Identifying broken linkages coupling water availability and dryland urbanization for sustainability: The case of the Phoenix metropolitan region, USA.

One third of the world's largest cities are located in drylands, where much of future urbanization is projected to occur. This is paradoxical and unsustainable considering water scarcity in drylands, which is exacerbated by climate change. Thus, it is critical to better understand why and how dryland urbanization and water scarcity are decoupled so that sustainable measures can be designed. Focusing on the Phoenix Metropolitan Area (PMA) of the United States, we addressed the following questions: 1) What are the relative influences of water and economic factors on urbanization in recent decades? 2) Which linkages connecting water storage to urban development have been decoupled? and 3) How can water availability and development be better coupled to improve regional sustainability? We tested the relationships between economic factors, water availability, and urbanization, with Pearson Correlation Analysis and Structural Equation Modeling. We found that, from 1986 to 2019, urban population growth and urban land expansion in the PMA were driven by economic factors, and not influenced by fluctuations in water supply. We identified specific broken linkages among water storage, water deliveries, municipal water supply, and urbanization, which must be coupled to enforce water availability constraints on urban expansion in the context of climate change. Our study has important implications for dryland urban sustainability as urbanization on borrowed water is, by definition, unsustainable.

Simultaneous delivery of tenofovir and acyclovir via an intravaginal ring.

Vaginal microbicides may play an important role in protecting women from HIV infection. A strong synergy between HSV and HIV has been observed, and epidemiological studies demonstrate that HSV infection increases the risk of HIV acquisition. Incorporation of the antiretroviral tenofovir (TFV) along with the antiherpetic acyclovir (ACV) into combination intravaginal rings (IVRs) for sustained mucosal delivery of both compounds could lead to increased microbicide product adherence and efficacy compared with conventional vaginal formulations. A novel, dual-protection "pod IVR" platform developed in-house and delivering ACV and TFV was evaluated in rabbit and sheep models. The devices were safe and exhibited sustained release of both drugs independently and at controlled rates over the 28-day studies. Daily release rates were estimated based on residual drug content of the used devices: rabbits, 343 ± 335 µg day(-1) (ACV) and 321 ± 207 µg day(-1) (TFV); sheep, 174 ± 14 µg day(-1) (ACV) and 185 ± 34 µg day(-1) (TFV). Mean drug levels in sheep vaginal samples were as follows: secretions, 5.25 ± 7.31 µg ml(-1) (ACV) and 20.6 ± 16.2 µg ml(-1) (TFV); cervicovaginal lavage fluid, 118 ± 113 ng ml(-1) (ACV) and 191 ± 125 ng ml(-1) (TFV); tissue, 173 ng g(-1) (ACV) and 93 ng g(-1) (TFV). An in vitro-in vivo correlation was established for both drugs and will allow the development of future formulations delivering target levels for prophylaxis and therapy. These data suggest that the IVR based on the pod design has potential in the prevention of transmission of HIV-1 and other sexually transmitted pathogens.

Tenofovir and tenofovir disoproxil fumarate pharmacokinetics from intravaginal rings.

OBJECTIVES: To compare the distribution of tenofovir in sheep vaginal lumen, tissue, and plasma following topical delivery of the antiretroviral drug from intravaginal rings, either as tenofovir or the disoproxil fumarate prodrug. DESIGN: Comparative pharmacokinetic study in sheep. METHOD: Intravaginal rings formulated to achieve equivalent release rates of tenofovir and its disoproxil fumarate prodrug were evaluated for 28 days in sheep, with four animals in each group. Drug concentrations were measured by high-performance liquid chromatography-mass spectrometry. RESULTS: Tenofovir levels in cervicovaginal lavage were indistinguishable (P > 0.30) in both groups, but tissue levels in animals receiving the prodrug were 86-fold higher than those receiving tenofovir, and approximately 50 times higher than the level shown to be protective of HIV infection in the CAPRISA 004 trial. CONCLUSION: This is the first study to compare the pharmacokinetics of tenofovir and its disoproxil fumarate prodrug administered topically to the vaginal tract. These in-vivo data show that the prodrug leads to significantly higher drug tissue levels than tenofovir, a finding that may have important implications for the development of preexposure prophylaxis strategies based on topical delivery of antivirals to the female genital tract.