Matrix Metalloproteinase- and pH-Sensitive Nanoparticle System Enhances Drug Retention and Penetration in Glioblastoma.

Glioblastoma (GBM) is a primary malignant brain tumor with limited therapeutic options. One promising approach is local drug delivery, but the efficacy is hindered by limited diffusion and retention. To address this, we synthesized and developed a dual-sensitive nanoparticle (Dual-NP) system, formed between a dendrimer and dextran NPs, bound by a dual-sensitive [matrix metalloproteinase (MMP) and pH] linker designed to disassemble rapidly in the tumor microenvironment. The disassembly prompts the in situ formation of nanogels via a Schiff base reaction, prolonging Dual-NP retention and releasing small doxorubicin (Dox)-conjugated dendrimer NPs over time. The Dual-NPs were able to penetrate deep into 3D spheroid models and detected at the tumor site up to 6 days after a single intratumoral injection in an orthotopic mouse model of GBM. The prolonged presence of Dual-NPs in the tumor tissue resulted in a significant delay in tumor growth and an overall increase in survival compared to untreated or Dox-conjugated dendrimer NPs alone. This Dual-NP system has the potential to deliver a range of therapeutics for efficiently treating GBM and other solid tumors.

Sprayable Hydrogel Sealant for Gastrointestinal Wound Shielding.

Naturally occurring internal bleeding, such as in stomach ulcers, and complications following interventions, such as polyp resection post-colonoscopy, may result in delayed (5-7 days) post-operative adverse events-such as bleeding, intestinal wall perforation, and leakage. Current solutions for controlling intra- and post-procedural complications are limited in effectiveness. Hemostatic powders only provide a temporary solution due to their short-term adhesion to GI mucosal tissues (less than 48 h). In this study, a sprayable adhesive hydrogel for facile application and sustained adhesion to GI lesions is developed using clinically available endoscopes. Upon spraying, the biomaterial (based on polyethyleneimine-modified Pluronic micelles precursor and oxidized dextran) instantly gels upon contact with the tissue, forming an adhesive shield. In vitro and in vivo studies in guinea pigs, rabbits, and pig models confirm the safety and efficacy of this biomaterial in colonic and acidic stomach lesions. The authors' findings highlight that this family of hydrogels ensures prolonged tissue protection (3-7 days), facilitates wound healing, and minimizes the risk of delayed complications. Overall, this technology offers a readily adoptable approach for gastrointestinal wound management.

Sprayable Hydrogel for Instant Sealing of Vascular Anastomosis.

Bleeding-related complications following vascular surgeries occur in up to half of the patients-500 000 cases annually in the United States alone. This results in additional procedures, increased mortality rate, and prolonged hospitalization, posing a burden on the healthcare system. Commercially available materials rely, in large, on forming covalent bonds between the tissue and the biomaterial to achieve adhesion. Here, it is shown that a biomaterial based on oxidized alginate and oxidized dextran together with polyamidoamine (PAMAM) dendrimer amine provides simultaneous electrostatic and covalent interactions between the biomaterial and the tissue, maximizing adhesion. This study finds that the material withstands supraphysiological pressures (≈300 mmHg) and prevents bleeding in a rabbit aortic puncture model and in a pig carotid bilateral poly(tetrafluoroethylene) graft model-achieving superior performance to commercially available materials such as Tisseel and BioGlue. Material biocompatibility is validated in comprehensive in vitro and in vivo studies in accordance with the US Food and Drug Administration (FDA) guidelines, including in vitro neutral red uptake test, subcutaneous implantation in rabbits, ames genotoxicity, and guinea pig maximization test. This material has the potential to provide with adequate seal and reduced complications following complex vascular surgeries, including hard-to-seal tissue-graft interfaces.