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

Abstract

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. Graphical abstract

Biodegradable and pH-Responsive Amphiphilic Poly(succinimide) Derivatives for Triggered Release of Antibiotics for Management of Infected Wounds

“…The turbidity was calculated according to the reference. 32 Acid−base titration was conducted for the AUA-PSI samples. AUA-PSI solutions were diluted to 1.0 mg/mL with DI water, and 10 mL of each sample was used for the titration.…”

“…The pH of the solution was adjusted with 0.1 N HCl and 0.1 N NaOH solutions. The turbidity was calculated according to the reference …”

Personalization of Complex Vaginal Inserts of Ethylene Vinyl Acetate via 3D‐Printing

“…[37,51] Only a single study addressed this topic, more specifically the effect of infill pattern on the release of non-biodegradable TPU-based reservoirtype IVRs. [52] The IVRs were printed with infill densities below 100% (i.e. a pore network was created) and additionally, the perimeter did not fully cover the IVR.…”

3D printing of a controlled urea delivery device for the prevention of tooth decay

“…The combination of 3D scanning with 3D printing technologies allows the rapid manufacturing of personalized pharmaceutical devices with high complexity and precision (Paunović et al, 2021), (Khaled et al, 2015), (Chen et al, 2022). Among additive manufacturing technologies, fused deposition modeling (FDM) is a widely used technique based on a layer-by-layer material deposition.…”

“…These composite filaments are further used for the 3D printing of controlled-release delivery devices, such as drug-eluting dental trays (Liang et al, 2018), (Berger et al, 2022). The latter can be designed on demand to match patients' anatomy and meet individual requirements (Chen et al, 2022), (Liang et al, 2018).…”