Synthesis and characterization of thiolated carboxymethyl chitosan-graft-cyclodextrin nanoparticles as a drug delivery vehicle for albendazole

Abstract

A new strategy for the synthesis of thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles by an ionic-gelation method is presented. The synthetic approach was based on the utilization of 1,6-hexamethylene diisocyanate during cyclodextrin grafting onto carboxymethyl chitosan. The use of the 1,6-hexamethylene diisocyanate resulted in reactions between cyclodextrin and active sites at the C6-position of chitosan, and preserved amino groups of chitosan for subsequent reactions with thioglycolic acid, as the thiolating agent, and tripolyphosphate, as the gelling counterion. Various methods such as scanning electron microscopy, rheology and in vitro release studies were employed to exhibit significant features of the nanoparticles for mucosal albendazole delivery applications. It was found that the thiolated carboxymethyl chitosan-g-cyclodextrin nanoparticles prepared using an aqueous solution containing 1 wt% of tripolyphosphate and having 115.65 (μmol/g polymer) of grafted thiol groups show both the highest mucoadhesive properties and the highest albendazole entrapment efficiency. The latter was confirmed theoretically by calculating the enthalpy of mixing of albendazole in the above thiolated chitosan polymer.

Exploring the Preparation of Albendazole-Loaded Chitosan-Tripolyphosphate Nanoparticles

“…Cyclodextrins (CDs) are cup-shaped molecules with hydrophobic cavities and hydrophilic exteriors that can interact with various hydrophobic guest molecules to form supramolecular inclusion complexes [6,7]. CDs have been exploited to enhance the bioavailability of insoluble drugs by increasing drug solubility and permeability.…”

“…CDs have been exploited to enhance the bioavailability of insoluble drugs by increasing drug solubility and permeability. Moreover, the safety of CDs in humans has been well established [6,8]. …”

Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

“…Different strategies have been investigated to solve the limited aqueous solubility of benzimidazoles, including the use of surfactants, such as polysorbates and bile salts, or co-solvents (Daniel-Mwambete et al, 2004;Miranda et al, 2011;Pradines et al, 2014). There is evidence that complexation with cyclodextrins (CDs) can increase the oral bioavailability of benzimidazoles (Evrard et al, 2002;Moriwaki et al, 2008;Pourgholami, Wangoo, Morris, 2008;Palomares-Alonso et al, 2010;Kumar et al, 2011a;Kumar et al, 2011b;Alamdarnejad et al, 2013;De Jaeghere et al, 2013;Pradines et al, 2014;Ferreira et al, 2015). CDs are known for increasing the solubility, dissolution efficiency, and bioavailability of different drugs through the formation of inclusion complexes.…”

Classification of stimuli–responsive polymers as anticancer drug delivery systems

“…Polymeric carriers are one of the most commonly used approaches (Alamdarnejad et al, 2013;Taranejoo et al 2014). Soluble polymeric drug carriers can improve drug pharmacokinetics and reduce systemic toxicity by delivering the drug to the tumor tissue, thanks to the higher permeability of tumor vasculature, known as the enhanced permeability and retention (EPR) effect (Matsumura & Maeda, 1986).…”