Mucus-penetrating drug carriers for vaginal drug delivery
Vaginal drug administration is a challenging approach due to the body´s natural defense mechanisms and specificity in formulation design. However, where applicable, topical drug delivery is preferable to systemic therapy. Firstly, it allows averting hepatic first pass effect and degradation by GI enzymes. Secondly, non-invasive application provides closer and direct contact with the affected area and relieves user from an unpleasant procedure. The aim of this project was development and optimization of mucus-penetrating liposomes for vaginal treatment of human papilloma virus (HPV). The naturally occurring protein interferon α-2b (IFN α-2b) is commonly used in treatment of vaginal infections. Due to continuous vaginal fluid renewal the residence time of mucoadhesive nanoparticles is shown to be insufficient. Treatment efficacy can be increased by designing novel, mucus-penetrating particles. To overcome the mucosal barrier, surface modification with the low molecular weight polymer polyethylene glycol (PEG), was applied. PEGylated liposomes containing IFN α-2b were prepared by thin film hydration method. Vesicle size was reduced by extrusion through polycarbonate membranes. Liposomal size, polydispersity, surface charge and IFN α-2b entrapment were determined. An adequate vesicle size (185 ± 3 nm) was obtained and a low polydispersity (PI 0.09) indicated a monodisperse size distribution. Net surface charge was measured to be -12.2 ± 1.4 mV. Free drug was separated from liposomally encapsulated IFN α-2b by gel column chromatography, and entrapment efficiency (88%) was determined using human IFN α ELISA kit. The newly developed system for local IFN α-2b delivery has a potential to treat HPV infections.
PublisherUiT Norges arktiske universitet
UiT The Arctic University of Norway
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