Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies
| Autor: | Daniel G. Greene, Kaitlyn Wendl, Hyunsoo Park, Scott Sherman, Roman Shimanovich, Darren L. Reid, Prashant Agarwal, Leonela Vega |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Materials science
Hydrodynamic radius Pharmaceutical Science macromolecular substances 02 engineering and technology 030226 pharmacology & pharmacy Polyethylene Glycols 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine X-Ray Diffraction Scattering Small Angle chemistry.chemical_classification Small-angle X-ray scattering technology industry and agriculture Temperature Hydrogels Polymer 021001 nanoscience & nanotechnology PLGA Drug Liberation chemistry Chemical engineering Delayed-Action Preparations Self-healing hydrogels Drug delivery Lysozyme 0210 nano-technology Ethylene glycol |
| Zdroj: | European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 158 |
| ISSN: | 1879-0720 |
| Popis: | Sustained-release formulations are important tools to convert efficacious molecules into therapeutic products. Hydrogels enable the rapid assessment of sustained-release strategies, which are important during preclinical development where drug quantities are limited and fast turnaround times are the norm. Most research in hydrogel-based drug delivery has focused around synthesizing new materials and polymers, with limited focus on structural characterization, technology developability and implementation. Two commercially available thermosensitive hydrogel systems, comprised of block copolymers of poly(lactic-co-glycolic acid)-b-poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (PLGA) and poly(lactide-co-caprolactone)-b-poly(ethyleneglycol)-b-poly(lactide-co-caprolactone) (PLCL), were evaluated during this study. The two block copolymers described in the study were successfully formulated to form hydrogels which delayed the release of lysozyme (> 20 days) in vitro. Characterization of formulation attributes of the hydrogels like Tsol-gel temperature, complex viscosity and injection force showed that these systems are amenable to rapid implementation in preclinical studies. Understanding the structure of the gel network is critical to determine the factors controlling the release of therapeutics out of these gels. The structures were characterized via the gel mesh sizes, which were estimated using two orthogonal techniques: small angle X-ray scattering (SAXS) and rheology. The mesh sizes of these hydrogels were larger than the hydrodynamic radius (size) of lysozyme (drug), indicating that release through these gels is expected to be diffusive at all time scales rather than sub-diffusive. In vitro drug release experiments confirm that diffusion is the dominating mechanism for lysozyme release; with no contribution from degradation, erosion, relaxation, swelling of the polymer network or drug-polymer interactions. PLGA hydrogel was found to have a much higher complex viscosity than PLCL hydrogel, which correlates with the slower diffusivity and release of lysozyme seen from the PLGA hydrogel as compared to PLCL hydrogel. This is due to the increased frictional drag experienced by the lysozyme molecule in the PLGA hydrogel network, as described by the hydrodynamic theory. |
| Databáze: | OpenAIRE |
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