Prevention of
sexually transmitted infections is a priority in developed and developing countries. One approach to prevention is the use of
topical microbicides, and one promising approach is the use of
dendrimers, highly branched macromolecules synthesized from a polyfunctional core. Three new
dendrimer products developed to provide stable and cost-efficient
microbicides were initially evaluated in vitro for anti-herpes simplex virus activity and then in vivo by using a mouse model of
genital herpes. From these experiments one product,
SPL7013, was chosen for further evaluation to define the dose and duration of protection. Unformulated
SPL7013 provided significant protection from
genital herpes disease and
infection at concentrations as low as 1 mg/ml and for at least 1 h following topical (
intravaginal) administration of 10 mg/ml. This compound was then formulated into three vehicles and further evaluated in mouse and guinea pig models of
genital herpes infection. In the murine evaluations each of the formulations provided significant protection at concentrations of 10 and 50 mg/ml. Formulated compounds provided protection for at least 1 h at a concentration of 10 mg/ml. From these experiments formulation 2V was chosen for dose ranging experiments using the guinea pig model of
genital herpes. The guinea pig evaluations suggested that doses of 30 to 50 mg/ml were required for optimal protection. From these studies a lead compound and formulation (2V of
SPL7013) was chosen for ongoing evaluations in primate models of simian immunodeficiency virus and Chlamydia trachomatis
infection.