Molecular Pharmaceutics (Tidskrift)

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Journal: Molecular Pharmaceutics
Manuscript ID : mp-2021-00235z
Title : "Rationalizing the design of HA-liposomes for targeting epidermal layers: a combination of molecular dynamic and experimental evidences"
Author(s): Franzè, Silvia; Rama, Francesco; Rocco, Paolo; Debernardi, Michela; Bincoletto, Valeria; Arpicco, Silvia; Cilurzo, Francesco

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Manuscript Abstract for mp-2021-00235z:

Hyaluronan (HA) is widely exploited as a targeting agent in the design of drug delivery systems intended for parenteral administration, while it is still poorly investigated for the treatment of skin pathologies. Nevertheless, HA has been used to improve the skin penetration of co-administered compounds and its main receptor, CD44, is overexpressed in different diseased skin tissues. With the aim of proposing HA-decorated deformable liposomes (HA-lip) to target the epidermis, this work provides new insights on the effect of different formulative variables (i.e. HA doses and distribution, lipid anchor and concentration) on skin penetration pattern of HA-lip. A combined approach based on experimental deformability assay and molecular dynamic simulations was used to rationalize the selection of the best lipid anchor among phosphoethanolamines with different physico-chemical properties. Hydration (H) and post-insertion (PI) methods allowed to obtain HA-lip decorated either on both membrane faces or on the outer one. It was found that HA exerts a dose-dependent stiffening effect on the bilayer that depends also on the spatial organization of the polysaccharide, being greater when HA is present also on the inner face of liposomes. In vitro skin permeation studies performed using human skin as membrane and resveratrol-loaded HA-lip highlighted, for the first time, the possibility to tune the drug delivery in the skin by controlling HA density on liposomal surface, favoring penetration or permeation of the carried drug depending on the target pathology.

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Period7 apr. 2021
Typ av tidskriftTidskrift