A novel biocompatible hyaluronic acid–chitosan hybrid hydrogel for osteoarthrosis therapy

[Display omitted] 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...

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Bibliographic Details
Published in:International journal of pharmaceutics 2015-04, Vol.483 (1-2), p.158-168
Main Authors: Kaderli, S., Boulocher, C., Pillet, E., Watrelot-Virieux, D., Rougemont, A.L., Roger, T., Viguier, E., Gurny, R., Scapozza, L., Jordan, O.
Format: Article
Language:English
Subjects:
Aged
Animals
Biocompatibility
Biocompatible Materials - administration & dosage
Biocompatible Materials - chemistry
Biocompatible Materials - pharmacology
Biopolymers
Cell Survival - drug effects
Chemical Sciences
Chitosan
Chitosan - administration & dosage
Chitosan - chemistry
Dose-Response Relationship, Drug
Fibroblasts - drug effects
Humans
Hyaluronic acid
Hyaluronic Acid - administration & dosage
Hyaluronic Acid - chemistry
Hybrid hydrogel
Hydrogels - administration & dosage
Hydrogels - chemistry
Hydrogels - pharmacology
Injections, Intra-Articular
Injections, Subcutaneous
Life Sciences
Male
Molecular Weight
Osteoarthritis - drug therapy
Osteoarthritis - pathology
Rabbits
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Viscosity
Viscosupplementation
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Summary:[Display omitted] 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2015.01.052