Pain, obesity, and physical function in Mexican American older adults during 20 years of follow-up.

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.

Sustained Intracellular Raltegravir Depots Generated with Prodrugs Designed for Nanoparticle Delivery.

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.