Fused deposition modeling three-dimensional printing of flexible polyurethane intravaginal rings with controlled tunable release profiles for multiple active drugs.

We designed and engineered novel intravaginal ring (IVR) medical devices via fused deposition modeling (FDM) three-dimensional (3D) printing for controlled delivery of hydroxychloroquine, IgG, gp120 fragment (encompassing the CD4 binding site), and coumarin 6 PLGA-PEG nanoparticles (C6NP). The hydrophilic polyurethanes were utilized to 3D-print reservoir-type IVRs containing a tunable release controlling membrane (RCM) with varying thickness and adaptable micro porous structures (by altering the printing patterns and interior fill densities) for controlled sustained drug delivery over 14 days. FDM 3D printing of IVRs were optimized and implemented using a lab-developed Cartesian 3D printer. The structures were investigated by scanning electron microscopy (SEM) imaging and in vitro release was performed using 5 mL of daily-replenished vaginal fluid simulant (pH 4.2). The release kinetics of the IVR segments were tunable with various RCM (outer diameter to inner diameter ratio ranging from 1.12 to 2.61) produced from FDM 3D printing by controlling the printing perimeter to provide daily zero-order release of HCQ ranging from 23.54 ± 3.54 to 261.09 ± 32.49 µg/mL/day. IgG, gp120 fragment, and C6NP release rates demonstrated pattern and in-fill density-dependent characteristics. The current study demonstrated the utility of FDM 3D printing to rapidly fabricate complex micro-structures for tunable and sustained delivery of a variety of compounds including HCQ, IgG, gp120 fragment, and C6NP from IVRs in a controlled manner.

The Reynolds Adolescent Depression Scale in New Zealand adolescents.

OBJECTIVE: To examine aspects of the reliability and validity of the Reynolds Adolescent Depression Scale (RADS) in measuring depression in New Zealand adolescents of all major ethnic groups. METHOD: A sample of 9699 randomly selected New Zealand secondary school students participated in the Youth2000 Health and Wellbeing Survey which included the RADS. Data from this survey have been used to assess some aspects of the reliability and validity of the RADS in the New Zealand context across different ethnic groups. Cronbach's alpha, item-total score correlations, correlation to other questions and a factor analysis were done in order to examine the internal reliability, content validity, convergent validity and construct validity of the data and compare to the original Reynolds validation study. RESULTS: Tests of the scale resulted in scores over 0.90 on Cronbach's alpha and high item-total score correlations, with a median correlation of 0.62 and 25 of the 30 correlations measuring more than 0.5. The scores were found to have similar factor structure to the original scale and the correlations to other depression related questions indicate acceptable concurrent validity. CONCLUSIONS: On all of the tests conducted, the RADS was found to have acceptable reliability and validity for New Zealand adolescents across the major different ethnic groups, indicating that it is a valid and appropriate instrument to use with New Zealand adolescents.