Enhanced vaginal drug delivery through the use of hypotonic formulations that induce fluid uptake.
نویسندگان
چکیده
Mucosal epithelia use osmotic gradients for fluid absorption and secretion. We hypothesized that administration of hypotonic solutions would induce fluid uptake that could be advantageous for rapidly delivering drugs through mucus to the vaginal epithelium. We found that hypotonic formulations markedly increased the rate at which small molecule drugs and mucoinert nanoparticles (mucus-penetrating particles, or MPP), but not conventional mucoadhesive nanoparticles (CP), reached the vaginal epithelial surface in vivo in mice. Additionally, hypotonic formulations greatly enhanced drug and MPP delivery to the entire epithelial surface, including deep into the vaginal folds (rugae) that drugs or MPP in isotonic formulations failed to reach efficiently. However, hypotonic formulations caused unencapsulated "free" drugs to be drawn through the epithelium, reducing vaginal retention. In contrast, hypotonic formulations caused MPP to accumulate rapidly and uniformly on vaginal surfaces, ideally positioned for localized sustained drug delivery. Using a mouse model of vaginal genital herpes (HSV-2) infection, we found that hypotonic delivery of free drug led to improved immediate protection, but diminished longer-term protection. In contrast, as we previously demonstrated, hypotonic delivery of drug via MPP led to better long-term retention and protection in the vagina. Importantly, we demonstrate that slightly hypotonic formulations provided rapid and uniform delivery of MPP to the entire vaginal surface, thus enabling formulations with minimal risk of epithelial toxicity. Hypotonic formulations for vaginal drug delivery via MPP may significantly improve prevention and treatment of reproductive tract diseases and disorders.
منابع مشابه
Docetaxel delivery using folate-targeted liposomes: in vitro and in vivo studies
Objective(s): Folate-targeted liposomes have been well considered in folate receptor (FR) overexpressing cells including MCF-7 and 4T1 cells in vitro and in vivo. The objective of this study is to design an optimum folate targeted liposomal formulations which show the best liposome cell uptake to tumor cells.Material and Methods: In this study, we prepared and characterized different targ...
متن کاملDevelopment and Characterization of Bioadhesive Gel of Microencapsulated Metronidazole for Vaginal Use
The present study concerned with the development and characterization of metronidazole microcapsules prepared by thermal change method using different ratios (1:1, 1:2 and 1:4) of ethyl cellulose in order to select the best microcapsule formulation with a good encapsulation efficiency and drug release profile. The obtained microcapsules were discrete, spherical with free flowing properties and ...
متن کاملDevelopment and Characterization of Bioadhesive Gel of Microencapsulated Metronidazole for Vaginal Use
The present study concerned with the development and characterization of metronidazole microcapsules prepared by thermal change method using different ratios (1:1, 1:2 and 1:4) of ethyl cellulose in order to select the best microcapsule formulation with a good encapsulation efficiency and drug release profile. The obtained microcapsules were discrete, spherical with free flowing properties and ...
متن کاملEnhanced Transdermal Delivery of Granisetron by Using Iontophoresis
The purpose of the present study was to explore the passive and electrically assisted transdermal transport of Granisetron hydrochloride (GRA) in solution and gel formulation through iontophoresis and also the feasibility of delivering therapeutic amounts of drug for the treatment of chemotherapy-induced nausea and vomiting. In this study, iontophoretic permeation of GRA through guinea pig...
متن کاملChitosan and Kappa-Carrageenan Vaginal Acyclovir Formulations for Prevention of Genital Herpes. In Vitro and Ex Vivo Evaluation
Vaginal formulations for the prevention of sexually transmitted infections are currently gaining importance in drug development. Polysaccharides, such as chitosan and carrageenan, which have good binding capacity with mucosal tissues, are now included in vaginal delivery systems. Marine polymer-based vaginal mucoadhesive solid formulations have been developed for the controlled release of acycl...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Biomaterials
دوره 34 28 شماره
صفحات -
تاریخ انتشار 2013