Journal article
Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques
Journal of pharmaceutical sciences, Vol.106(7), pp.1821-1827
07/2017
DOI: 10.1016/j.xphs.2017.03.030
PMCID: PMC5511513
PMID: 28389267
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.
Details
- Title: Subtitle
- Evaluation of Vaginal Drug Levels and Safety of a Locally Administered Glycerol Monolaurate Cream in Rhesus Macaques
- Creators
- Ameya R Kirtane - Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455Meghan K Rothenberger - Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455Abby Frieberg - Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715Karla Nephew - Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715Nancy Schultz-Darken - Wisconsin National Primate Research Center, University of Wisconsin, Madison, Wisconsin 53715Thomas Schmidt - Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455Thomas Reimann - Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455Ashley T Haase - Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota 55455Jayanth Panyam - Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota 55455
- Resource Type
- Journal article
- Publication Details
- Journal of pharmaceutical sciences, Vol.106(7), pp.1821-1827
- DOI
- 10.1016/j.xphs.2017.03.030
- PMID
- 28389267
- PMCID
- PMC5511513
- NLM abbreviation
- J Pharm Sci
- ISSN
- 0022-3549
- eISSN
- 1520-6017
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 07/2017
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984001135702771
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