Acyclovir is the gold standard drug for herpes simplex virus type 2 (HSV-2) infection treatment. Vaginal topical therapy with acyclovir is hampered due to its poor bioavailability, low retention at the vaginal mucosa, thus requiring high doses and frequent administrations. Nanocarriers have been proposed to overcome the challenges associated with antiviral delivery. This work aims at developing a novel formulation consisting of sulfobutyl ether-β-cyclodextrin decorated nanodroplets for acyclovir topical delivery to improve its antiviral effectiveness. To obtain acyclovir-loaded nanodroplets, the drug was previously complexed with sulfobutyl ether-β-cyclodextrin, and then incorporated in the nanodroplet chitosan shell via electrostatic interaction. The acyclovir-cyclodextrin inclusion complex was characterized by phase solubility, DSC, FTIR studies. The nanodroplets showed an average diameter of about 400 nm and positive surface charge. Acyclovir was efficiently incorporated in the nanodroplets (about 97% of encapsulation efficiency) and slowly released over time. The acyclovir-loaded nanodroplets exhibited an enhanced antiviral activity compared to the free drug against HSV-2 in cell cultures, which might be ascribed to a higher intracellular accumulation of the drug in nanodroplet-treated cells than in free acyclovir-treated cells. Based on these results, this new nanoformulation paves the way for the development of a future nanomicrobicide for the HSV-2 infections.
Manuela Donalisio, Monica Argenziano, Massimo Rittà, Chiara Bastiancich, Andrea Civra, David Lembo, Roberta Cavalli (2020) Acyclovir-loaded sulfobutyl ether-β-cyclodextrin decorated chitosan nanodroplets for the local treatment of HSV-2 infections, International Journal of Pharmaceutics, 587, 119676,