The aim of this project is to develop mucus-penetrating particles (MPP) that will improve microbicide delivery for protection against HIV and other STD pathogens such as HSV.
The aim of the R21 phase is to develop MPP to be tested in the R33 phase for protection against HIV in the humanized-BLT-SGlD mouse model. We have completed all of our negotiated milestones. Additionally, we present significant data that support our hypothesis that biodegradable MPP will provide improved protection against HIV and HSV when delivered vaginally once-a-day (non-coitally). We currently have biodegradable MPP that are ready for testing against HSV in our mouse model and against HIV in the humanized-BLT-SClD mouse model in the R33 phase of this project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33AI079740-05
Application #
8318249
Study Section
Special Emphasis Panel (NSS)
Program Officer
Veronese, Fulvia D
Project Start
2008-09-23
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$455,632
Indirect Cost
$128,425
Name
Johns Hopkins University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Maisel, Katharina; Reddy, Mihika; Xu, Qingguo et al. (2016) Nanoparticles coated with high molecular weight PEG penetrate mucus and provide uniform vaginal and colorectal distribution in vivo. Nanomedicine (Lond) 11:1337-43
Xu, Qingguo; Ensign, Laura M; Boylan, Nicholas J et al. (2015) Impact of Surface Polyethylene Glycol (PEG) Density on Biodegradable Nanoparticle Transport in Mucus ex Vivo and Distribution in Vivo. ACS Nano 9:9217-27
Maisel, Katharina; Ensign, Laura; Reddy, Mihika et al. (2015) Effect of surface chemistry on nanoparticle interaction with gastrointestinal mucus and distribution in the gastrointestinal tract following oral and rectal administration in the mouse. J Control Release 197:48-57
Maisel, Katharina; Chattopadhyay, Sumon; Moench, Thomas et al. (2015) Enema ion compositions for enhancing colorectal drug delivery. J Control Release 209:280-7
Ensign, Laura M; Cone, Richard; Hanes, Justin (2014) Nanoparticle-based drug delivery to the vagina: a review. J Control Release 190:500-14
Ensign, Laura M; Lai, Samuel K; Wang, Ying-Ying et al. (2014) Pretreatment of human cervicovaginal mucus with pluronic F127 enhances nanoparticle penetration without compromising mucus barrier properties to herpes simplex virus. Biomacromolecules 15:4403-9
Yang, Ming; Lai, Samuel K; Yu, Tao et al. (2014) Nanoparticle penetration of human cervicovaginal mucus: the effect of polyvinyl alcohol. J Control Release 192:202-8
Wang, Ying-Ying; Lai, Samuel K; Ensign, Laura M et al. (2013) The microstructure and bulk rheology of human cervicovaginal mucus are remarkably resistant to changes in pH. Biomacromolecules 14:4429-35
Ensign, Laura M; Hoen, Timothy E; Maisel, Katharina et al. (2013) Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake. Biomaterials 34:6922-9
Xu, Qingguo; Boylan, Nicholas J; Cai, Shutian et al. (2013) Scalable method to produce biodegradable nanoparticles that rapidly penetrate human mucus. J Control Release 170:279-86

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