The passive diffusion of macromolecules through the human skin is limited by their large volume and ability to form hydrogen bonds. However, several vaccines penetrate the skin and evoke an immunological response and polysaccharides have been successfully and widely applied through the skin. The few data reported in literature emphasized that lipophilicity and molecular size, which rule the transdermal permeation of small molecules, cannot be taken as effective factors also for biomacromolecules. The present work provides a relationship between diffusion processes through the human epidermis of hyaluronans (HA) and their conformational properties. Low- and medium-molecular weight HA and the corresponding derivatives at two degrees of sulfation (HAS) were tested. The localization and the diffusion pathway of HA through human epidermis were followed using a FITC-labeled HA. The in vitro penetration experiments evidenced that HAs cross the epidermis mainly through a transcellular route. The higher the molecular weight, the higher the permeated amount. The epidermis resulted more permeable to the HAS than HA even if the permeated amount increases decreasing the degree of sulfation. The molecular dynamics study evidenced how the observed permeation behaviour can find compelling explanations in the conformational profiles. The permeation increases with the capacity to assume extended and flexible structures as encoded by the values of radius of gyration: the highest the values of radius of gyration, the highest the permeated amount. This trend can be explained considering that extended conformations can easily adapt themselves to the human stratum corneum environment.

The role of the conformational profile of polysaccharides on skin penetration: the case of hyaluronan and sulfates thereof / F. Cilurzo, F. Selmin, C.G.M. Gennari, G. Vistoli, F. Gardoni, S. Franzé, A. Casiraghi, P. Minghetti, L. Montanari - In: Atti del Congresso Adritelf[s.l] : Università degli Studi di Firenze, 2012 Sep. - pp. 74-74 (( Intervento presentato al 22. convegno Simposio ADRITELF tenutosi a Firenze nel 2012.

The role of the conformational profile of polysaccharides on skin penetration: the case of hyaluronan and sulfates thereof

F. Cilurzo
Primo
;
F. Selmin
Secondo
;
C.G.M. Gennari;G. Vistoli;F. Gardoni;S. Franzé;A. Casiraghi;P. Minghetti
Penultimo
;
L. Montanari
Ultimo
2012

Abstract

The passive diffusion of macromolecules through the human skin is limited by their large volume and ability to form hydrogen bonds. However, several vaccines penetrate the skin and evoke an immunological response and polysaccharides have been successfully and widely applied through the skin. The few data reported in literature emphasized that lipophilicity and molecular size, which rule the transdermal permeation of small molecules, cannot be taken as effective factors also for biomacromolecules. The present work provides a relationship between diffusion processes through the human epidermis of hyaluronans (HA) and their conformational properties. Low- and medium-molecular weight HA and the corresponding derivatives at two degrees of sulfation (HAS) were tested. The localization and the diffusion pathway of HA through human epidermis were followed using a FITC-labeled HA. The in vitro penetration experiments evidenced that HAs cross the epidermis mainly through a transcellular route. The higher the molecular weight, the higher the permeated amount. The epidermis resulted more permeable to the HAS than HA even if the permeated amount increases decreasing the degree of sulfation. The molecular dynamics study evidenced how the observed permeation behaviour can find compelling explanations in the conformational profiles. The permeation increases with the capacity to assume extended and flexible structures as encoded by the values of radius of gyration: the highest the values of radius of gyration, the highest the permeated amount. This trend can be explained considering that extended conformations can easily adapt themselves to the human stratum corneum environment.
Settore CHIM/09 - Farmaceutico Tecnologico Applicativo
Settore CHIM/08 - Chimica Farmaceutica
Settore BIO/14 - Farmacologia
set-2012
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/259156
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