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Ultraflexible lipid vesicles allow topical absorption of cyclosporin A

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Abstract

Psoriasis and atopic dermatitis are widespread pathologies with a need to improve their treatment. Topical administration of cyclosporine A (CyA) could be used if targeted to the skin, thus avoiding systemic levels. Unfortunately, CyA molecular weight and lipophilicity prevent its diffusion through human skin. Four novel lipid vesicles have been prepared by different methodologies to overcome this problem. The vesicles were characterized in terms of particle size, size polydispersity, Z-potential, morphology, drug encapsulation, phospholipid content, and vesicle flexibility. Freeze-drying in presence and absence of cryoprotective agents was also performed, to guarantee long-term stability. The ability to deliver CyA into the skin was assessed using human epidermis in Franz diffusion cells and compared with the delivery of drug solutions with enhancers. The technical characteristics of four types of vesicle make them suitable to carry drugs. Moreover, these liposomal formulations were able to effectively deliver CyA in vitro into the skin. The present work introduces a promising approach for the topical treatment of skin pathologies with an immune component.

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Abbreviations

CyA:

Cyclosporine A

CL:

Conventional liposomes

CL-SON:

Sonicated conventional liposomes

CL-EXT:

Extruded conventional liposomes

Cv:

Concentration of drug in the donor compartment

DLS:

Dynamic light scattering

EE%:

Encapsulation efficiency

Etho:

Ethosomes

Etho-EXT:

Extruded ethosomes

HHSE:

Human heat-separated epidermis

J :

Flux

J max :

Maximum flux

J SS :

Steady-state flux

MLV:

Multilamellar vesicles

PBS:

Phosphate buffer solution

PC:

Phosphatidylcholine

PC%:

Phosphatidylcholine content

PDI:

Polydispersity index

Q :

Amount

S v :

Solubility of the drug in the vehicle

TEM:

Transmission electron microscopy

T1:

Transfersomes type 1

T1-SON:

Sonicated transfersomes type 1

T1-EXT:

Extruded transfersomes type 1

T2:

Transfersomes type 2

T2-SON:

Sonicated transfersomes type 2

T2-EXT:

Extruded transfersomes type 2

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Acknowledgments

The authors would like to thank Dra. Isabel Moreno, the surgery team and skin donors.

Funding

The authors would like to thank the Spanish Ministry of Economy and Competitiveness-FEDER (SAF2017-85806-R) and the Conselleria d’Educacio, Cultura i Esport of the Generalitat Valenciana “Proyecto Emergente GV2015-054”, which supported this work.

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Authors and Affiliations

  1. Department of Pharmacy and Pharmaceutical Technology and Parasitology, University of Valencia, Avenida Vicente Andres Estelles SN, 46100, Burjassot, Valencia, Spain

    Juan J Carreras, Willian E Tapia-Ramirez, Adrian Sala, Antonio J Guillot, Teresa M Garrigues & Ana Melero

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  1. Juan J Carreras
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  2. Willian E Tapia-Ramirez
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  3. Adrian Sala
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  4. Antonio J Guillot
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  6. Ana Melero
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Correspondence to Ana Melero.

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The skin permeability study was approved by the Ethical Committee of the University of Valencia, under the protocol number: H1381683846659. Abdominal skin was obtained from female patients, after signed informed consent.

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Carreras, J.J., Tapia-Ramirez, W.E., Sala, A. et al. Ultraflexible lipid vesicles allow topical absorption of cyclosporin A. Drug Deliv. and Transl. Res. 10, 486–497 (2020). https://doi.org/10.1007/s13346-019-00693-4

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