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



Godau B1, 2 ; Samimi S1, 2 ; Seyfoori A1, 2 ; Samiei E1, 2 ; Khani T3 ; Naserzadeh P4 ; Najafabadi AH5 ; Lesha E6 ; Majidzadeha K7 ; Ashtari B8 ; Charest G9 ; Morin C9 ; Fortin D9 ; Akbari M1, 2, 5
Authors
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Authors Affiliations
  1. 1. Laboratory for Innovations in MicroEngineering (LiME), Department of Mechanical Engineering, University of Victoria, Victoria, V8P 5C2, BC, Canada
  2. 2. Center for Advanced Materials and Related Technology (CAMTEC), University of Victoria, Victoria, V8P 5C2, BC, Canada
  3. 3. Preclinical Lab, Core Facility, Tehran University of Medical Sciences, Tehran, 1417755354, Iran
  4. 4. Endocrine Research Center, Institute of Endocrinology and Metabolism, Iran University of Medical Sciences, Tehran, 88945173, Iran
  5. 5. Terasaki Institute for Biomedical Innovations, Los Angeles, 90050, CA, United States
  6. 6. Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, 38163, TN, United States
  7. 7. Genetics Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, No. 146, South Gandhi Ave., Vanak Sq., P.O. BOX 1517964311, Tehran, 1684613114, Iran
  8. 8. Department of Medical Nanotechnology, Faculty of Advance Technologies in Medicine, Iran University of Medical Sciences, Tehran, 1449614535, Iran
  9. 9. Department of Surgery, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, J1K 2R1, QC, Canada

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.
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