“From Academia” features recent, relevant, close to commercialization academic publications. Subjects include but not limited to healthcare 3D printing, 3D bioprinting, and related emerging technologies. In this issue, we will share three recent publications focusing on how to leverage 3D printing to improve drug delivery. The first article described a bilayer FDM 3D printed tablet that can release TB medication at two different PH, thereby potentially optimize drug potency and avoid drug interactions. The second publication describes a dual extrusion 3D printing process that can leverage different material compositions and geometries to create different drug release profiles. In the final article, researchers described a multifunctional bone graft as a drug delivery vehicle by incorporating the three primary soy isoflavones: genistein, daidzein, and glycitein onto a 3D printed (3DP) tricalcium phosphate (TCP) scaffold with designed pores, endowing them with in vitro chemopreventive, bone-cell proliferating, and immune-modulatory potential.
Email: Rance Tino (tino.rance@gmail.com) if you want to share relevant academic publications with us.
3D printed bilayer tablet with dual controlled drug release for tuberculosis treatment
Authored by Atabak Ghanizadeh Tabriz, Uttom Nandi, Andrew P. Hurt, Ho-Wah Hui, Shyam Karki, Yuchuan Gong, Sumit Kumar, Dennis Douroumis. International Journal of Pharmaceutics. January 2020
Abstract:
In this study Fusion Deposition Modelling (FDM) was employed to design and fabricate a bilayer tablet consisting of isoniazid (INZ) and rifampicin (RFC) for the treatment of tuberculosis.
INZ was formulated in hydroxypropyl cellulose (HPC) matrix to allow drug release in the stomach (acidic conditions) and RFC was formulated in hypromellose acetate succinate (HPMC – AS) matrix to allow drug release in the upper intestine (alkaline conditions). This design may offer a better clinical efficacy by minimizing the degradation of RFC in acidic conditions and potentially avoid drug-drug interaction.
The bilayer tablet was prepared by fabricating drug-containing filaments using hot-melt extrusion (HME) coupled with 3D printing. The HME and 3D printing processes were optimized to avoid drug degradation and assure consistent deposition of drug-containing layers in the tablet.
The in-vitro drug release rate was optimized by varying drug loading, infilling density, and covering layers. Greater than 80% of INZ was released in 45 mins at pH 1.2 and approximately 76% of RFC was releases in 45 mins after the dissolution medium was changed to pH 7.4. The work illustrated the potential application of FDM technology in the development of oral fixed-dose combinations for personalized clinical treatment.
Speed it up, slow it down: An issue of bicalutamide release from 3D printed tablets
Authored by Witold Jamroz, Mateusz Kurek, Joanna Szafraniec-Szczesny, Anna Czech, Karolina Gawlak, Justyna Knapik-Kowalczuk, Bartosz Leszczynski, Andrzej Wrobel, Marian Paluch, Renata Jachowicz. Euoprean Journal of Pharmaceutrical Science. February 2020
Abstract:
The article describes the preparation and characterization of 3D-printed tablets with bicalutamide obtained using two-material co-extrusion-based fused deposition modeling (FDM).
This method is a modification of typical two-material FDM where separate nozzles are used to print from two filaments. In this work, we used a ZMorph® 3D printer with DualPro printhead which allows us to co-extruded two filaments through a single nozzle. This approach gives the opportunity to modify tablet properties in a wide range, especially the dissolution rate, by producing dosage forms with a complex design.
The great advantage of this method is that switching between immediate dosage form and controlled release does not require any change in the 3D-printer set-up. We checked the accuracy of co-extrusion printing simply by weighing the amounts of soluble and insoluble material in the printed object as well as calculating the volumes of the printed objects from micro-computed tomography (µ-CT) images.
We printed several tablets with different designs including simple one-material tablets, two- and three-compartment tablets with various internal structures and compositions of the printing path. The dissolution tests were conducted in sink and non-sink conditions. We obtained tablets with desired bicalutamide dissolution profiles, i.e. immediate, controlled, and combined.
The formation of spatial matrix slows down the dissolution in controlled and combined release bicalutamide tablets what was confirmed by µ-CT analysis before and after dissolution.
Controlled release of soy isoflavones from multifunctional 3D printed bone tissue engineering scaffolds
Authored by Naboneeta Sarkar, Susmita Bose. Acta Biomaterialia. September 2020
Abstract:
Recent challenges in post-surgical bone tumor management have elucidated the need for a multifunctional scaffold, which can be used for residual tumor-cell suppression, defect repair, and simultaneous bone regeneration.
In this perspective, 3D printing allows to create a wide variety of patient-specific implant with complex porous architecture and compatible mechanical strength to that of cancellous bone.
Here, a multifunctional bone graft substitute is designed by incorporating the three primary soy isoflavones: genistein, daidzein, and glycitein onto a 3D printed (3DP) tricalcium phosphate (TCP) scaffold with designed pores, endowing them with in vitro chemopreventive, bone-cell proliferating, and immune-modulatory potential.
The interconnected porosity and biodegradability of 3DP TCP ceramics have allowed controlled release kinetics of genistein, daidzein, and glycitein in acidic and physiological buffer medium for 16 days, which is fitted with Korsmeyer-Peppas model.
The presence of genistein, a well-known natural biomolecule shows a 90% reduction in vitro osteosarcoma (MG-63) cell viability and proliferation after 11 days. Meanwhile, daidzein, the other primary isoflavone, promotes in vitro cellular attachment and enhances viability and proliferation of human fetal osteoblast cell (hFOB). Furthermore, controlled release of genistein, daidzein, and glycitein from 3DP TCP scaffold demonstrates improved hFOB cell proliferation, viability, and differentiation in a dynamic flow-perfusion bioreactor, which is utilized to better simulate the clinical microenvironment.
Finally, in vivo H&E staining confirms controlled co-delivery of genistein-daidzein-glycitein from 3DP scaffold carefully modulated neutrophil recruitment to the surgery site after 24 h of implantation in a rat distal femur model. These results advance our understanding towards multipronged therapeutic approaches utilizing synthetic bone graft substitutes as a drug delivery vehicle, and more importantly, demonstrate the feasibility of localized tumor cell suppression and bone cell proliferation for post-surgical defect repair application.
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