title: Hyaluronic acid (HA) presentation as a tool to modulate and control the receptor-mediated uptake of HA-coated nanoparticles.
abstract: The natural turnover of free hyaluronic acid (HA) is predominantly based on its CD44-mediated internalisation in leukocytes. In a phagocytic cell model (RAW 264.7 murine macrophages) we here provide conclusive evidence that this receptor-mediated mechanism endocytosis is responsible also of the uptake of materials where HA is used as a coating agent, in this case chitosan/triphosphate nanoparticles on whose surface HA is electrostatically adsorbed. Alginate-coated nanoparticles were used as a control and they appeared to undergo a qualitatively similar endocytic process, which was mediated by a different scavenging receptor yet to be identified. In this general picture, an important, modulating role appears to be played by how receptors can cluster around individual nanoparticles. The CD44 slow representation (24-48 h) enforces a limit in the amount of available HA internalisation receptors; therefore a higher affinity, and hence a higher degree of clustering, would yield a lower number of internalised nanoparticles. HA presentation can be varied by acting on nanoparticle structure/morphology, and our data suggest that a better presentation may be linked to both higher affinity and lower capacity/uptake rate. Paradoxically, this result would suggest that particles with a lower affinity for CD44 may allow a more efficient HA-mediated delivery of payloads.
authors.affiliation: School of Pharmacy, University of Manchester, Manchester, United Kingdom.
authors.forename: Abdulaziz
authors.initials: A
authors.lastname: Almalik
authors.forename: Shima
authors.initials: S
authors.lastname: Karimi
authors.forename: Sihem
authors.initials: S
authors.lastname: Ouasti
authors.forename: Roberto
authors.initials: R
authors.lastname: Donno
authors.forename: Christine
authors.initials: C
authors.lastname: Wandrey
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Day
authors.forename: Nicola
authors.initials: N
authors.lastname: Tirelli
mesh_terms: D000464:Alginates / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D003470:Culture Media; D004705:Endocytosis / Q000187:drug effects*; D020723:Glucuronic Acid / Q000494:pharmacology; D006603:Hexuronic Acids / Q000494:pharmacology; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000494:pharmacology*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011122:Polyphosphates / Q000494:pharmacology
chemical_list: D000464:Alginates; D020099:Coated Materials, Biocompatible; D003470:Culture Media; D006603:Hexuronic Acids; D018960:Hyaluronan Receptors; D011122:Polyphosphates; D020723:Glucuronic Acid; D006820:Hyaluronic Acid; D048271:Chitosan; C005692:triphosphoric acid