New Drug Delivery: 3D Printed Microneedles, Microfluidics, Porous Tantalum

Category: Blog,From Academia
blank blank Apr 09, 2021

In this issue of “From Academia”, we included three recent publications introducing innovative ways to deliver drugs. In the first article, the researchers demonstrated 3DMNMEMS, a novel device that combines 3D printing, microneedles (MNs), and Microelectromechanical Systems (MEMS). This device allows for versatile and controllable transdermal drug delivery, for example, the delivery of insulin. In the second article, the authors presented a one-step fabrication process of a microfluidic chip for drug dissolution assays based on 3D printing technology. The authors suggest that this method could be a reliable tool for drug release assays during the early research stages. The final publication is a review article focusing on past publications discussing the current applications of 3D-printed porous tantalum (3D-P-p-Ta), a novel drug delivery strategy, in drug delivery systems to repair hard tissue defects, as well as the limitations of existing data and potential future research directions.

From Academia” features recent, relevant, close to commercialization academic publications in the space of healthcare 3D printing, 3D bioprinting, and related emerging technologies. 

Email: Rance Tino (tino.rance@gmail.com) if you want to pen an Expert Corner blog for us or want to share relevant academic publications with us.

A novel 3D printed hollow microneedle microelectromechanical system for controlled, personalized transdermal drug delivery

Authored by Sophia N. Economidou, Jasim Uddin, Manual J. Marques, Dennis Douroumis, Wan Ting Sow, Huaqiong Li, Andrew Reid, James F.C. Windmill, Adrian Podoleanu. Additive Manufacturing. February 2021

a and c) CAD images of the ‘Bevel’ and ‘Ellipsis’ MN designs and respective cross-sections, b and d) SEM images of the 3D printed ‘Bevel’ and ‘Ellipsis’ MNs, e) SEM image of 4 MNs of the ‘Ellipsis’ design featuring dimensions. Copyright. Additive Manufacturing
a and c) CAD images of the ‘Bevel’ and ‘Ellipsis’ MN designs and respective cross-sections, b and d) SEM images of the 3D printed ‘Bevel’ and ‘Ellipsis’ MNs, e) SEM image of 4 MNs of the ‘Ellipsis’ design featuring dimensions. Copyright. Additive Manufacturing

Abstract:

The advancement of drug delivery devices is critical for the individualization of patient treatment and the improvement of healthcare. Here, we introduce the 3DMNMEMS, a novel device that combines 3D printing, microneedles (MNs) and Microelectromechanical Systems (MEMS), allowing versatile and controllable by the user transdermal drug delivery.

Hollow MNs were designed and 3D printed using Stereolithography, followed by integrating into a MEMS. By employing advanced imaging techniques, we monitored the distribution of liquid delivered by the device within skin tissue in real-time.

In vivo testing revealed that the delivery of insulin using the 3DMNMEMS achieved improved glycemic control to diabetic animals compared to subcutaneous injections. These results demonstrated the potential of the 3DMNMEMS as a universal transdermal drug delivery system for personalized care.

In vivo animal studies using a diabetic mice model for the treatment of diabetes using the 3DMNMEMS. a) No restriction of in-house movement 2 h prior to the experiment, b) blank application site after shaving, c) application of the 3D printed hollow MN patch, d) after insulin delivery using the 3DMNMEMS, e) after-piercing pores after treatment, f) No pores 5 min after treatment, g) plasma glucose levels after insulin administration, h) plasma insulin concentration after insulin administration. Copyright. Additive Manufacturing
In vivo animal studies using a diabetic mice model for the treatment of diabetes using the 3DMNMEMS. a) No restriction of in-house movement 2 h prior to the experiment, b) blank application site after shaving, c) application of the 3D printed hollow MN patch, d) after insulin delivery using the 3DMNMEMS, e) after-piercing pores after treatment, f) No pores 5 min after treatment, g) plasma glucose levels after insulin administration, h) plasma insulin concentration after insulin administration. Copyright. Additive Manufacturing

3D Printed Microfluidic Devices for Drug Release Assays

Authored by Benzion Amoyav, Yoal Goldstein, Eliana Steinberg, Ofra Benny. MDPI Pharmaceutics. 19 December 2020

Set-up of the two geometries of 3D printed drug release microfluidic chips connected to the pump. Parallel assays can be performed simultaneously for different chip geometries or for different drug formulations. Once assembled, the system is maintained in 37 °C.. Copyright MDPI Pharmaceutics
 Set-up of the two geometries of 3D printed drug release microfluidic chips connected to the pump. Parallel assays can be performed simultaneously for different chip geometries or for different drug formulations. Once assembled, the system is maintained in 37 °C.. Copyright MDPI Pharmaceutics

Abstract:

Microfluidics research for various applications, including drug delivery, cell-based assays, and biomedical research has grown exponentially. Despite this technology’s enormous potential, drawbacks include the need for multistep fabrication, typically with lithography.

We present a one-step fabrication process of a microfluidic chip for drug dissolution assays based on 3D printing technology. Doxorubicin porous and non-porous microspheres, with a mean diameter of 250µm, were fabricated using a conventional “batch” or microfluidic method, based on an optimized solid-in-oil-in-water protocol.

microfluidics
Overhead and side view schematic illustration of “V” (left) and “basket” (right) shape dissolution microfluidic
chip. The overall dimensions of the “V” and “basket” shape chips are identical with the main chamber width (A) of 16 mm,
length (B) of 20 mm, and height (C) of 600 m. Both chips contain a downstream trap of 38 teeth separated by 120 m gaps
(D). “V” trap design (left): includes two trapezoids separated by a 120 m gap (E). The V traps are lined in six rows of on and
off seven and eight traps, with a 1 mm gap between traps (F) and separated by 2.4 mm gap (G). “Basket” trap design (right): includes four rectangular teeth and additional two diagonal triangular teeth placed on both sides, separated by 120 m gaps (H) creating a 1.2 mm depth (I).

Microspheres fabricated with microfluidics system exhibited higher encapsulation efficiency and drug content as compared with batch formulations. We determined drug release profiles of microspheres in varying pH conditions using two distinct dissolution devices that differed in their mechanical barrier structures. The release profile of the “V” shape barrier was similar to that of the dialysis sac test and differed from the “basket” barrier design. Importantly, a cytotoxicity test confirmed the biocompatibility of the printed resin.

Finally, the chip exhibited high durability and stability, enabling multiple recycling sessions. We show how the combination of microfluidics and 3D printing can reduce costs and time, providing an efficient platform for particle production while offering a feasible cost-effective alternative to clean-room facility polydimethylsiloxane-based chip microfabrication.

Combined fluorescence and bright-filed microscopy image of a “V” and “basket” shape mechanical barrier. (A). Magnified view of a single polymeric microsphere captured in a ‘V’ trap design. (B1,B2). DOX-PMS captured in the “basket” trap design. (C). Trapped DOX-PMS in final pillar barriers before the outlet tube. (D) Lyophilized microfluidic based DOX-PMS.Copyright. MDPI Pharmaceutics
Combined fluorescence and bright-filed microscopy image of a “V” and “basket” shape mechanical barrier. (A). Magnified view of a single polymeric microsphere captured in a ‘V’ trap design. (B1,B2). DOX-PMS captured in the “basket” trap design. (C). Trapped DOX-PMS in final pillar barriers before the outlet tube. (D) Lyophilized microfluidic based DOX-PMS.Copyright. MDPI Pharmaceutics

3D-printed porous tantalum: recent application in various drug delivery systems to repair hard tissue defects

Authored by Long Hua,Ting Lei,Hu Qian,Yu Zhang,Yihe Hu &Pengfei Lei. Expert Opinion on Drug Delivery. November 2020

The flow gram of the study screening process. Copyright. Expert Opinion on Drug Delivery
The flow gram of the study screening process. Copyright. Expert Opinion on Drug Delivery

Abstract:

The treatment of hard tissue defects, especially those of bone and cartilage, induced by infections or tumors remains challenging. Traditional methods, including debridement with systematic chemotherapy, have shortcomings owing to their inability to eliminate infections and high systematic toxicity.

Drug delivery systems have advanced medical treatments, with the advantages of high local drug concentration, long drug-release period, and minimal systematic toxicity.

Due to its excellent biocompatibility, ideal mechanical property, and anti-corrosion ability, porous tantalum is one of the most preferable loading scaffolds. 3D printing allows for freedom of design and facilitates the production of regular porous implants with high repeatability. There are several reports on the application of 3D-P-p-Ta in drug delivery systems for the management of infection- or tumor-associated bone defects, yet, to the best of our knowledge, no reviews have summarized the current research progress.

This review comprehensively summarizes and discusses the current applications of 3D-printed porous tantalum (3D-P-p-Ta), a novel drug delivery strategy, in drug delivery systems to repair hard tissue defects, as well as the limitations of existing data and potential future research directions.

Different methods for drug delivery or treatment on porous tantalum. Copyright. Expert Opinion on Drug Delivery
Different methods for drug delivery or treatment on porous tantalum. Copyright. Expert Opinion on Drug Delivery

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