posted on 2024-01-19, 13:34authored bySiena
M Mantooth, Asher M Hancock, Peter M Thompson, George Varghese P J, Danielle M Meritet, Maura R Vrabel, Jingjie Hu, David A Zaharoff
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.