Efficacy, Pharmacokinetics, and Biodistribution of Thermosensitive Chitosan/β-Glycerophosphate Hydrogel Loaded with Docetaxel

Abstract

Abstract. Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.

Ionically Crosslinked Thermoresponsive Chitosan Hydrogels formed In Situ: A Conceptual Basis for Deeper Understanding

“…Modifications of chitosan chemistry or solutions can improve the interaction with bioactive elements and improve cell attachment . The addition of β‐glycerolphosphate (β‐GP) increased the pH of chitosan solutions to a neutral value without phase separation . The formation of 3D structures plays an important role in the utility of chitosan‐based systems.…”

Recent Advances in Chitosan-Based Nanomedicines for Cancer Chemotherapy

“…Li et al developed a thermosensitive chitosan/β-glycerophosphate (C/GP) hydrogel loaded with docetaxel DTX for intratumoral delivery [108]. In vivo study of DTX-loaded C/GP hydrogel (DTX-C/GP) at 20 mg/kg in H22 tumorbearing mice demonstrated significant reduction in tumor volume.…”

Vancomycin-loaded HPMC microparticles embedded within injectable thermosensitive chitosan hydrogels

“…Thermosensitive hydrogels made of various polymers and biopolymers have been widely investigated as a system of local drug delivery. Among them, chitosan/glycerophosphate (Ch/Gp) hydrogel has emerged as a unique kind of injectable thermosensitive hydrogel owing to its excellent properties, including ready availability, biocompatibility, biodegradability, as well as non-toxicity (Ghasemi-Tahrir et al 2015 ; Li et al 2014 ). Therefore, thermosensitive Ch/Gp hydrogel is a good candidate for implantation of antibiotic loaded polymeric systems directly to the site of infection.…”