Chitosan-Based Thermosensitive Hydrogel Containing Liposomes for Sustained Delivery of Cytarabine

Abstract

Sustained release thermosensitive solution containing cytarabineloaded liposome delivery system offers the possibility of reduced dosing frequency and sustained drug action. Biodegradable and biocompatible chitosan-beta-glycerophosphate (C-GP) thermosensitive solution having the property to gel at body temperature and to maintain its physical integrity for longer period of time was used. The C-GP solution containing cytarabine-loaded liposomes (CGPCLL) was studied, and the results showed that the cytarabine liposomes were capable of high encapsulation efficiency (85.2 ± 2.58%) with the mean diameter of 220 ± 6.9 nm of extruded cytarabine-loaded liposome. Furthermore, transmission electron microscopy showed spherical-shaped liposomes after extrusion with smooth surface. In vitro studies of CGPCLL in PBS buffer showed that this system can sustain release of encapsulated drug for more than 60 h compared with drug-loaded liposomal suspension (upto 48 h). Pharmacokinetic studies of CGPCLL resulted in higher t 1/2 (28.86 h) and AUC 2526.88 μg/mL h compared with cytarabine-loaded liposomal suspension (CLLS) and C-GP containing free cytarabine (CGPFC) in rats. CGPCLL was capable of sustaining the cytarabine release for more than 60 h in vivo compared with CLLS and CGPFC which showed maximum amount of drug release within 42 and 10 h, respectively. Thus, these results showed that the CGPCLL gels at body temperature and can sustain the delivery of cytarabine effectively.

Cyclodextrin-polyhydrazine degradable gels for hydrophobic drug delivery

“…Drug solubilisation using colloidal carriers, such as liposomes and surfactant micellar structures has been a common solution. Typically, drug-loaded micelles or liposomes are dispersed into aqueous solutions of crosslinked networks during the synthesis processes [4,5]. The limitations of this solubilisation strategy often include poor shelf-life and stability which may change optical and mechanical properties of the hydrogel, difficulty in targeting specific tissues and rapid clearance by phagocytic cells of the reticuloendothelial system [6][7][8].…”

Enhanced antitumor efficacy of gemcitabine-loaded temperature-sensitive liposome by hyperthermia in tumor-bearing mice

“…It is well known that liposomes made of naturally occurring lipids are biocompatible carriers and their application as a drug delivery system reduces the drug toxicity and increases the therapeutic efficacy. Temperature-sensitive liposome (TSL) is a liposomal formulation with an excellent temperature-dependent release property [2][3][4][5][6][7] . TSL has been developed and used in combination with hyperthermia (HT) to increase the release of encapsulated anticancer drugs at or around tumor sites and to decrease the severity of the side effects associated with the drug molecule 8,9 .…”

Development of cytarabine prodrugs and delivery systems for leukemia treatment

“…The cytarabine encapsulated liposome has been studied with thermosensitive hydrogels [76]. The hydrogel was based on the biodegradable chitosan and βglycerophosphate (C-GP) that are thermosensitive and act as a thermal trigger to regulate the drug release from encapsulation.…”