Background:Acyclovir (ACY) is effective in the treatment of herpes simplex (HSV-1) & (HSV-2) but has systemic toxic effects if given orally or intravenously. ACY has not been used to treat the disease topically due to poor drug penetration into skin. A novel 1% liposomal ACY topical gel in a 5% Hydroxypropylmethyl cellulose (HPMC) K4M gel base has been developed and clinically evaluated in HSV-1 and HSV-2 patients.Material/Methods:26 patients suffering from recurrent mild facial (HSV-1) and genital (HSV-2) infections (HSV-1: 4F, 6M, age 21–34 years; HSV-2: 16M, age 24–40 years) were subjected to double blind clinical evaluation. Plain ACY gel (PAG) and Liposomal ACY gel (LAG) were clinically evaluated by application five times daily on herpetic lesions for up to eight weeks.Results:A significant increase in the average percent improvement of lesion healing was observed in HSV-1 and HSV-2 patients after 2–3 weeks treatment with LAG, as well as a significant decrease in side effects associate with ACY, such as itching and burning in both HSV-1 and HSV-2, and burning micturation in HSV-2.Conclusions:The results demonstrate that a five-fold reduction in the ACY content in liposomal gel is sufficient for the complete healing of herpetic lesions in HSV-1 and HSV-2 infection. The increased duration of topical therapy may be acceptable for patients suffering from mild herpetic lesions because of the advantage of avoiding systemic and local side effects

Keywords: acyclovir, Herpes Simplex, clinical studies, Liposomes