Transport phenomena and pharmacokinetics of anti-HIV microbicide drug delivery
Başlık çevirisi mevcut değil.
- Tez No: 602046
- Danışmanlar: PROF. ANDREW J. SZERI
- Tez Türü: Doktora
- Konular: Mühendislik Bilimleri, Makine Mühendisliği, Engineering Sciences, Mechanical Engineering
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2011
- Dil: İngilizce
- Üniversite: Unıversıty Of Calıfornıa Berkeley
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: Belirtilmemiş.
Özet
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Özet (Çeviri)
Microbicides are agents that can be applied to vaginal mucosal surfaces with the goal of blocking the transmission of sexually transmitted pathogens including HIV. They can be formulated in various delivery vehicles, including gels, creams, lotions, tablets or lms. A recent study in South Africa has con rmed, for the rst time, that a vaginal gel formulation of the antiretroviral drug Tenofovir, when topically applied, signi cantly inhibits sexual HIV transmission to women. However the gel for this drug, and anti-HIV microbicide vehicles in general, have not been designed using an understanding of how their spreading and retention in the vagina govern successful drug delivery. Elastohydrodynamic lubrication theory can be applied to model spreading of microbicide gels and lms. This should incorporate the full rheological behavior, including how rheological properties change due to contact with, and dilution by, ambient vaginal uids. A Carreau-like non-Newtonian model is adopted as a rheological model. The e ects of three important factors, i.e., dilution by vaginal uid, a yield stress of the gel and swelling, are investigated. Dilution accelerates the coating ow by creating a slippery region near the vaginal wall akin to a dilution boundary layer. The concept of a yield stress uid is attractive because such a material may tend to stay in place after coating vulnerable surfaces. We show that the lubrication approximation, which eases the e orts of design, may be applied to the elastic wall-squeezing problem for a prototype gel with yield stress. For the important presence of signi cant swelling of the gel by absorption of vaginal uid, the model indicates more rapid coating. Then we study lms that can be preferable over gels due to several reasons in many parts of the world. A model is developed for transient swelling and spreading of a lm, and subsequent distribution of an active drug throughout the vaginal lumen. We investigate the e ects of combination of many factors. The theory developed here improves our understanding of the biophysics of microbicide gel and lm ows in vivo. Ultimately, this dissertation contributes to a methodology that provides objective evaluations of microbicide gel and lm performance and in the design of new, improved vehicles.
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