Optical instrument for measurement of vaginal coating thickness by drug delivery formulations

Abstract

An optical device has been developed for imaging the human vaginal epithelial surfaces, and quantitatively measuring distributions of coating thickness of drug delivery formulations—such as gels—applied for prophylaxis, contraception or therapy. The device consists of a rigid endoscope contained within a 27-mm-diam hollow, polished-transparent polycarbonate tube (150mm long) with a hemispherical cap. Illumination is from a xenon arc. The device is inserted into, and remains stationary within the vagina. A custom gearing mechanism moves the endoscope relative to the tube, so that it views epithelial surfaces immediately apposing its outer surface (i.e., 150mm long by 360° azimuthal angle). Thus, with the tube fixed relative to the vagina, the endoscope sites local regions at distinct and measurable locations that span the vaginal epithelium. The returning light path is split between a video camera and photomultiplier. Excitation and emission filters in the light path enable measurement of fluorescence of the sited region. Thus, the instrument captures video images simultaneously with photometric measurement of fluorescence of each video field [∼10mm diameter; formulations are labeled with 0.1%w∕w United States Pharmacoepia (USP) injectable sodium fluorescein]. Position, time and fluorescence measurements are continuously displayed (on video) and recorded (to a computer database). The photomultiplier output is digitized to quantify fluorescence of the endoscope field of view. Quantification of the thickness of formulation coating of a surface sited by the device is achieved due to the linear relationship between thickness and fluorescence intensity for biologically relevant thin layers (of the order of 0.5mm). Summary measures of coating have been developed, focusing upon extent, location and uniformity. The device has begun to be applied in human studies of model formulations for prophylaxis against infection with HIV and other sexually transmitted pathogens.