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Nanoparticules recouvertes de dérivés amphiphiles de hyaluronate pour la vectorisation de molécules d'intérêt pour le traitement des pathologies de l'articulation

Abstract : A defect in articular cartilage yield to a biological response of the chondrocytes but it is not sufficient to stop the damage or heal the tissue. The non-chirurgical therapies available are based on anti-inflammatory, to relieve the pain. But, many molecules which might have therapeutic effects are not used because of poor bioavailability or severe side effects. Here, we described the elaboration of polymeric nanoparticles that can enhance articular bioavailability of entrapped drugs. One can reach this goal by using HA derivatives at the surface of such particles. HA is a polysaccharide naturally present in the joint, with a strong affinity for one receptor expressed by the chondrocytes: CD44. Such an active targeting will allow the accumulation of drugs near or in the cells (internalization) and therefore, lead to biological effects with lower concentration. We chemically modified the HA by esterification with hydrophobic chains to confer tensio-actives properties. Then, those derivatives were used to stabilize the formulation of polymeric particles and the characterization (size, distribution and amount of HA derivatives present) was determined. The encapsulation of fluorescent probes proved in vitro an internalization by the chondrocytes. Moreover, intra-articular (ia) injection of particles in healthy rats did not generate any inflammation. Entrapment of molecules (HA or Chondroitin Sulfate) was possible but the size was higher and the encapsulated amount could not be precisely measured. This work is promising for new therapies in articular diseases, the ia injection of polymeric particles covered by HA derivatives allow an active targeting of the entrapped drugs
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https://hal.univ-lorraine.fr/tel-01749660
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Hervé Zille. Nanoparticules recouvertes de dérivés amphiphiles de hyaluronate pour la vectorisation de molécules d'intérêt pour le traitement des pathologies de l'articulation. Médecine humaine et pathologie. Université de Lorraine, 2012. Français. ⟨NNT : 2012LORR0320⟩. ⟨tel-01749660⟩

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