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.

Optical imaging and analysis of human vaginal coating by drug delivery gels

“…each data value could vary by ~10% from the actual thickness of undiluted gel). Also, the absolute error (limit of gel depth resolution) is 15 -25 μm [10]. This means that we cannot distinguish presence or absence of gel if it is as thin as 15 -25 μm.…”

“…A thorough description of the new instrument is presented in our introductory methods paper [10]. Here, we summarize salient operational features (see Fig.…”

“…Repeated calibrations using samples drawn from an aliquot of gel have given relatively invariant results for all gels tested. Values of σ(k)/k range from 0.02 -0.03 across gels [10].…”

“…We have developed a new, complementary technology to the remote sensing methods [10]. This endoscope-based device is inserted into the vagina and images the epithelial surfaces under conditions that simulate intromission.…”

In vivooptical imaging of human vaginal gel thickness distributions with a probe-based, dual-modality instrument

“…Data from this device can be input to biophysical models of coating layers development and of HIV transport. [7][8][9]16 We initially created a fluorescence-based device, 17,18 but the addition of an exogenous contrast agent (sodium fluorescein) limited the time interval for imaging because of separation of the fluorophore from gel to tissue.…”