Nanocarrier-hydrogel composite delivery systems for precision drug release.

Hydrogels are a class of biomaterials widely implemented in medical applications due to their biocompatibility and biodegradability. Despite the many successes of hydrogel-based delivery systems, there remain challenges to hydrogel drug delivery such as a burst release at the time of administration, a limited ability to encapsulate certain types of drugs (i.e., hydrophobic drugs, proteins, antibodies, and nucleic acids), and poor tunability of geometry and shape for controlled drug release. This review discusses two main important advances in hydrogel fabrication for precision drug release: first, the incorporation of nanocarriers to diversify their drug loading capability, and second, the design of hydrogels using 3D printing to precisely control drug dosing and release kinetics via high-resolution structures and geometries. We also outline ongoing challenges and discuss opportunities to further optimize drug release from hydrogels for personalized medicine. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.

Use of FLOSEAL® as a scaffold and its impact on induced neural stem cell phenotype, persistence, and efficacy.

Induced neural stem cells (iNSCs) have emerged as a promising therapeutic platform for glioblastoma (GBM). iNSCs have the innate ability to home to tumor foci, making them ideal carriers for antitumor payloads. However, the in vivo persistence of iNSCs limits their therapeutic potential. We hypothesized that by encapsulating iNSCs in the FDA-approved, hemostatic matrix FLOSEAL®, we could increase their persistence and, as a result, therapeutic durability. Encapsulated iNSCs persisted for 95 days, whereas iNSCs injected into the brain parenchyma persisted only 2 weeks in mice. Two orthotopic GBM tumor models were used to test the efficacy of encapsulated iNSCs. In the GBM8 tumor model, mice that received therapeutic iNSCs encapsulated in FLOSEAL® survived 30 to 60 days longer than mice that received nonencapsulated cells. However, the U87 tumor model showed no significant differences in survival between these two groups, likely due to the more solid and dense nature of the tumor. Interestingly, the interaction of iNSCs with FLOSEAL® appears to downregulate some markers of proliferation, anti-apoptosis, migration, and therapy which could also play a role in treatment efficacy and durability. Our results demonstrate that while FLOSEAL® significantly improves iNSC persistence, this alone is insufficient to enhance therapeutic durability.