acyclovir and stearylamine

In this study, we demonstrated that cationic liposomes with incorporated stearylamine (SA) inhibit viral infectivity without preloaded active pharmaceutical ingredients. Specifically, we correlated physiochemical properties of liposomes, such as zeta potentials and particle sizes, with virus infectivity using the BacMam™ reagent, which is based on recombinant baculovirus (BV). Compared with neutral or negatively-charged liposomes, SA liposomes suppressed BV infectivity in several mammalian cell lines, including A549 cells. SA liposomes inhibited BV infection over 80% by optimizing the liposomal concentration and exposure time with cells. Moreover, these antiviral SA liposomes were not cytotoxic, and reducing the embedded cholesterol contents intensified the antiviral effects and simultaneously increased the binding of SA liposomes to the cell membranes. These data indicate that binding of SA liposomes to cell membranes may block virus entry. Finally, we also demonstrated the antiviral effects of SA liposomes on herpes simplex virus type 1 in A549 cells, and showed comparable efficacy to that of the antiviral drug acyclovir.

Topics: A549 Cells; Acyclovir; Amines; Animals; Antiviral Agents; Baculoviridae; Cations; Cell Survival; Chlorocebus aethiops; Herpesvirus 1, Human; Host-Pathogen Interactions; Humans; Liposomes; Vero Cells; Viral Plaque Assay; Virus Diseases

Design of a liposome delivery system for vaginal administration of acyclovir, able to provide sustained release and improved bioavailability of the encapsulated drug for the local treatment of genital herpes was investigated. Acyclovir was encapsulated in liposomes prepared by the polyol dilution method, whereby various phospholipid compositions were used: egg phosphatidylcholin (PC)/egg phosphatidylglycerol (PG) 9:1, egg phosphatidylcholine (PC) and egg phosphatidycholine (PC)/stearylamine (SA) 9:3. All liposome preparations were characterized and compared for particle size, polydispersity, encapsulation efficiency and tested for in vitro stability in different media chosen to simulate human vaginal conditions: buffer, pH 4.5 (corresponding to normal human vaginal pH), vaginal fluid simulant (medium developed so as to mimic the fluid produced in the vagina) with or without mucin. To be closer to in vivo application of liposomes and to achieve further improvement of their stability, liposomes were incorporated in a vehicle suitable for vaginal self-administration. Bioadhesive hydrogel made from Carbopol 974P NF resin with adequate pH value and desirable viscosity was chosen as a vehicle for liposomes containing acyclovir. In vitro release studies of liposomes incorporated in the hydrogel proved their applicability as a novel vaginal delivery system with localized and sustained release of encapsulated acyclovir. Even after 24 h of incubation in vaginal fluid simulant more than 35% of the originally encapsulated drug was retained in the hydrogel.

Topics: Acrylates; Acyclovir; Administration, Intravaginal; Amines; Antiviral Agents; Hydrogels; Liposomes; Phosphatidylcholines; Phosphatidylglycerols; Tissue Adhesives