| Autor: |
Mantooth SM; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27606, United States., Hancock AM; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27606, United States., Thompson PM; Molecular Education, Technology and Research Innovation Center, North Carolina State University, Raleigh, North Carolina 27606, United States.; Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, North Carolina 27606, United States., Varghese P J G; Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina 27606, United States., Meritet DM; Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina 27606, United States., Vrabel MR; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27606, United States., Hu J; Department of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, North Carolina 27606, United States., Zaharoff DA; Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, North Carolina 27606, United States. |
| Abstrakt: |
Localized delivery of immunotherapeutics within a tumor has the potential to reduce systemic toxicities and improve treatment outcomes in cancer patients. Unfortunately, local retention of therapeutics following intratumoral injection is problematic and is insufficiently considered. Dense tumor architectures and high interstitial pressures rapidly exclude injections of saline and other low-viscosity solutions. Hydrogel-based delivery systems, on the other hand, can resist shear forces that cause tumor leakage and thus stand to improve the local retention of coformulated therapeutics. The goal of the present work was to construct a novel, injectable hydrogel that could be tuned for localized immunotherapy delivery. A chitosan-based hydrogel, called XCSgel, was developed and subsequently characterized. Nuclear magnetic resonance studies were performed to describe the chemical properties of the new entity, while cryo-scanning electron microscopy allowed for visualization of the hydrogel's cross-linked network. Rheology experiments demonstrated that XCSgel was shear-thinning and self-healing. Biocompatibility studies, both in vitro and in vivo, showed that XCSgel was nontoxic and induced transient mild-to-moderate inflammation. Release studies revealed that coformulated immunotherapeutics were released over days to weeks in a charge-dependent manner. Overall, XCSgel displayed several clinically important features, including injectability, biocompatibility, and imageability. Furthermore, the properties of XCSgel could also be controlled to tune the release of coformulated immunotherapeutics. |
