A Drug-Eluting Injectable Nanogel for Localized Delivery of Anticancer Drugs to Solid Tumors Publisher



Godau B^{1, 2} ; Samimi S^{1, 2} ; Seyfoori A^{1, 2} ; Samiei E^{1, 2} ; Khani T³ ; Naserzadeh P⁴ ; Najafabadi AH⁵ ; Lesha E⁶ ; Majidzadeha K⁷ ; Ashtari B⁸ ; Charest G⁹ ; Morin C⁹ ; Fortin D⁹ ; Akbari M^{1, 2, 5}
Source: Pharmaceutics Published:2023

Abstract

Systemically administered chemotherapy reduces the efficiency of the anticancer agent at the target tumor tissue and results in distributed drug to non-target organs, inducing negative side effects commonly associated with chemotherapy and necessitating repeated administration. Injectable hydrogels present themselves as a potential platform for non-invasive local delivery vehicles that can serve as a slow-releasing drug depot that fills tumor vasculature, tissue, or resection cavities. Herein, we have systematically formulated and tested an injectable shear-thinning hydrogel (STH) with a highly manipulable release profile for delivering doxorubicin, a common chemotherapeutic. By detailed characterization of the STH physical properties and degradation and release dynamics, we selected top candidates for testing in cancer models of increasing biomimicry. Two-dimensional cell culture, tumor-on-a-chip, and small animal models were used to demonstrate the high anticancer potential and reduced systemic toxicity of the STH that exhibits long-term (up to 80 days) doxorubicin release profiles for treatment of breast cancer and glioblastoma. The drug-loaded STH injected into tumor tissue was shown to increase overall survival in breast tumor- and glioblastoma-bearing animal models by 50% for 22 days and 25% for 52 days, respectively, showing high potential for localized, less frequent treatment of oncologic disease with reduced dosage requirements. © 2023 by the authors.