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Pasadena, CA, United States

Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 211.86K | Year: 2013

DESCRIPTION (provided by applicant): The broad long-term of this project is to develop methods for evaluation of adherence to intravaginal microbicide therapy for the prevention of HIV transmission. Correct determination of adherence to preventative therapies in clinical trials is essential to accurate evaluation of efficacy. A better understanding of the true adherence to a preventative therapy will lead to the development of products with higher acceptability, and provide insight into the relationship between self-reported use of preventative therapy and actual use. Current methods of adherence evaluation for vaginal microbicide trials include self-reporting by study participants, physician or health care provider assessment, and inspection of study materials (gel applicators or used intravaginal rings) returned during clinic visits. All of these methods are prone to inaccuracy as indicated by the over-reporting of adherence observed in several clinical trials when adherence metrics were compared to trial outcomes. The proposed adherence-monitoring intravaginal ring (adherence IVR) will allow the direct measurement of adherence to IVR-delivered microbicide therapy by monitoring IVR temperature, conductivity, or both continuously on a half-hourly to hourly timescale to determine if the IVR is being worn or not during a clinical trial. The adherence IVR will contain a miniaturized module for sensing temperature (IVR at body temperature when in and below when out) and conductivity (IVR wetted and conductivity high when in, IVR dry and conductivity low when out) to determine adherence state. A microcontroller circuit embedded completely in the silicone ring structure will process the sensor data and store a digital adherence state (1 = IVR in, 0 = IVR out) to non-volatile memory at a fixed time interval. When the ring is removed, typically monthly, the adherence data may be downloaded from the IVR to a laptop computer or other device (smart phone or tablet) to provide a record of adherence that is free from reporting bias. The project has three principal objectives: (1) development of the microcontroller and sensor electronics and embedded software for sensor signal processing, conversion to digital adherence values, and logging to non-volatile memory for subsequentretrieval; (2) incorporation of this adherence monitoring functionality into a pod-IVR for intravaginal delivery of the microbicide tenofovir; and (3) evaluation of adherence monitoring performance, preliminary safety, and pharmacokinetics of tenofovir delivery in a sheep model. At the conclusion of this Phase I effort, a novel method for evaluating adherence to IVR microbicide therapy for prevention of HIV transmission will have been designed, fabricated, and evaluated in an animal model. The adherence-monitoring technology developed here may be extended to other pod-IVR delivery devices (i.e. microbicide combinations) and other IVR platforms. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: This project aims to develop a novel method for assessing adherence to intravaginal ring (IVR)-based microbicide therapy for the prevention of HIV transmission in clinical trial settings. The proposed adherence IVR will utilize measurement of temperatore, conductivity, or both in combination to determine if the ring is being worn or not, and to log a continuous, digital record of adherence determination for subsequent retrieval at the study conclusion.

A method of identifying a biofilm that includes non-typeable

Churchman S.A.,Auritec Pharmaceuticals, Inc. | Moss J.A.,Oak Crest Institute of Science | Baum M.M.,Oak Crest Institute of Science
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2016

An ion chromatographic method with conductivity detection for the precise and accurate analysis of lithium ions in phosphate-buffered saline, used as a cervicovaginal lavage (CVL) fluid, was developed and validated. The lithium ion dilution factor during the CVL is used to calculate the volume of cervicovaginal fluid (CVF) collected. Initial CVL Li+ concentrations of 1 mM and 10 mM were evaluated. The method is robust, practical, and afforded an accurate measurement (5% of the measurement, or better) at 24 μL of vaginal fluid simulant collected per mL of CVL fluid, as low as 5 μL mL-1 using 10 mM Li+ with a measurement accuracy of 6.7%. Ion chromatograms of real-world CVL samples collected in vivo from common animal models (sheep and pig-tailed macaque) and a human volunteer demonstrate that the analysis is interference-free. The method is readily transferrable and should enable the accurate measurement of CVF volume collected during CVLs benefitting a broad range of research disciplines, including pharmacokinetic, pharmacodynamic, metabolomic, and microbiome studies. © 2016.

Cortez J.M.,Auritec Pharmaceuticals, Inc. | Quintero R.,Auritec Pharmaceuticals, Inc. | Moss J.A.,Oak Crest Institute of Science | Beliveau M.,Pharsight | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

Mother-to-child transmission (MTCT) of HIV-1 remains a global health problem. The World Health Organization (WHO) recommendations advise the administration of a once-daily, oral, prophylactic regimen of the nonnucleoside reverse transcriptase inhibitor nevirapine (NVP) from birth until 4 to 6 weeks of age for infants born to HIV-infected mothers in regions without access to safe and nutritionally adequate alternatives to breast milk. A critical factor driving the successful implementation of the WHOguidelines involves sustaining high adherence to the frequent dosing. With these challenges in mind, we have developed the first injectable, sustained-release NVP formulations with the goal of providing, for 6 weeks or longer, preventative plasma drug levels from a single subcutaneous administration at birth. The long-acting NVP consists of large (>50 μm), monodisperse NVP particles coated with biocompatible polymers that control the drug release kinetics. Two lead formulations exhibiting burst-free, sustained-release kinetics for up to 75 days in vitro were developed. Subsequent in vivo studies in rats demonstrated no toxicity related to the formulations. Rat plasma NVP concentrations were above the analytical assay's limit of quantification for up to 28 days. Pharmacokinetic analysis of the rat plasma NVP concentration-time data allowed absorption rate constants to be calculated. These data then were used to simulate infant NVP exposure from a single injected dose (<200 mg) of our longacting formulations, demonstrating preliminary feasibility of the technology to maintain safe, preventative NVP plasma levels (0.2 to 3.0 μgml-1) for 6 weeks or longer. © 2015 American Society for Microbiology. All Rights Reserved.

Hoffmann M.R.,California Institute of Technology | Moss J.A.,Oak Crest Institute of Science | Baum M.M.,Oak Crest Institute of Science
Dalton Transactions | Year: 2011

Carbon dioxide is an appealing renewable feedstock for industrial chemical processes. This does not mean, however, that all chemical processes using CO2 are environmentally-friendly. Perspectives on the sustainability of CO2 utilization and artificial photosynthesis are provided. The discussions focus on the photocatalytic production of Cx (x ≥ 2) compounds, where all the carbon in the products is derived from CO2. This area of research, while promising, has received far less attention than analogous systems leading to C1 products. © 2011 The Royal Society of Chemistry.

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