PLGA-PEG-PLGA and PLCL-PEG-PLCL from PolySciTech used in development of Thermogel-based drug-delivery platform

 

Thermogels are a specific class of polymers which have the unique ability to transition from a liquid into a solid or semi-solid gel upon heating. These can potentially be used for delivery of delicate, large-molecule drugs such as proteins and enzymes. The advantage to this is that the formulations can be generated entirely in water which is an advantage over most other formulations such as microparticles and nanoparticles that require processing in an organic solvent that might damage the protein. Recently, researchers at Amgen, Inc. and Bristol Myers Squibb used PLGA-PEG-PLGA (AK097) and PLCL-PEG-PLCL (AK109) from PolySciTech (www.polyscitech.com) to develop test formulations to deliver the model enzyme lysozyme. This research holds promise to provide for novel protein-based drug delivery systems that could be applied for treating an array of disease conditions. Read more: Agarwal, Prashant, Daniel G. Greene, Scott Sherman, Kaitlyn Wendl, Leonela Vega, Hyunsoo Park, Roman Shimanovich, and Darren L. Reid. "Structural characterization and developability assessment of sustained release hydrogels for rapid implementation during preclinical studies." European Journal of Pharmaceutical Sciences (2020): 105689. https://www.sciencedirect.com/science/article/pii/S0928098720304772

“Highlights: Mesh size, modulus, injectability, viscosity, Tsol-gel are important structural parameters and developability constraints for hydrogels. Mesh size (SAXS/Rheology) of hydrogels > size (RH) of lysozyme suggesting that obstruction by polymer network doesn't hinder diffusion. ∼2x greater amount of lysozyme released from PLCL hydrogel as compared to PLGA, due to the higher viscosity of PLGA, increasing frictional drag on lysozyme and reducing its diffusivity. Tsol-gel (25 - 32°C) and injectability (injection force < 20N) confirmed that these hydrogels can be rapidly implemented during preclinical development. Abstract: 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.”