title: Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques.
abstract: The human immunodeficiency virus epidemic affects millions of people worldwide. As women are more vulnerable to infection, female-controlled interventions can help control the spread of the disease significantly. Glycerol monolaurate (GML), an inexpensive and safe compound, has been shown to protect against simian immunodeficiency virus infection when applied vaginally. However, on account of its low aqueous solubility, fabrication of high-dose formulations of GML has proven difficult. We describe the development of a vaginal cream that could be loaded with up to 35% GML. Vaginal drug levels and safety of 3 formulations containing increasing concentrations of GML (5%w/w, 15%w/w, and 35%w/w) were tested in rhesus macaques after vaginal administration. GML concentration in the vaginal tissue increased as the drug concentration in the cream increased, with 35% GML cream resulting in tissue concentration of ∼0.5 mg/g, albeit with high interindividual variability. Compared with the vehicle control, none of the GML creams had any significant effect on the vaginal flora and cytokine (macrophage inflammatory protein 3α and interleukin 8) levels, suggesting that high-dose GML formulations do not induce local adverse effects. In summary, we describe the development of a highly loaded vaginal cream of GML, and vaginal drug levels and safety after local administration in macaques.
authors.affiliation: Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Ameya R
authors.initials: AR
authors.lastname: Kirtane
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Meghan K
authors.initials: MK
authors.lastname: Rothenberger
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715.
authors.forename: Abby
authors.initials: A
authors.lastname: Frieberg
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715.
authors.forename: Karla
authors.initials: K
authors.lastname: Nephew
authors.affiliation: Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715.
authors.forename: Nancy
authors.initials: N
authors.lastname: Schultz-Darken
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
authors.affiliation: Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reimann
authors.affiliation: Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota 55455.
authors.forename: Ashley T
authors.initials: AT
authors.lastname: Haase
authors.affiliation: Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455. Electronic address: jpanyam@umn.edu.
authors.forename: Jayanth
authors.initials: J
authors.lastname: Panyam
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016207:Cytokines / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000517:prevention & control; D006801:Humans; D007848:Laurates / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D008253:Macaca mulatta; D050178:Monoglycerides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D012212:Rheology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000187:drug effects; D014621:Vagina / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D014622:Vaginal Creams, Foams, and Jellies / Q000009:adverse effects / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D007848:Laurates; D050178:Monoglycerides; D014622:Vaginal Creams, Foams, and Jellies; C020777:monolaurin
keywords: HIV/AIDS; drug delivery systems; formulation; global health; pharmacokinetics