Hydrogels have received significant attention for controlled drug-delivery applications on account of their similarity to soft biological tissues and highly tunable properties. This invention achieves localized drug delivery of multiple components in a minimally invasive manner, with applications in controlled release technologies that, among other uses, may treat macular degeneration, diabetes, and may provide sustainable corticosteriod delivery.
Shear-thinning hydrogels are water-swollen, dynamically crosslinked polymer networks that exhibit viscous flow under shear stress (shear-thinning) and rapid recovery when the applied stress is relaxed (self-healing). These properties afford minimally invasive implantation in vivo through direct injection or catheter delivery to tissues, contributing to a rapid gain in interest in their application for drug delivery and tissue engineering.
To date, the best candidate shear-thinning hydrogels are limited by at least one of the following constraints: non-biocompatible precursor components; expensive, difficult and time-intensive synthesis; difficulty injecting through a needle or catheter; or slow self-healing behavior. The Inventors have developed a system formed from FDA-approved and commonly used biocompatible precursor components. The gel is formed in a low-cost, facile and short synthesis that is fully scalable to increased production. The shear-thinning hydrogels can be injected through high gauge needles and self-heal in a matter of seconds, making them fully compatible with in vivo applications.
Overall, this technology presents a versatile injectable hydrogel that can be employed as a viscosity modifier in a range of applications, and for the controlled delivery of therapeutics with minimally invasive application in vivo. The gel is formed from a two-component system of PLA-b-PEG NPs and modified HPMC. Owing to the non-covalent interactions between the PLA-b-PEG NPs and HPMC, the hydrogels flow under applied strain and recover in a matter of seconds when the strain is relaxed, even after multiple shear-thinning cycles. In this manner, the material can be injected into a desired location inside or outside of the body, conform to the local geometry, and rapidly reform a stable hydrogel. Thus, the system is amenable to minimally invasive placement within the body through syringe needle or catheter-based injection.
Additionally, the inclusion of PLA-b-PEG NPs facilitates a high-loading content of hydrophobic molecules within the gel, while a second, hydrophilic molecule can be loaded simultaneously into the aqueous phase of the gel. Owing to the nature of the nanostructure of the self-assembled gel, the NPs remain suspended evenly throughout the bulk of the hydrogel such that the release of molecules is governed both by material erosion and diffusion. In this manner, multiple therapeutics can be delivered with a complex multi-stage release profile.
Gel formed from low-cost and biocompatible components
Low-cost, short and facile process of synthesis
Injectable gels self-heal in seconds, affording minimally invasive implantation
Process allows multi-stage release of multiple therapeutics for localized drug delivery