Bioactive Polymer Systems, Development of Microbicide Drug Delivery Systems, Technology to Advance Women

We are interested in the engineering, design and testing of polymeric and colloidal constructs that can be used in drug delivery applications. In particular we are interested in colloidal systems (e.g. soluble polymers and hydrogel particles), chemical reactions that allow polymer crosslinking to occur in the biological milieu and triggered drug delivery. When advantageous we take inspiration in our designs from the way nature has solved problems related to the assembly of materials in vivo and controlled delivery of endogenous factors. We are researching several biomimetic approaches in antiviral drug delivery systems and biologically inspired crosslinking reactions.

In particular we have directed our efforts on applying these principles to the design of vaginal drug delivery systems for the prevention of sexual transmitted diseases, also known as microbicides. Our focus is on the development of microbicides for the prevention of the sexual transmission of HIV. Women are much more susceptible to HIV infection than men and have no means of protecting themselves other than abstinence or negotiating condom use. The development of safe and effective microbicides is desperately needed in sub-Saharan Africa and elsewhere. As a part of the international effort in microbicide R&D, we are designing polymeric constructs integrating elements that respond to biological components in semen for the triggered release of anti-HIV drugs. The rationale for this route exploits the fact that semen introduces the infecting agent. Therefore we intend to use seminal components to trigger drug release from polymeric constructs present in the vagina before intercourse. In this way the active agents’ biodistribution and bioavailability can be modulated to increase potency and reduce the chance for viral resistance to develop. In our work we aim to apply contemporary designs of bioresponsive drug delivery systems and tailor these to the physiological and mechanical requirements essential for effective vaginal delivery.

Gupta KM, Pearce SM, Poursaid AE, Aliyar HA, Tresco PA, Mitchnik MA, Kiser PF, Polyurethane intravaginal ring for controlled delivery of dapivirine, a nonnucleoside reverse transcriptase inhibitor of HIV-1. J Pharm Sci 2008 Oct;97(10):4228-39

Gupta KM, Barnes SR, Tangaro RA, Roberts MC, Owen DH, Katz DF, Kiser PF, Temperature and pH sensitive hydrogels: an approach towards smart semen-triggered vaginal microbicidal vehicles. J Pharm Sci 2007 Mar;96(3):670-81

Endrizzi BJ, Huang G, Kiser PF, Stewart RJ, Specific covalent immobilization of proteins through dityrosine cross-links. Langmuir 2006 Dec 19;22(26):11305-10

Stayner RS, Min DJ, Kiser PF, Stewart RJ, Site-specific cross-linking of proteins through tyrosine hexahistidine tags. Bioconjug Chem 2005 Nov-Dec;16(6):1617-23

Oortgiesen M, Veronesi B, Eichenbaum G, Kiser PF, Simon S , Residual oil fly ash and charged polymers activate epithelial cells and nociceptive sensory neurons. Am J Physiol Lung Cell Mol Physiol 2000 Apr;278(4):L683-95

Kiser PF, Wilson G, Needham , A synthetic mimic of the secretory granule for drug delivery. Nature 1998 Jul 30;394(6692):459-62

Eichenbaum GM, Kiser PF, Simon SA, Needham , pH and Ion-Triggered Volume Response of Anionic Hydrogel Microspheres. Macromolecules 1998 Jul 28;31(15):5084-93