Journal Name: Molecular Pharmaceutics
Manuscript ID : mp-2021-00235z.R2
Title : "Rationalizing the design of hyaluronic acid liposomes for targeting epidermal layers: a combination of molecular dynamic and experimental evidence"
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.R2:
This work provides information on the features of low molecular weight hyaluronic acid (HA)-decorated liposomes to target resveratrol (RSV) in the skin. Deformable liposomes were made of soy-phosphatidylcholine with Tween 80 as the fluidizing agent. For HA conjugation, three different phosphoethanolamines were tested: 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The different phosphoethanolamine-HA conjugates were inserted into the liposome bilayer by hydration (HA on both faces of the bilayer) or by the postinsertion method (HA only on the external face of the bilayer). The effect of these variables on deformability was experimentally assessed by an in-house method (K value, the lower the value, the higher the deformability) and molecular dynamics (MD) simulations. The results showed that the K values of HA-liposomes obtained by hydration were higher than the K values of HA-liposomes prepared by postinsertion, and both were at least 10-fold higher than the K values of the corresponding plain liposomes. The nature of the lipid anchor played a key role in deformability (DMPE>DOPE>DPPE) with high variability in the case of DOPE formulations. These data were justified by the trends found in silico for the bilayer bending modulus and the HA end-to-end distance. In addition to liposome flexibility, the HA extent seems to be the key factor governing the skin penetration of RSV. The higher the extent is, the larger the amount of the drug retained in the skin. Regarding skin permeation, a parabolic trend was recorded, and the optimal amount to favour skin permeation was an approximately 30 HA/phospholipid (µg/mmol) ratio. This study reports the first evidence that it is possible to control drug delivery in the skin by tuning the amount of HA on the vesicle surface.
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|Period||27 juli 2021|
|Typ av tidskrift||Tidskrift|