A unified thermodynamic and kinetic approach for prediction of microcapsule morphologies.

HYPOTHESIS: Microcapsule formation, following internal phase separation by solvent evaporation, is controlled by two main factors of thermodynamic and kinetic origin. Morphology prediction has previously focused on the final thermodynamical state in terms of spreading conditions, limiting the prediction accuracy. By additionally considering kinetic effects as the emulsion droplet evolves through the two-phase region of its ternary phase diagram during solvent evaporation, this should enhance prediction accuracy and explain a wider range of morphologies. EXPERIMENTS: Dynamical interfacial tensions, and thereby spreading coefficients, during the formation of poly(methyl methacrylate) and poly(d,l-lactic-co-glycolic acid) microcapsules were measured by first establishing the boundaries and tie-lines of the ternary system in the emulsion droplets. Kinetic effects during the formation were investigated by varying the solvent evaporation rate and hence the time for polymer shell formation equilibration. The theory was validated by comparing predicted morphologies to microscopic snapshots of intermediate and final morphologies. FINDINGS: The proposed theory explained both intermediate acorn and core-shell morphologies, where a late transition from acorn to core-shell produced microcapsules containing highly off-centered cores. By considering the kinetic factors, the formulation could be altered from yielding kinetically frozen acorns to core-shell and from yielding multicore to single core microcapsules.

Polyanhydride Microcapsules Exhibiting a Sharp pH Transition at Physiological Conditions for Instantaneous Triggered Release.

Stimulus-responsive microcapsules pose an opportunity to achieve controlled release of the entire load instantaneously upon exposure to an external stimulus. Core-shell microcapsules based on the polyanhydride poly(bis(2-carboxyphenyl)adipate) as a shell were formulated in this work to encapsulate the model active substance pyrene and enable a pH-controlled triggered release. A remarkably narrow triggering pH interval was found where a change in pH from 6.4 to 6.9 allowed for release of the entire core content within seconds. The degradation kinetics of the shell were measured by both spectrophotometric detection of degradation products and mass changes by quartz crystal microbalance with dissipation monitoring and were found to correlate excellently with diffusion coefficients fitted to release measurements at varying pH values. The microcapsules presented in this work allow for an almost instantaneous triggered release even under mild conditions, thanks to the designed core-shell morphology.

A feasibility trial of online Acceptance and Commitment Therapy for women with provoked vestibulodynia.

OBJECTIVES: Acceptance and Commitment Therapy (ACT) is an established treatment for chronic pain. However, it is a form of treatment that have not yet been applied much in the treatment of persistent vulvar pain disorders. This study examines the feasibility and preliminary effects of online ACT for patients with provoked vestibulodynia. METHODS: Women diagnosed with provoked vestibulodynia were assigned randomly either to online ACT or to a waitlist control group. Feasibility was assessed in terms of recruitment potential, treatment credibility, completions rates, retention in trial, and data quality. Participants completed measures of pain with sexual activity, sexual functioning, emotional and relational adjustment, and potential treatment processes before and after treatment. RESULTS: Of the 111 women who were invited to participate in the study, 44 were included (39.6 % recruitment rate). Thirty seven participants (84.1 %) completed the pre-treatment assessment. Participants who received online ACT rated treatment credibility positively, and completed on average 4.31 (SD=1.60) of the six treatment modules. Of participants, 34 provided post treatment data, giving a trial retention rate of 77 %. Effects of online ACT, as compared to waitlist, were large for pain acceptance and quality of life, medium for anxiety and pain catastrophizing, and small for sexual satisfaction, pain with sexual activity, and relationship adjustment. CONCLUSIONS: With some adjustments to recruitment procedures, a full scale randomized controlled trial of online ACT for provoked vestibulodynia appears feasible.

Long-term effect of stepped-care vs in-person cognitive behavioral therapy for pediatric obsessive-compulsive disorder.

Long-term follow-up data from trials of digital mental health interventions are rare. This study reports 2-year follow-up data from a non-inferiority trial (N = 152) comparing stepped-care (internet-delivered cognitive behavioral therapy [CBT] followed by traditional in-person CBT if needed) vs in-person CBT for pediatric obsessive-compulsive disorder. Both treatment groups had comparable long-term effects, with the majority of participants being responders (stepped-care 66 %; in-person CBT 71 %) 2 years after the end of treatment.

Microcapsule functionalization enables rate-determining release from cellulose nonwovens for long-term performance.

Functional textiles is a rapidly growing product segment in which sustained release of actives often plays a key role. Failure to sustain the release results in costs due to premature loss of functionality and resource inefficiency. Conventional application methods such as impregnation lead to an excessive and uncontrolled release, which - for biocidal actives - results in environmental pollution. In this study, microcapsules are presented as a means of extending the release from textile materials. The hydrophobic model substance pyrene is encapsulated in poly(D,L-lactide-co-glycolide) microcapsules which subsequently are loaded into cellulose nonwovens using a solution blowing technique. The release of encapsulated pyrene is compared to that of two conventional functionalization methods: surface and bulk impregnation. The apparent diffusion coefficient is 100 times lower for encapsulated pyrene compared to impregnated pyrene. This clearly demonstrates the rate-limiting barrier properties added by the microcapsules, extending the potential functionality from hours to weeks.

Effect of an Internet-Delivered Stepped-Care Program vs In-Person Cognitive Behavioral Therapy on Obsessive-Compulsive Disorder Symptoms in Children and Adolescents: A Randomized Clinical Trial.

Importance: In most countries, young people with obsessive-compulsive disorder have limited access to specialist cognitive behavioral therapy (CBT), a first-line treatment. Objective: To investigate whether internet-delivered CBT implemented in a stepped-care model is noninferior to in-person CBT for pediatric obsessive-compulsive disorder. Design, Setting and Participants: A randomized clinical noninferiority trial conducted at 2 specialist child and adolescent mental health clinics in Sweden. Participants included 152 individuals aged 8 to 17 years with obsessive-compulsive disorder. Enrollment began in October 2017 and ended in May 2019. Follow-up ended in April 2020. Interventions: Participants randomized to the stepped-care group (n = 74) received internet-delivered CBT for 16 weeks. Nonresponders at the 3-month follow-up were then offered a course of traditional face-to-face treatment. Participants randomized to the control group (n = 78) immediately received in-person CBT for 16 weeks. Nonresponders at the 3-month follow-up received additional face-to-face treatment. Main Outcomes and Measures: The primary outcome was the masked assessor-rated Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score at the 6-month follow-up. The scale includes 10 items rated from 0 (no symptoms) to 4 (extreme symptoms), yielding a total score range of 0 to 40, with higher scores indicating greater severity. Assessors were masked to treatment allocation at pretreatment, posttreatment, 3-month follow-up, and 6-month follow-up assessments. The predefined noninferiority margin was 4 points on the CY-BOCS. Results: Among the 152 randomized participants (mean age, 13.4 years; 94 [62%] females), 151 (99%) completed the trial. At the 3-month follow-up, 34 participants (46%) in the stepped-care group and 23 (30%) in the in-person CBT group were nonresponders. At the 6-month follow-up, the CY-BOCS score was 11.57 points in the stepped-care group vs 10.57 points in the face-to-face treatment group, corresponding to an estimated mean difference of 0.91 points ([1-sided 97.5% CI, -∞ to 3.28]; P for noninferiority = .02). Increased anxiety (30%-36%) and depressive symptoms (20%-28%) were the most frequently reported adverse events in both groups. There were 2 unrelated serious adverse events (1 in each group). Conclusions and Relevance: Among children and adolescents with obsessive-compulsive disorder, treatment with an internet-delivered CBT program followed by in-person CBT if necessary compared with in-person CBT alone resulted in a noninferior difference in symptoms at the 6-month follow-up. Further research is needed to understand the durability and generalizability of these findings. Trial Registration: ClinicalTrials.gov Identifier: NCT03263546.

Formulation of polyphthalaldehyde microcapsules for immediate UV-light triggered release.

Triggered release from responsive drug reservoirs activated by remote stimuli is desired in a range of fields. Critical bottlenecks are cost-efficient formulation avenues applicable for industrial scale-up, viable triggers and immediate release rather than continuous release upon activation. UV-sensitive microcapsules based on self-immolating polymers in combination with thin shells and morphological weak spots should allow for immediate triggered release. Polyphthalaldehyde-based microcapsules were prepared using several variations of the internal phase separation route. In addition, a fluorescence microscopy method was developed to study both the microcapsule morphology and the triggered release in-situ. The microcapsule formation was driven by the surface activity of the stabilizer, effectively lowering the high polymer-water interfacial tension, which is in sharp contrast to conventional encapsulation systems. Contrary to previous findings, a core-shell morphology was obtained via slow emulsion-to-suspension transformation. Rapid transformation captured intermediate inverted core-shell structures. The capsules were highly sensitive to both acid- and UV-mediated triggers, leading to an unzipping and rupturing of the shell that released the core content. Poly(methacrylic acid)-stabilized microcapsules displayed immediate UV-triggered release provided by their stimuli-sensitive blueberry morphology. Both capsules in aqueous and dry environment started to lose their core content after less than one minute of UV light exposure.