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Development and characterization of a nanoemulsion containing propranolol for topical delivery

Authors Zanela da Silva Marques T, Santos-Oliveira R, Betzler de Oliveira de Siqueira L, Cardoso VS, Freitas ZMF, Barros RCSA, Villa ALV, Monteiro MSSB, Santos EP, Ricci-Junior E

Received 2 February 2018

Accepted for publication 17 March 2018

Published 14 May 2018 Volume 2018:13 Pages 2827—2837

DOI https://doi.org/10.2147/IJN.S164404

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Justinn Cochran

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J Webster

Tatiana Zanela da Silva Marques,1 Ralph Santos-Oliveira,2 Luciana Betzler de Oliveira de Siqueira,1 Verônica da Silva Cardoso,3 Zaida Maria Faria de Freitas,1 Rita de Cássia da Silva Ascenção Barros,1 Ana Lúcia Vazquez Villa,1 Mariana Sato de Souza de Bustamante Monteiro,1 Elisabete Pereira dos Santos,1 Eduardo Ricci-Junior1

1Department of Drugs and Medicines, Faculty of Pharmacy, 2Institute of Nuclear Energy, 3Unit of Biocatalysis, Bioproducts and Bioenergy (Bioinivar), Institute of Microbiology Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil

Background: Propranolol (PPN) is a therapeutic option for the treatment of infantile hemangiomas. This study aimed at the development of nanoemulsion (NE) containing 1% PPN, characterization of the system, and safety studies based on ex vivo permeation, cytotoxicity, and biodistribution in vivo.
Methods: The formulation was developed and characterized in relation to the droplet size, polydispersity index (PDI), pH, zeta potential, and electronic microscopy. Ex vivo permeation studies were used to evaluate the cutaneous retention of PPN in the epidermis and dermis. Cytotoxicity studies were performed in fibroblasts, macrophages, and keratinocytes. In vivo biodistribution assay of the formulations was performed by means of labeling with technetium-99m.
Results: NE1 exhibited droplet size of 26 nm, PDI <0.4, pH compatible with the skin, and zeta potential of −20 mV, which possibly contributes to the stability. Electron microscopy showed that the NE presented droplets of nanometric size and spherical shape. NE1 provided excellent stability for PPN. In the ex vivo cutaneous permeation assay, the NE provided satisfactory PPN retention particularly in the dermis, which is the site of drug action. In addition, NE1 promoted cutaneous permeation of the PPN in small amount. In vivo biodistribution showed that the radiolabeled formulation remained in the skin and a small amount reached the bloodstream. NE1 presented low cytotoxicity to fibroblasts, macrophages, and keratinocytes in the concentrations evaluated in the cytotoxicity assay.
Conclusion: We concluded that the formulation is safe for skin administration; however, cutaneous irritation studies should be performed to confirm the safety of the formulation before clinical studies in patients with infantile hemangiomas.

Keywords: infantile hemangiomas, nanoemulsion, propranolol, ex vivo permeation studies, cytotoxicity

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