Polymeric Electrospun Fibrous Dressings for Topical Co-delivery of Acyclovir and Omega-3 Fatty Acids

Tiago Costa; Artur Ribeiro; Raul Machado; Clarisse Ribeiro; Senentxu Lanceros-Mendez; Artur Cavaco-Paulo; Andreia Almeida; José das Neves; Marlene Lúcio; Teresa Viseu

doi:10.3389/fbioe.2019.00390

Polymeric Electrospun Fibrous Dressings for Topical Co-delivery of Acyclovir and Omega-3 Fatty Acids

Front Bioeng Biotechnol. 2019 Dec 3:7:390. doi: 10.3389/fbioe.2019.00390. eCollection 2019.

Authors

Tiago Costa¹, Artur Ribeiro², Raul Machado^{3

4}, Clarisse Ribeiro^{1

2}, Senentxu Lanceros-Mendez^{1

5

6}, Artur Cavaco-Paulo², Andreia Almeida^{7

8

9}, José das Neves^{7

8}, Marlene Lúcio^{1

3}, Teresa Viseu¹

Affiliations

¹ Centre of Physics of Universities of Minho and Porto (CF-UM-UP), University of Minho, Braga, Portugal.
² Centre of Biological Engineering (CEB), University of Minho, Braga, Portugal.
³ Centre of Molecular and Environmental Biology (CBMA), University of Minho, Braga, Portugal.
⁴ Institute of Science and Innovation for Sustainability (IB-S), University of Minho, Braga, Portugal.
⁵ Basque Center for Materials, Applications and Nanostructures (BCMaterials), UPV/EHU Science Park, Leioa, Spain.
⁶ Basque Foundation for Science (Ikerbasque), Bilbao, Spain.
⁷ Institute for Research and Innovation in Health (i3S), University of Porto, Porto, Portugal.
⁸ Institute of Biomedical Engineering (INEB), University of Porto, Porto, Portugal.
⁹ Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Porto, Portugal.

Abstract

Herpetic infections caused by Herpes simplex virus (HSV) are among the most common human infections, affecting more than two quarters of the world's population. The standard treatment for orofacial herpes is the administration of antiviral drugs, mainly acyclovir (ACV). However, current products are mostly based on semisolid formulations that have limited ability to promote drug skin penetration and tend to leak from the application site, thus showing reduced ability to sustain local drug residence. This work reports on the production of poly (ε-caprolactone) (PCL) fibrous matrices with ACV and omega-3 fatty acids (ω3) for application as dressings to the topical treatment of orofacial herpes. PCL fibrous matrices with the co-incorporated bioactive compounds were obtained by electrospinning and characterized regarding their morphology, chemical, physical, and mechanical properties. The potential use of the developed polymeric fibrous matrices for topical applications was evaluated by: (i) the release kinetics of the bioactive compounds; (ii) the occlusive factor of the fibrous mat; (iii) ACV skin permeation capacity; and (iv) the cytotoxicity in a keratinocyte cell line. PCL fibrous matrices loaded with the bioactive compounds presented a smooth morphology and a good balance between flexibility and hardness essential to be durable for handling, while having a desirable texture to be used comfortably. The fibrous mat also provided a sustained release of ACV during 96 h and improved the skin permeability of this drug (Kp = 0.00928 ± 0.000867 cm/h) presenting also high porosity (74%) and a water vapor transmission rate (WVTR) of 881 ± 91 g/m²day, essential to maintain moist and oxygen for faster healing of herpes lesions. Furthermore, cytotoxicity studies suggest that the fibrous mat are safe for topical application. Overall, the PCL based electrospun fibrous matrices with ACV and ω3 hereby described have the potential to be used as therapeutic bandage systems for the treatment of orofacial herpes.

Keywords: acyclovir; electrospinning; omega-3 fatty acids; poly (ε-caprolactone); polymeric fibrous dressings.