Momentary effects of life stressors on mindfulness and emotion regulation difficulties among adolescents exposed to chronic stressors.

Adolescents faced with chronic stressors (e.g., financial instability, interpersonal violence) are at heightened risk for developing mental health problems, likely due in part to stressors that interfere with effective emotion regulation. Although mindfulness may help to act as a buffer against the deleterious effects of life stressors, a relatively untested assumption is that adolescents can maintain mindfulness during periods of stress. This paper explores this assumption by investigating the real-time, dynamic relationships among life stressors, mindfulness, and emotion regulation difficulties among adolescents exposed to chronic stressors. Eighty-one participants who were 10-18 years old (M = 14.33; SD = 2.20; 56% male; 57% Non-Hispanic White) completed ecological momentary assessments (EMA) three times a day for 7 days and contributed a total of 1186 EMA reports. Multilevel structural equation modelling revealed that the presence (vs. absence) of stressors was associated with lower momentary mindfulness and greater momentary emotion regulation difficulties concurrently and prospectively. Stressors with greater severity were also concurrently, but not prospectively, associated with lower momentary mindfulness and greater momentary emotion regulation difficulties. Findings highlight that exposure to life stressors may degrade momentary mindfulness and emotion regulation. Given that mindfulness and emotion regulation are closely associated with mental health, these results also demonstrate one way that stressors may contribute to health disparities at the micro-level. Going forward, it will be important to investigate methods of helping adolescents learn to maintain mindfulness and adaptive emotion regulation in the face of stressful events. This study was preregistered (NCT04927286).

Daily mindfulness, negative affect, and eating behaviors in adolescents at risk for excess weight gain.

OBJECTIVE: Loss-of-control and overeating are common in adolescents with high body mass index (BMI). Mindfulness may affect negative affect, and both may relate to loss-of-control and overeating. Yet, there is limited understanding of these associations in adolescents' daily lives. METHODS: Forty-five adolescents (77% female; Mage = 14.4 years, SDage = 1.7 years) with high weight (92% with BMI [kg/m2 ] ≥85th percentile for age/sex) provided daily, repeated measurements of mindfulness, negative affect, loss-of-control, and overeating for ~7 days (M = 5.6 days; range = 1-13). Multilevel mixed modeling was conducted to test within-person (intraindividual) and between-person (interindividual) associations for the same-day (concurrent) and next-day (time-ordered/prospective). RESULTS: There were within-person and between-person associations of higher mindfulness with lower negative affect on the same-day and next-day. Greater between-person mindfulness related to lower odds of adolescents' loss-of-control occurrence (same-day) and conversely, more perceived control over eating (same-day and next-day). Greater within-person mindfulness related to less odds of next-day overeating. DISCUSSION: Dynamic relations exist among mindfulness, negative affect, and eating in adolescents at-risk for excess weight gain. Mindfulness may be an important element to consider in loss-of-control and overeating. Future work using momentary-data within an experimental design would help disentangle the intraindividual effects of increasing mindfulness/decreasing negative affect on disordered eating. PUBLIC SIGNIFICANCE: Loss-of-control and overeating are common in teenagers with high weight. Greater mindfulness-present-moment, non-judgmental attention-and less negative emotions may relate to healthier eating, but we do not know how these processes play out in teenagers' daily lives. Addressing this knowledge gap, the current findings showed that greater daily mindfulness, but not negative affect, related to less loss-of-control/overeating, suggesting the importance of mindfulness for eating patterns in teenagers' daily lives.

Observations of parent-adolescent interactions relate to food parenting practices and adolescent disordered eating in adolescents at risk for adult obesity.

Adolescent disordered eating and obesity are interrelated and adversely relate to mental and metabolic health. Parental feeding practices have been associated with adolescent disordered eating and obesity. Yet, observable interactions related to food parenting have not been well characterized. To address this gap, N = 30 adolescents (M ± SD 14 ± 2 year) at risk for adult obesity due to above-average body mass index (BMI ≥70th percentile) or parental obesity (BMI ≥30 kg/m2 ) participated in a video-recorded parent-adolescent task to discuss a food/eating-related disagreement. Interactions were coded for individual/dyadic affect/content using the Interactional Dimensions Coding System. We examined associations of interaction qualities with parent-reported food practices, adolescent disordered eating behaviors/attitudes, and insulin resistance. Reported parenting practices were correlated with multiple interaction qualities (p-values <0.05), with the most consistent correspondence between parent-reported pressure to eat (e.g., pressure to eat more healthy foods) and negative aspects of parent-adolescent interactions. Also, after accounting for adolescent age, sex, and BMI-standard score, parent-adolescent interaction qualities were associated with adolescents' disordered eating and insulin resistance. Specifically, greater adolescent problem-solving related to less adolescent global disordered eating, shape, and weight concern (p-values <0.05); adolescent autonomy related to less weight concern (p = 0.03). Better parent communication skills were associated with less adolescent eating concern (p = 0.04), and observed dyadic mutuality related to adolescents' lower insulin resistance (p = 0.03). Parent-adolescent interaction qualities during food/eating-related disagreements show associations with parent-reported food practices and adolescent disordered eating. This method may offer a tool for measuring the qualities of parent-adolescent food/eating-related interactions. A nuanced understanding of conversations about food/eating may inform family-based intervention in youth at-risk for adult obesity.

Mental health and health behaviors among college student mentors in a randomized controlled trial interrupted by COVID-19.

Objective: The benefits of mindfulness-training and mentoring for college students have yet to be investigated. We aimed to provide an exploratory and descriptive account of their potential benefits during the COVID-19 pandemic. Participants: In February 2020, 49 undergraduates (M = 20.51 years-old; 94% female) participated in a randomized trial of 12-week mentoring + mindfulness or mentoring-as-usual. After five weekly mentoring-sessions, programs were interrupted by COVID-19; mentoring continued online. Methods: Undergraduates completed questionnaires about mental health, behaviors, and regulatory processes in February and July 2020, with additional COVID-19-related questions at follow-up. Results: Participants reported moderate COVID-19-related perceived stress, but mental health, health behaviors, and regulatory processes did not diminish over time, with no condition differences. Undergraduates described using contemplative practices and social support to cope with COVID-19-stress. Conclusions: Undergraduates showed stable mental health/health behaviors despite moderate COVID-19-related-stress. Future research on mentoring with a mindfulness component among a larger and more heterogeneous sample will be necessary.

Inadequate sleep moderates effects of interparental conflict appraisals on adolescent adjustment.

OBJECTIVES: Previous research and theory suggest that interparental conflict that is perceived by youth as frequent/intense, threatening, and/or the responsibility of the youth is predictive of adjustment problems. In contrast, sleep, an important precursor to emotion regulation, is likely a protective factor for youth experiencing interparental conflict. The goal of the current study was to investigate the extent to which adolescents who maintain better and/or longer sleep are buffered from the adjustment problems associated with greater interparental conflict. METHODS: One-hundred and fifty adolescents completed questionnaires assessing interparental conflict (frequency/intensity perceptions as well as threat and self-blame appraisals) as well as internalizing and externalizing behaviors. Participants also wore an actigraph over 1 week to objectively measure sleep quantity and quality; 123 participants had valid actigraphy data. RESULTS: Results of structural equation modeling analyses revealed that greater sleep quality weakened the association between interparental conflict and adjustment problems, particularly internalizing behaviors. However, sleep quantity was not a moderator. CONCLUSION: These results suggest that higher quality sleep may protect adolescents from the negative effects of interparental conflict.

Facilitators and barriers for parental consent to pediatric emergency research.

BACKGROUND: Obtaining informed consent for clinical research in the pediatric emergency department (ED) is challenging. Our objective was to understand the factors that influence parental consent for ED studies. METHODS: This was a cross-sectional survey assessing parents' willingness to enroll their children into an ED research study. Parents reporting a willingness to enroll in ED studies were presented with two hypothetical scenarios, a low-risk and a high-risk study, and then asked about decision influencers affecting consent. Parents expressing a lack of willingness to enroll were asked which decision influencers impacted their consent decision. RESULTS: Among 118 parents, 90 (76%) stated they would be willing to enroll their child into an ED study; of these, 86 (96%) would consent for a low-risk study and 54 (60%) would consent for a high-risk study. Caucasian parents, and those with previous research exposure, were more likely to report willingness to participate. Those who would consent to the high-risk study cited "benefits that research would provide to future children" most strongly influenced their decision to agree. CONCLUSIONS: ED investigators should highlight the benefits for future children and inquire about parents' previous exposure to research to enhance ED research enrollment. Barriers to consent in non-Caucasian families should be further investigated. IMPACT: Obtaining consent for pediatric emergency research is challenging and this study identified factors influencing parental consent for research in EDs. Benefits for future children and parents' previous research experience were two of the most influential factors in parents' willingness to consent to ED research studies. These findings will help to improve enrollment in ED research studies and better our understanding of how to promote the health and well-being of pediatric patients.

Within-Person variations in mindfulness mediate effects of daily stressors on psychological distress in adolescence.

OBJECTIVE: We tested two competing models linking daily stress, mindfulness, and psychological distress in adolescence: 1) whether daily mindfulness moderates the impact of daily stressors on psychological distress or 2) whether mindfulness mediates the relationship between greater daily stressors and psychological distress. METHODS: Every evening for a week, 138 adolescents completed ecological momentary assessments (EMAs). Daily diaries assessed negative events, work-school conflict, mindfulness, and perceived stress. Multilevel mediation and moderation were tested. RESULTS: Results indicated that there were meaningful variations in adolescent mindfulness from day-to-day, and supported mediation rather than moderation; the within-person association between stressors and psychological distress was mediated by mindfulness at the daily level. CONCLUSION: It may be too challenging for adolescents to remain in a mindful state during stress to effectively use mindfulness as a buffer. Instead, daily stressors may indirectly impact psychological distress through decreasing mindfulness.

Health effects of COVID-19 for vulnerable adolescents in a randomized controlled trial.

Emerging evidence suggests the coronavirus disease 2019 (COVID-19) pandemic is adversely affecting adolescents' mental health and health behaviors, particularly among those with preexisting mental health conditions and from lower socioeconomic backgrounds. However, direct tests of changes in health outcomes among vulnerable adolescents from before to during COVID-19 are limited. In addition, little is known about how to buffer adolescents, particularly those who are most vulnerable, against stress-related decrements in health. This randomized controlled trial begins to fill these gaps in the literature by exploring changes in mental health, health behaviors, executive function, emotion regulation, and mindfulness among vulnerable adolescents involved in a mentoring program during the COVID-19 pandemic. It also examined to what extent there were protective benefits of incorporating mindfulness training within a mentoring program for buffering adolescents from negative pandemic health effects. Thirty-five adolescents (Mage = 12.9, 37% female) and 32 parents (Mage = 44.75, 80% female) completed questionnaires at baseline (February 2020) and follow-up (July 2020). There were few significant reductions in health; instead, on average, youth reported improvements in sleep, emotion regulation, executive function, and mindfulness over time. Adolescents randomized to mentoring + mindfulness displayed significantly less posttraumatic stress disorder (PTSD) symptomatology and emotional impulsivity at follow-up, compared to the mentoring-as-usual condition. These pilot findings suggest that mentoring with a mindfulness training component may offer an effective strategy for protecting adolescents from deteriorations in health outcomes during COVID-19. Further, there may be unique benefits of mindfulness training for vulnerable youth as a way to adapt to stressful events. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Dispositional Mindfulness is Cross-Sectionally Predicted by Interactions between Interparental Conflict and Parent-Child Relationships.

Theory emphasizes the importance of the family environment for the development of dispositional mindfulness, but past research has focused exclusively on parent-child attachment relationships as family-level predictors of mindfulness. Our goal was to examine unique and joint associations of both interparental conflict and parent-child relationship quality with dispositional mindfulness. Participants were 150 youth (14-21 yrs) who reported the warmth and support in their relationships with mothers and fathers separately, as well as their appraisals of the properties of their parents' conflict, how threatening that conflict is, and how responsible for it they feel, in addition to dispositional mindfulness. Results indicated consistent interactions between conflict properties and mother-child relationship quality in relation to dispositional mindfulness. Dispositional mindfulness was lowest for youth who reported low levels of frequent/intense interparental conflict and poor-quality relationships with mothers. In contrast, either self-blame/threat or poor-quality relationships with mothers predicted lower levels of dispositional mindfulness. Implications for theory and practice are discussed.

Associations of adverse childhood experiences with stress physiology and insulin resistance in adolescents at risk for adult obesity.

Adverse childhood experiences (ACEs) heighten the risk for adult obesity and cardiometabolic disease, but physiological factors underlying this connection are not well understood. We determined if ACEs were associated with physiological stress response and insulin resistance in adolescents at risk for adult obesity. Participants were 90 adolescents 12.0-17.5 years (50% female, 30% Hispanic/Latinx), at risk for adult obesity by virtue of above-average body mass index (BMI; kg/m2 ≥ 70th percentile) or parental obesity (BMI ≥ 30 kg/m2 ). ACEs were determined as presence (vs. absence) based upon the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Physiological stress response was measured as heart rate/blood pressure response to the Trier Social Stress Test. Homeostatic model assessment of insulin resistance was determined from fasting glucose/insulin. Sixty-one percent of adolescents reported positive ACE history. The presence of ACEs predicted greater heart rate (p < .001) and diastolic blood pressure (p = .02) response to stress, controlling for age, sex, race/ethnicity, puberty, and BMI standard score. Systolic blood pressure and insulin resistance did not differ by ACE history (p-values > .08). Findings suggest heightened sympathetic stress response in adolescence could be explanatory in how ACEs increase the risk for later cardiometabolic disease. Future studies should characterize ACEs in relationship to day-to-day variations in adolescents' stress physiology and glucose homeostasis.

The role of mindfulness in associations among depression symptoms, sleep duration, and insulin resistance in adolescents.

Sleep difficulties may be one explanatory factor in the association between depression and insulin resistance; yet, explicit tests of this hypothesis are lacking. We determined if there was an indirect effect of depression symptoms on insulin resistance through sleep duration in adolescents at risk for excess weight gain. We also investigated whether dispositional mindfulness moderated the interconnections among depression, sleep, and insulin resistance. Ninety adolescents (14.2 ± 1.6y; 50% female) at risk for excess weight gain (body mass index [BMI, kg/m2] z score 1.6 ± 0.6) participated in the cross-sectional, baseline phase of a health behaviors study. Depression was assessed with the Center for Epidemiologic Studies-Depression Scale, sleep duration with the Sleep Habits Survey, and mindfulness with the Mindful Attention and Awareness Scale. Homeostatic model assessment of insulin resistance was determined from fasting insulin and glucose. The product-of-coefficients method was used to test the indirect effect of depression on insulin resistance through sleep duration, accounting for age, sex, BMIz, puberty, and socioeconomic status (SES). Dispositional mindfulness was tested as a moderator of the associations among depression, sleep, and insulin resistance. There was a significant indirect effect of depression on insulin resistance through sleep duration, controlling for age, sex, BMIz, puberty, and SES, 95%CI [0.001, 0.05]. Dispositional mindfulness moderated the association between sleep duration and insulin resistance, such that lower sleep duration related to greater insulin resistance only among adolescents with lower mindfulness (p < .001). Short sleep may be one explanatory factor in the depression-insulin resistance connection in adolescents at risk for excess weight gain. Adolescents with poorer mindfulness and short sleep are at highest risk for insulin resistance, whereas higher mindfulness may be protective.

Does dispositional mindfulness buffer the links of stressful life experiences with adolescent adjustment and sleep?

According to the mindfulness stress buffering hypothesis, mindfulness protects individuals from negative effects of stress. Prior investigations focused on the potential of mindfulness for reducing internalizing symptoms for adults in the context of general stress. We provided the first test of the mindfulness stress buffering hypothesis in the context of both adolescent general stress and interparental conflict (IPC) in relation to internalizing and externalizing, as well as sleep. Participants were 150 adolescents who reported dispositional mindfulness, perceived stress, IPC, internalizing, and externalizing. Participants wore an actigraph which objectively measured sleep for a week. Results suggested a stress buffering effect of mindfulness for the effects of general stress on internalizing symptoms at trend levels. Mindfulness stress buffering was not evident in relation to externalizing or sleep, or for the effect of IPC appraisals on adjustment or sleep. Greater IPC appraisals were associated with greater sleep onset latency, but mindfulness was not associated with objective measures of sleep quality or quantity. This study indicates that mindfulness may protect adolescents from the internalizing problems that often result from general stress, but that these stress buffering effects of mindfulness may not generalize to all types of stressors or adjustment/health outcomes.

Effects of a mindfulness-induction on subjective and physiological stress response in adolescents at-risk for adult obesity.

BACKGROUND: Mindfulness-training may benefit stress response and stress-eating, yet few studies have experimentally tested these effects in adolescents. In this short communication, we report whether a brief mindfulness-induction affected acute stress response and stress-eating in adolescents at-risk for adult obesity. We explored disordered eating as a moderator. METHOD: Twenty-nine adolescents (age 14 ± 2 y) at-risk for adult obesity participated in a within-subjects, randomized crossover experiment. Following a 10-minute mindfulness or neutral-induction on different days in random order, the Trier Social Stress Test adapted for adolescents was administered, followed by an ad libitum lunch meal. Physiological stress response (heart rate, blood pressure) and subjective stress response (anxiety, mindlessness) were determined with area under the curve with respect to increase. Stress-eating was measured as test meal energy consumed. Global disordered-eating and binge-eating were assessed with the Eating Disorders Examination-Questionnaire. RESULTS: Relative to a neutral-induction, a mindfulness-induction reduced state anxiety response (p = .04). There were significant interactions of induction-type by global disordered-eating (p = .02) and binge-eating (p = .03), such that the mindfulness-induction most reduced anxiety response in adolescents with relatively lower global disordered-eating and those with no binge-eating. Induction-type also interacted with binge-eating in predicting diastolic blood pressure (p = .03). A mindfulness-induction, versus neutral-induction, most reduced diastolic blood pressure response in adolescents with binge-eating. CONCLUSIONS: Brief mindfulness-training may alter some aspects of acute stress response, with variations by disordered-eating. Future research should test alternative mindfulness induction-types (e.g., acceptance/self-compassion) to improve our understanding of how mindfulness-training may benefit adolescents at-risk for adult obesity.

Dispositional mindfulness predicts cortisol, cardiovascular, and psychological stress responses in adolescence.

BACKGROUND: Past studies investigating the link between mindfulness and stress responding (i.e., emotional, psychological, and physiological responses to perceived threat or challenge) have focused on mindfulness training and on adult populations. In addition, research has not directly examined whether high mindfulness is particularly beneficial under conditions of high stress. To fill these gaps, the current study examined whether dispositional mindfulness predicts reduced cortisol, psychological, and cardiovascular stress responding in adolescence, and whether these effects are moderated by perceived life stress. METHODS: Adolescents (N = 150; 14-21yrs) completed measures of dispositional mindfulness, perceived life stress, emotional reactivity, and appraisals of the Trier Social Stress Test (TSST). Cortisol and blood pressure responses were measured. RESULTS: Higher dispositional mindfulness predicted reduced emotional and cardiovascular responding to the TSST, as well as less-negative task appraisals. In contrast, higher dispositional mindfulness predicted greater cortisol reactivity (or increases in cortisol in response to the TSST), particularly for adolescents experiencing lower perceived life stress. CONCLUSION: These findings add to the body of literature indicating that greater mindfulness predicts improved stress responding, but do not suggest that mindfulness buffers the effects of high stress on adolescent stress responding.

Pre-filled syringes: a review of the history, manufacturing and challenges.

Pre-filled syringes are convenient devices for the delivery of parenteral medications. They are small which makes them easy to carry and are dependable for delivering a precise dose of medication. These and many other reasons are leading to their growth in the pharmaceutical market. There are a number of review articles that describe the advantages and disadvantages of pre-filled syringes. However, there are few journal articles that present information on their manufacturing and challenges. The intent of this review article is to provide information on the history of the pre-filled syringe, methods of their manufacture, methods of filling syringes as a drug product and to examine the types of syringes available. This type of knowledge can familiarize the formulation scientist with the choices available and their possible challenges.

Mechanism of 2-hydropropyl-beta-cyclodextrin in the stabilization of frozen formulations.

Freezing of commonly used parenteral products to increase pharmaceutical stability for cost-saving purposes is a common practice in patient care. However, frozen meropenem, a model drug, in saline has a shelf life of less than a month due to the low glass transition temperature (Tg'): below -40°C. When meropenem is formulated with the 2-hydroxypropyl-ß-cyclodextrin (HPBC) the shelf life (⩾90% potency) is extrapolated to be greater than one year at -25°C based on data for storage at 6months. The mechanisms that may explain meropenem-HPBC formulation frozen stability include vitrification and/or formation of an inclusion complex. Although NMR data indicated complexation of meropenem by HPBC in a ratio of 0.6:1, inclusion was unlikely to be the mechanism as stability was not extended to the thawed solutions. Therefore, vitrification is concluded to be the stabilization mechanism. The Tg' for meropenem-HPBC (13.3%) formulation at pH 7.9 was -17.75°C which was similar to that of a meropenem solution formulated with a known vitrifying agent, Dextran 40. This higher Tg' for HPBC was unexpected based on trends predicted by the Fox-Flory equation. Trial formulations containing either Dextran 1, Dextran 40, hydroxyethyl starch, or sulfobutyl-beta-cyclodextrin heptasodium (Captisol®) were also unable to stabilize meropenem as the Tg' values were below the frozen storage temperature. Upon 6-month storage, potency losses were -3.0% and -7.7% for meropenem frozen premix formulated in 13.3% HPBC (pH 7.9) at -25 and -20°C storage, respectively; versus -31.2% and -60.8% for controls. Frozen premixes with high ionic strength (containing NaCl or Captisol®) and/or at pH 7.3 were also found to be unstable.

Case study: contamination of heparin with oversulfated chondroitin sulfate.

In late 2007 and early 2008, a cluster of adverse events in patients receiving Heparin Sodium Injection occurred in the United States and in some countries in Europe. The adverse events were reported as being "allergic type" reactions, chiefly characterized by acute hypotension, nausea, and shortness of breath. The root cause of the cluster of adverse events was determined to be a contamination of the heparin by oversulfated chondroitin sulfate. The isolation and structure determination of this contaminant was accomplished by an FDA-led consortium of academic and government laboratories and independently by Baxter Healthcare, whose vial products were first identified in the USA as being associated with the adverse events. Oversulfated chondroitin sulfate was shown to produce acute hypotension in animal models, demonstrating that it was most likely the causative agent responsible for certain of the reported adverse events in patients receiving the contaminated heparin products.

NMR of heparin API: investigation of unidentified signals in the USP-specified range of 2.12-3.00 ppm.

This article addresses the identification and quantification of the chemical species resulting in resonances at 2.17 and 2.25 ppm in the (1)H nuclear magnetic resonance (NMR) spectrum of pharmaceutical-grade heparin sodium. The NMR signals in question were first confirmed to arise from chemical moieties covalently attached to the heparin molecule through NMR diffusion experiments as well as chemical treatment of heparin active pharmaceutical ingredient (API) containing the resonances. The material responsible for the extra NMR signals was then demonstrated by NMR spiking studies to be something other than oversulfated chondroitin sulfate and was finally identified as an O-acetylation product of heparin through (13)C labeling experiments with subsequent NMR analysis. The extent of O-acetylation was quantified using three orthogonal techniques: (1)H NMR, ion chromatography, and headspace gas chromatography/mass spectrometry. The results of this work showed good agreement between the three quantitative methods developed to analyze the signals in the United States Pharmacopeia-specified region of 2.12-3.00 ppm for heparin API.

Nanoformulated antiretroviral drug combinations extend drug release and antiretroviral responses in HIV-1-infected macrophages: implications for neuroAIDS therapeutics.

We posit that improvements in pharmacokinetics and biodistributions of antiretroviral therapies (ART) for human immunodeficiency virus type one-infected people can be achieved through nanoformulationed drug delivery systems. To this end, we manufactured nanoparticles of atazanavir, efavirenz, and ritonavir (termed nanoART) and treated human monocyte-derived macrophages (MDM) in combination therapies to assess antiretroviral responses. This resulted in improved drug uptake, release, and antiretroviral efficacy over monotherapy. MDM rapidly, within minutes, ingested nanoART combinations, at equal or similar rates, as individual formulations. Combination nanoART ingested by MDM facilitated individual drug release from 15 to >20 days. These findings are noteworthy as a nanoART cell-mediated drug delivery provides a means to deliver therapeutics to viral sanctuaries, such as the central nervous system during progressive human immunodeficiency virus type one infection. The work brings us yet another step closer to realizing the utility of nanoART for virus-infected people.

NanoART synthesis, characterization, uptake, release and toxicology for human monocyte-macrophage drug delivery.

BACKGROUND: Factors limiting the efficacy of conventional antiretroviral therapy for HIV-1 infection include treatment adherence, pharmacokinetics and penetration into viral sanctuaries. These affect the rate of viral mutation and drug resistance. In attempts to bypass such limitations, nanoparticles containing ritonavir, indinavir and efavirenz (described as nanoART) were manufactured to assess macrophage-based drug delivery. METHODS: NanoART were made by high-pressure homogenization of crystalline drug with various surfactants. Size, charge and shape of the nanoparticles were assessed. Monocyte-derived macrophage nanoART uptake, drug release, migration and cytotoxicity were determined. Drug levels were measured by reverse-phase high-performance liquid chromatography. RESULTS: Efficient monocyte-derived macrophage cytoplasmic vesicle uptake in less than 30 min based on size, charge and coating was observed. Antiretroviral drugs were released over 14 days and showed dose-dependent reduction in progeny virion production and HIV-1 p24 antigen. Cytotoxicities resulting from nanoART carriage were limited. CONCLUSION: These results support the continued development of macrophage-mediated nanoART carriage for HIV-1 disease.