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.
Highlights
Herpes are a group of infectious diseases very common in humans, caused by direct exposure to the Herpesviridae family viruses or through contact with objects contaminated with these viruses (Mustafa et al, 2016)
In view of the successful attempts to load ACV in polymeric fibers, we propose the development of PCL fibrous matrices, prepared by electrospinning, to be used as dressings for the topical delivery of ACV and fish oils rich in omega-3 fatty acids (ω3)
The PCL fibrous matrix is constituted by randomly oriented fibers with a smooth surface, a cylindrical morphology (Figure 2A, PCL) and an average diameter of 1.8 ± 0.7 μm (Figure 2B, PCL)
Summary
Herpes are a group of infectious diseases very common in humans, caused by direct exposure to the Herpesviridae family viruses or through contact with objects contaminated with these viruses (Mustafa et al, 2016). Infections caused by HSV are one of the most common human diseases affecting 60–95% of the world’s population (Jiang et al, 2016) These viral agents are responsible for a wide range of pathologies that range from simple, treatable genito-facial, and orofacial lesions (gingivostomatitis, herpes labialis and genital herpes) to more severe infections affecting the eyes (keratoconjunctivitis) and central nervous system (herpetic encephalopathy and meningitis) (Javad et al, 2014; Lopes et al, 2018). As compared with oral administration, topical administration of ACV leads to 10-fold higher concentration over the entire epidermis (Jain et al, 2011) This concentration fails to produce the desired therapeutic effect at the site of infection because of the low penetration of ACV in the basal epidermis (Lembo and Cavalli, 2010; Jain et al, 2011). It is evident the need to develop alternative systems that allow a better distribution of ACV and its topical delivery in a more convenient way to minimize therapeutic failure (Lopes et al, 2018)
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