Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment

Abstract

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher ‘effective’ doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

pH Sensitive Pluronic Acid/Agarose-Hydrogels as Controlled Drug Delivery Carriers: Design, Characterization and Toxicity Evaluation

“…Thermograms of samples were documented using a DSC (8500, Perkin Elmer, American Fork, UT, USA). Nitrogenous atmosphere (20 mL/min) was used to carry out the measurements at heating rate of 10 • C/min and temperature range of about 30-600 • C [53].…”

Drug Delivery Systems for Localized Cancer Combination Therapy

“…These classifications include the bases of polymer composition (e.g., monopolymer, copolymer), physical structure (e.g., amorphous, crystalline, mixed), cross-linking (e.g., chemical, physical), physiological response (e.g., thermoresponsive, pH responsive, stimuli-responsive), and overall ionic charge (e.g., cation, anion, nonionic). These properties and hydrogel behavior can be tuned or modified throughout formulation to generate hydrogels with unique degradation rates and drug-releasing kinetics . Due to their high stability and water content, many different classes of drugs can be incorporated within these polymeric systems such as anticancer immunotherapies (e.g., antibodies, cell-based therapies) as well as other bioactive agents.…”

“…These properties and hydrogel behavior can be tuned or modified throughout formulation to generate hydrogels with unique degradation rates and drugreleasing kinetics. 91 Due to their high stability and water content, many different classes of drugs can be incorporated within these polymeric systems such as anticancer immunotherapies (e.g., antibodies, cell-based therapies) as well as other bioactive agents. It is critical to determine the physicochemical properties of the localized drug delivery system that will be suitable for effective loading and delivery of cargo, which is in part governed by the synthesis methods.…”

Unveiling the therapeutic potential of cabozantinib-loaded poly D,L-lactic-co-glycolic acid and polysarcosine nanoparticles in inducing apoptosis and cytotoxicity in human HepG2 hepatocellular carcinoma cell lines and in vivo anti-tumor activity in SCID female mice

“…From recent studies, it was confirmed that Cabozantinib specifically targets endothelial growth factor receptor types 1 (VEGFR-1) ( 6 ), endothelial growth factor receptor types 2 (VEGFR-2) ( 7 ), FMS-like tyrosine kinase 3 (FLT-3) ( 8 ); which ultimately results in the demotion of angiogenesis and proliferation of malignant tumour ( 9 , 10 ). As far as liver cancer is concerned ( 11 ), it is the sixth most frequently recognized cancer and the fourth leading cause of cancer mortality across the globe ( 12 , 13 ). As per the WHO report, nearly 782,000 deaths have been recorded due to liver cancer, and surprisingly, liver cancer is more common in men than in women.…”