Fabrication of Anti-HSV-1 Curcumin Stabilized Nanostructured Proniosomal Gel: Molecular Docking Studies on Thymidine Kinase Proteins

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.

Statistical optimization of bile salt deployed nanovesicles as a potential platform for oral delivery of piperine: accentuated antiviral and anti-inflammatory activity in MERS-CoV challenged mice

“…Also the surfactants incorporated in the fabrication of the bilosomes have a crucial effect in enhancing piperine permeation across the viral cells (Badria et al, 2020 ). These results came in accordance with various studies that report the impact vesicular system as proniosomes in enhancing antiviral activity of curcumin against HSV (El-Halim et al, 2020 ). Additionally, selectivity index (SI) is computed by dividing the concentration of 50% cellular cytotoxicity to 50% effective concentration (SI = CC 50 /EC 50 ), denoting the comparative efficacy of a compound in viral replication inhibition to its cytopathic effect (Cong et al, 2018 ).…”

Development of Provesicular Nanodelivery System of Curcumin as a Safe and Effective Antiviral Agent: Statistical Optimization, In Vitro Characterization, and Antiviral Effectiveness

“…The antiviral activity of Curcumin was demonstrated by the molecular docking study to demonstrate the ability of Curcumin to bind effectively with the active site of DNA polymerase of HSV-1 [16,[94][95][96][97][98][99][100][101][102] (Figure S3) (Supplementary information). The antiviral activity of the reconstituted Curcumin-loaded proniosomal formula (F5) were tested and compared with that of Curcumin dispersion.…”

“…The antiviral activity of Curcumin against HSV could be attributed to interference with the metabolism of the virus through cell signaling and apoptosis [12,13,15]. However, the therapeutic applications of Curcumin have been hindered by its low aqueous solubility, low permeability, poor stability, and rapid in vivo degradation [16].…”

The Potential Synergistic Activity of Zolmitriptan Combined in New Self-Nanoemulsifying Drug Delivery Systems: ATR-FTIR Real-Time Fast Dissolution Monitoring and Pharmacodynamic Assessment

“…ZMT-SNEDDS were diluted 100 times in deionized water and gently shaken to create nanoemulsions prior to measurement. 15 …”