Abstract
Curcumin is a dietary compound with accrued evidence of antiviral activity. Poor solubility and permeation renders curcumin a good applicant for incorporation into proniosomes. The intent of this study was to formulate curcumin proniosomal gel for topical application and the evaluation of its in-vitro, ex-vivo activities against Herpes Simplex virus type 1 (HSV-1), as well as molecular docking studies on HSV-1 thymidine kinase proteins. Coacervation phase separation tactic, using 23 full factorial design, was used in the preparation of different proniosomes. Cytotoxicity of the selected formulae (F4 and F8) was evaluated on the Vero cell line. Optimal formulae (F4 and F8) showed entrapment efficiency of 97.15 ± 2.47% and 95.85 ± 2.9%, vesicle size of 173.7 ± 2.26 nm and 206.15 ± 4.17 nm and percentages curcumin released after 3 h of 51.9 ± 1.4% and 50.5 ± 1.1%, respectively. Ex-vivo permeation studies demonstrated that the optimal formulae markedly improved the dermal curcumin delivery. Curcumin proniosomal gel formulae exhibited 85.4% reduction of HSV-1 replication. The ability of curcumin to interact with the key amino acids in the enzyme binding sites of 1KI7, 1KI4, and 1E2P, as indicated by its docking pattern, rationalized its observed activity. Therefore, curcumin proniosomes could be considered as a successful topical delivery system for the treatment of HSV-1.
Highlights
Herpes simplex virus type 1 (HSV-1) is a highly contagious pathogen, which is common and endemic throughout the world
Curcumin proniosomes could be considered as a successful topical delivery system for the treatment of HSV-1
Local treatment with acyclovir is seemingly regarded as the topical therapy standard [3]
Summary
Herpes simplex virus type 1 (HSV-1) is a highly contagious pathogen, which is common and endemic throughout the world. Its ability to institute latency leads to the chronic nature of herpes infection where symptoms may periodically recur in the form of outbreaks of herpetic sores manifesting as burning, watery blisters in the skin or mucous membranes in the mouth and lips [2]. Local treatment with acyclovir is seemingly regarded as the topical therapy standard [3]. The cornerstone of antiviral therapy has been nucleoside analogues such as acyclovir, which, when phosphorylated by viral thymidine kinase, inhibits the viral DNA polymerase by acting as a chain terminator. Combating viral diseases has always been challenging, due to rapid mutation in viral genetics, resulting in resistance to antiviral drugs. With most antivirals, side effects hinder their long-term administration [4]
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