Novel Injectable Neutral Solutions of Chitosan form Biodegradable Gels in situ

Faculty of Pharmacy, Université de Montréal, Montréal, Quebec, Canada
Biomaterials (Impact Factor: 8.56). 12/2000; 21(21):2155-61. DOI: 10.1016/S0142-9612(00)00116-2
Source: PubMed


A novel approach to provide, thermally sensitive neutral solutions based on chitosan/polyol salt combinations is described. These formulations possess a physiological pH and can be held liquid below room temperature for encapsulating living cells and therapeutic proteins; they form monolithic gels at body temperature. When injected in vivo the liquid formulations turn into gel implants in situ. This system was used successfully to deliver biologically active growth factors in vivo as well as an encapsulating matrix for living chondrocytes for tissue engineering applications. This study reports for the first time the use of polymer/polyol salt aqueous solutions as gelling systems, suggesting the discovery of a prototype for a new family of thermosetting gels highly compatible with biological compounds.

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Available from: Caroline Hoemann, Oct 02, 2014
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    • "A novel injectable in situ gelling thermosensitive chitosan/glycerophosphate formulation has been proposed in recent years (Chenite et al., 2000Chenite et al., , 2001Ruel-Gariépy, Hildgen, Gupta, & Leroux, 2002). First, chitosan and -glycerophosphate solutions are prepared in deionized water. "
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    ABSTRACT: Chitosan is non-toxic, biocompatible and biodegradable polysaccharide composed of glucosamine and derived by deacetylation of chitin. Chitosan thermosensitive hydrogel has been developed to form a gel in situ, precluding the need for surgical implantation. In this review, the recent advances in chitosan thermosensitive hydrogels based on different glycerophosphate are summarized. The hydrogel is prepared with chitosan and β-glycerophosphate or αβ-glycerophosphate which is liquid at room temperature and transits into gel as temperature increases. The gelation mechanism may involve multiple interactions between chitosan, glycerophosphate, and water. The solution behavior, rheological and physicochemical properties, and gelation process of the hydrogel are affected not only by the molecule weight, deacetylation degree, and concentration of chitosan, but also by the kind and concentration of glycerophosphate. The properties and the three-dimensional networks of the hydrogel offer them wide applications in biomedical field including local drug delivery and tissue engineering. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Full-text · Article · Mar 2015 · Carbohydrate Polymers
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    • "Indeed, this pro-inflammatory activity is dependent on the source, purity and chemical modification of Cs but has been found to be resolved in the body without leading to a foreign body reaction (Barbosa et al., 2010; Chenite et al., 2000; Patois et al., 2009; Peluso et al., 1994; Usami et al., 1994a,b; VandeVord et al., 2002). Overall, chitosan is considered to be safe, and its LD 50 is 10 g/kg for subcutaneous injection in mice, although severe pneumonia was found in dogs (Kumar et al., 2004; Minami et al., 1996; Usami et al., 1998). "
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    ABSTRACT: A conventional therapy for the treatment of osteoarthrosis is intra-articular injection of hyaluronic acid, which requires repeated, frequent injections. To extend the viscosupplementation effect of hyaluronic acid, we propose to associate it with another biopolymer in the form of a hybrid hydrogel. Chitosan was chosen because of its structural similarity to synovial glycosaminoglycans, its anti-inflammatory effects and its ability to promote cartilage growth. To avoid polyelectrolyte aggregation and obtain transparent, homogeneous gels, chitosan was reacetylated to a 50% degree, and different salts and formulation buffers were investigated. The biocompatibility of the hybrid gels was tested in vitro on human arthrosic synoviocytes, and in vivo assessments were made 1 week after subcutaneous injection in rats and 1 month after intra-articular injection in rabbits. Hyaluronic acid–chitosan polyelectrolyte complexes were prevented by cationic complexation of the negative charges of hyaluronic acid. The different salts tested were found to alter the viscosity and thermal degradation of the gels. Good biocompatibility was observed in rats, although the calcium-containing formulation induced calcium deposits after 1 week. The sodium chloride formulation was further tested in rabbits and did not show acute clinical signs of pain or inflammation. Hybrid HA–Cs hydrogels may be a valuable alternative viscosupplementation agent.
    Full-text · Article · Feb 2015 · International Journal of Pharmaceutics
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    • "Among all of these forms, the hydrogel, especially the thermosensitive hydrogel has attracted much attention because it can be applied as an injectable material for irregular-shaped tissue repair. Chitosan, combined with ␤-glycerophosphate disodium (␤-GP), is an outstanding in situ gel-forming system, which was first reported by Chenite et al. (2000). This system is available at a physiologically acceptable pH and is liquid at room temperature. "
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    ABSTRACT: In order to get a water-soluble in situ gel-forming system, a thiolated chitosan, chitosan-4-thio-butylamidine (CS-TBA) conjugate was synthesized and used to replace the unmodified chitosan in the application of the in situ gel-forming system. A novel thermo-sensitive hydrogel was prepared based on CS-TBA/hydroxyapatite (HA)/beta-glycerophosphate disodium (β-GP). The gel formation, rheological properties, morphology, degradation, cytotoxicity, as well as protein release process of the novel gel system were investigated in this study. The CS-TBA/HA/β-GP gel showed a higher storage modulus (G') and loss modulus (G″) and a decreased bovine serum albumin (BSA) release rate which was maintained the protein release for a longer time compared with the unmodified chitosan (CS)/HA/β-GP gel, due to the existence of thiol groups and/or disulfide bonds. The CS-TBA/HA/β-GP gel has a porous structure with a uniform distribution of nano-hydroxyapatite, an appropriate degradation rate and low cytotoxicity, showing potential applications in drug delivery and tissue engineering.
    Full-text · Article · Sep 2014 · Carbohydrate Polymers
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