title: Utilization of nanotechnology to enhance percutaneous absorption of acyclovir in the treatment of herpes simplex viral infections.
abstract: This study aimed to formulate an optimized acyclovir (ACV) nanoemulsion hydrogel in order to provide a solution for the slow, variable, and incomplete oral drug absorption in patient suffering from herpes simplex viral infection. Solubility of ACV in different oils, surfactants, and cosurfactants was explored utilizing a cubic model mixture design to obtain a nanoemulsion with minimum globule size. Preparation of an optimized ACV nanoemulsion hydrogel using a three-factor, three-level Box-Behnken statistical design was conducted. The molecular weight of chitosan (X1), percentage of chitosan (X2), and percentage of Eugenol as a skin permeation enhancer (X3) were selected to study their effects on hydrogel spreadability (Y1) and percent ACV permeated through rat skin after 2.5 hours (Y2). A pharmacokinetic study of the optimized ACV nanoemulsion hydrogel was conducted in rats. Mixtures of clove oil and castor oil (3:1 ratio), Tween 80 and Span 80 (3:1 ratio), and propylene glycol and Myo-6V (3:1 ratio) were selected as the oil, surfactant, and cosurfactant phases, respectively. Statistical analysis indicated that the molecular weight of chitosan has a significant antagonistic effect on spreadability, but has no significant effect on the percent ACV permeated. The percentage of chitosan also has a significant antagonistic effect on the spreadability and percent ACV permeated. On the other hand, the percentage of Eugenol has a significant synergistic effect on percent ACV permeated, with no effect on spreadability. The ex vivo study demonstrated that the optimized ACV nanoemulsion hydrogel showed a twofold and 1.5-fold higher permeation percentage than the control gel and marketed cream, respectively. The relative bioavailability of the optimized ACV nanoemulsion hydrogel improved to 535.2% and 244.6% with respect to the raw ACV hydrogel and marketed cream, respectively, confirming improvement of the relative bioavailability of ACV in the formulated nanoemulsion hydrogel.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Mutlaq M
authors.initials: MM
authors.lastname: Al-Subaie
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni Suef University, Beni Suef, Egypt.
authors.forename: Khaled M
authors.initials: KM
authors.lastname: Hosny
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Khalid Mohamed
authors.initials: KM
authors.lastname: El-Say
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia ; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Ahmed
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Bader M
authors.initials: BM
authors.lastname: Aljaeid
mesh_terms: D000212:Acyclovir / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D048271:Chitosan / Q000032:analysis / Q000493:pharmacokinetics; D005054:Eugenol / Q000032:analysis / Q000493:pharmacokinetics; D006561:Herpes Simplex / Q000188:drug therapy*; D020100:Hydrogels / Q000737:chemistry; D008297:Male; D008962:Models, Theoretical; D008970:Molecular Weight; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*
chemical_list: D020100:Hydrogels; D005054:Eugenol; D048271:Chitosan; D000212:Acyclovir
keywords: acyclovir; experimental design; hydrogel; nanoemulsion; optimization; relative bioavailability