In-Silico Modelling of Transdermal Delivery of Macromolecule Drugs Assisted by a Skin Stretching Hypobaric Device.
Pharm Res
; 40(1): 295-305, 2023 Jan.
Article
em En
| MEDLINE
| ID: mdl-36348132
ABSTRACT
OBJECTIVES:
To develop a simulation model to explore the interplay between mechanical stretch and diffusion of large molecules into the skin under locally applied hypobaric pressure, a novel penetration enhancement method.METHODS:
Finite element method was used to model the skin mechanical deformation and molecular diffusion processes, with validation against in-vitro transdermal permeation experiments. Simulations and experimental data were used together to investigate the transdermal permeation of large molecules under local hypobaric pressure.RESULTS:
Mechanical simulations resulted in skin stretching and thinning (20%-26% hair follicle diameter increase, and 21%-27% skin thickness reduction). Concentration of dextrans in the stratum corneum was below detection limit with and without hypobaric pressure. Concentrations in viable epidermis and dermis were not affected by hypobaric pressure (approximately 2 µg [Formula see text] cm-2). Permeation into the receptor fluid was substantially enhanced from below the detection limit at atmospheric pressure to up to 6 µg [Formula see text] cm-2 under hypobaric pressure. The in-silico simulations compared satisfactorily with the experimental results at atmospheric conditions. Under hypobaric pressure, satisfactory comparison was attained when the diffusion coefficients of dextrans in the skin layers were increased from [Formula see text] 10 µm2 [Formula see text] s-1 to between 200-500 µm2 [Formula see text] s-1.CONCLUSIONS:
Application of hypobaric pressure induces skin mechanical stretching and enlarges the hair follicle. This enlargement alone cannot satisfactorily explain the increased transdermal permeation into the receptor fluid under hypobaric pressure. The results from the in-silico simulations suggest that the application of hypobaric pressure increases diffusion in the skin, which leads to improved overall transdermal permeation.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pele
/
Dextranos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article