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

ABSTRACT 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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    • "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.
    International Journal of Pharmaceutics 02/2015; 483(1-2). DOI:10.1016/j.ijpharm.2015.01.052 · 3.65 Impact Factor
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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.
    Carbohydrate Polymers 09/2014; 110C:62-69. DOI:10.1016/j.carbpol.2014.03.065 · 4.07 Impact Factor
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    • "It has been reported by several researchers that CS/b-Gp retains biologic activity of the incorporated therapeutics and growth factors (Chenite et al., 2000). CS/Gp formulation loaded with paclitaxel indicated higher tumor inhibition capability compared to free Taxol Õ after being injected intratumorally (Ruel-Gariépy et. "
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    ABSTRACT: Abstract Injectable In situ gel-forming chitosan/β-glycerol phosphate (CS/β-Gp) solution can be introduced into the body in a minimally invasive manner prior to solidifying within the target tissue. This hydrogel is a good candidate for achieving a prolonged drug delivery system for insulin considering its high molecular weight. In addition to the physicochemical characterization of this hydrogel, in vitro and in vivo applications were studied as a sustained insulin delivery system. In the in vitro release studies, 19-63% of total insulin was released from the CS/β-Gp hydrogel within 150 h at different β-Gp and insulin concentrations. The best formulation was selected for in vivo experimentation to control the plasma glucose of diabetic mice models. The hypoglycemic effect of this formulation following subcutaneous injection in diabetic mice lasted 5 d, significantly longer than that of free insulin solution which lasted several hours.
    Drug Delivery 07/2014; DOI:10.3109/10717544.2014.932861 · 2.56 Impact Factor
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