Polymeric nanocarriers have been extensively used to improve the delivery of hydrophobic drugs, but often provide low encapsulation efficiency and percent loading for hydrophilic compounds. In particular, insufficient loading of hydrophilic antiretroviral drugs such as the integrase inhibitor raltegravir (RAL) has limited the development of sustained-release therapeutics or prevention strategies against HIV. To address this, we developed a generalizable prodrug strategy using RAL as a model where loading, release and subsequent hydrolysis can be tuned by promoiety selection. Prodrugs with large partition coefficients increased the encapsulation efficiency up to 25-fold relative to RAL, leading to significant dose reductions in antiviral activity assays. The differential hydrolysis rates of these prodrugs led to distinct patterns of RAL availability and observed antiviral activity. We also developed a method to monitor the temporal distribution of both prodrug and RAL in cells treated with free prodrug or prodrug-NPs. Results of these studies indicated that prodrug-NPs create an intracellular drug reservoir capable of sustained intracellular drug release. Overall, our results suggest that the design of prodrugs for specific polymeric nanocarrier systems could provide a more generalized strategy to formulate physicochemically diverse hydrophilic drugs with a number of biomedical applications.

According to the Alzheimer’s Association, 5.6 million Americans age 65 and older are living with Alzheimer’s Disease. Since pharmacological treatments have yet to be developed, we want to determine whether the amount and quality of social support influence the quality of life (QoL) of persons with dementia so they can lead active and purposeful lives. We analyzed data from 22,030 individuals aged 50+ from the 2010 Health and Retirement Study cohort. The dependent variable, QoL, was measured as self-rated health. The main independent variable, cognitive status, was obtained through direct and proxy interview measurements of cognition. For social support, a composite score including the number of social contacts/close relationships and perceived social support/strain was created. Lastly, several covariates were included. Longitudinally, we examined how QoL changed between 2010 and 2012 using 3 stepwise regression models. Model 1 found those with normal cognition have lower odds of poor QoL vs. those with cognitive impairment (OR = 0.38, p <.0001), number of relationships and perceived social support decreases the odds of poor QoL (p = 0.003, p <.0001), while social strain increases the odds of poor QoL (p <.0001). Model 3 revealed similar findings but also, persons with comorbidities have increased odds of poor QoL (p <.0001), while persons with better function have decreased odds of poor QoL (p <.0001). In conclusion, these results can be used to design interventions to improve social support and reduce social strain, which can also improve QoL for dementia caregivers.

Introduction Pain remains largely undertreated in older adults irrespective of health care setting. Mexican American adults in the United States have a high age‐adjusted prevalence of obesity. However, the association of pain and obesity with physical function is understudied in this population. Objective To examine the association of co‐occurring pain and obesity with physical function over 20 years of follow‐up in a cohort of older Mexican Americans who scored ≥7 (moderate to high) in the Short Physical Performance Battery (SPPB) test and were nondisabled at baseline. Design Longitudinal population‐based study. Setting Community‐dwelling older adults from Southwestern United States. Participants Mexican American adults age 65 years and older. Interventions Not Applicable. Main Outcome Measures Physical function was assessed with the SPPB test (standing balance, timed 8‐ft walk, and five repeated timed chair stands). Participants at baseline were divided into four groups: no pain–no obesity (n = 869), obesity only (n = 282), pain only (n = 216), and pain‐obesity (n = 159). Generalized Estimating Equation models were used to estimate the odds ratio (OR) and 95% confidence interval (CI) of lower performance in physical function over 20 years as a function of pain‐obesity grouping. Results Participants with pain only (OR = 1.61, 95% CI = 1.34–1.95) and with co‐occurring pain and obesity (OR = 2.32, 95% CI = 1.83–2.95) had significantly greater odds of physical function impairment over those with no pain–no obesity or obesity only, after controlling for all covariates. Conclusion Older Mexican American adults were at high risk for physical function impairment over time if they had pain or co‐occurring pain and obesity. Early assessment and proper pain management as well as maintaining a healthy weight may reduce declines in physical function in older Mexican American adults.