the hydrogel network.
Main Methods:
- Fabrication of tricomponent hydrogels using PLLA/DMAEMA/PEGMA polymers and alpha-cyclodextrin (α-CD).
- Rheological analysis to assess hydrogel behavior under shear and varying pH.
- Protein release studies using Bovine Serum Albumin (BSA) and lysozyme at pH 3, 7, and 10.
- Analysis of release mechanisms using Lissajous-Bowditch curves and Power Law.
Main Results:
- The hydrogels sustained protein release for 60-120 hours.
- pH significantly influenced hydrogel rheology and protein release profiles.
- Protein release was governed by complex interactions including protein properties, polymer pKa, and hydrogel pore size.
- Lissajous-Bowditch curves revealed pH-dependent microstructural changes affecting network integrity.
- The release mechanism was a combination of diffusion and erosion (non-Fickian and super case II transport).
Conclusions:
- PLLA/DMAEMA/PEGMA/α-CD supramolecular hydrogels are effective for sustained protein delivery.
- pH is a critical parameter for controlling hydrogel network structure and drug release.
- Understanding the interplay between hydrogel properties and protein characteristics is key for optimizing drug delivery systems.
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