Drug Delivery Microsystems Research Articles

A microexplosive shockwave-based drug delivery microsystem for treating hard-to-reach areas in the human body

Implantable drug-delivery microsystems have the capacity to locally meet therapeutic requirements by maximizing local drug efficacy and minimizing potential side effects. The internal organs of the human body including the esophagus, gastrointestinal tract, and respiratory tract, with anfractuos contours, all manifest with endoluminal lesions often located in a curved or zigzag area. The ability of localized drug delivery for these organs using existing therapeutic modalities is limited. Spraying a drug onto these areas and using the adhesion and water absorption properties of the drug powder to attach to lesion areas can provide effective treatment. This study aimed to report the development and application of microsystems based on microshockwave delivery of drugs. The devices comprised a warhead-like shell with a powder placed at the head of the device and a flexible rod that could be inserted at the tail. These devices had the capacity to deposit drugs on mucous membranes in curved or zigzag areas of organs in the body. The explosive impact characteristics of the device during drug delivery were analyzed by numerical simulation. In the experiment of drug delivery in pig intestines, we described the biosafety and drug delivery capacity of the system. We anticipate that such microsystems could be applied to a range of endoluminal diseases in curved or zigzag regions of the human body while maximizing the on-target effects of drugs.

Microelectromechanical Systems Based on Magnetic Polymer Films

Microelectromechanical systems (MEMS) have been increasingly used worldwide in a wide range of applications, including high tech, energy, medicine or environmental applications. Magnetic polymer composite films have been used extensively in the development of the micropumps and valves, which are critical components of the microelectromechanical systems. Based on the literature survey, several polymers and magnetic micro and nanopowders can be identified and, depending on their nature, ratio, processing route and the design of the device, their performances can be tuned from simple valves and pumps to biomimetic devices, such as, for instance, hearth ventricles. In many such devices, polymer magnetic films are used, the disposal of the magnetic component being either embedded into the polymer or coated on the polymer. One or more actuation zones can be used and the flow rate can be mono-directional or bi-directional depending on the design. In this paper, we review the main advances in the development of these magnetic polymer films and derived MEMS: microvalve, micropump, micromixer, microsensor, drug delivery micro-systems, magnetic labeling and separation microsystems, etc. It is important to mention that these MEMS are continuously improving from the point of view of performances, energy consumption and actuation mechanism and a clear tendency in developing personalized treatment. Due to the improved energy efficiency of special materials, wearable devices are developed and be suitable for medical applications.

A 3D-Printed Modular Microreservoir for Drug Delivery.

Reservoir-based drug delivery microsystems have enabled novel and effective drug delivery concepts in recent decades. These systems typically comprise integrated storing and pumping components. Here we present a stand-alone, modular, thin, scalable, and refillable microreservoir platform as a storing component of these microsystems for implantable and transdermal drug delivery. Three microreservoir capacities (1, 10, and 100 µL) were fabricated with 3 mm overall thickness using stereolithography 3D-printing technology, enabling the fabrication of the device structure comprising a storing area and a refill port. A thin, preformed dome-shaped storing membrane was created by the deposition of parylene-C over a polyethylene glycol sacrificial layer, creating a force-free membrane that causes zero forward flow and insignificant backward flow (2% of total volume) due to membrane force. A septum pre-compression concept was introduced that enabled the realization of a 1-mm-thick septa capable of ~65000 leak-free refill punctures under 100 kPa backpressure. The force-free storing membrane enables using normally-open micropumps for drug delivery, and potentially improves the efficiency and precision of normally-closed micropumps. The ultra-thin septum reduces the thickness of refillable drug delivery devices, and is capable of thousands of leak-free refills. This modular and scalable device can be used for drug delivery in different laboratory animals and humans, as a sampling device, and for lab-on-a-chip and point-of-care diagnostics applications.

Motion Control of Urea-Powered Biocompatible Hollow Microcapsules.

The quest for biocompatible microswimmers powered by compatible fuel and with full motion control over their self-propulsion is a long-standing challenge in the field of active matter and microrobotics. Here, we present an active hybrid microcapsule motor based on Janus hollow mesoporous silica microparticles powered by the biocatalytic decomposition of urea at physiological concentrations. The directional self-propelled motion lasts longer than 10 min with an average velocity of up to 5 body lengths per second. Additionally, we control the velocity of the micromotor by chemically inhibiting and reactivating the enzymatic activity of urease. The incorporation of magnetic material within the Janus structure provides remote magnetic control on the movement direction. Furthermore, the mesoporous/hollow structure can load both small molecules and larger particles up to hundreds of nanometers, making the hybrid micromotor an active and controllable drug delivery microsystem.

In vitro assessment of biopolymer-modified porous silicon microparticles for wound healing applications

The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue’s integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications.

Dynamic curvature control of rolled-up metal nanomembranes activated by magnesium

Dynamic curvature control of rolled-up metal nanomembranes using an active magnesium layer design is implemented in bio-oriented conditions to realize shape transformation of expansion, shrinking, un-rolling and re-rolling. The tube integrated with a catalytic Pt layer is proposed for a new type of smart drug delivery microsystem.

Numerical modeling of a novel degradable drug delivery system with microholes

Based on UV-LIGA technology, a novel drug delivery microsystem is proposed to eliminate the time lag in initial drug release. With proper microholes in bonding membrane, the drug release rate can be controlled at a stable level in the whole release process. This microsystem is fabricated by degradable polymer and suitable for subcutaneous implants. As a significant parameter, the demarcation time of polymer absorption/erosion is estimated by comparing the experimental results of polymer erosion and in vitro release. By considering diffusion, swelling and erosion mechanisms simultaneously, a numerical drug releasing model is developed to investigate the effect of microholes on drug release and impact factors of linear drug releasing. The simulation results show that the microholes are beneficial to eliminate the time lag, and furthermore, the area of microholes and the initial drug loading have great impact on the release time and the linear drug release rate.

Intelligent intraoral drug delivery microsystem

The authors report on the concept and development of an intelligent intraoral drug delivery microsystem, that provides an alternative approach for the treatment of addiction and chronic diseases. The drug delivery system (DDS) comprises a medication replacement reservoir, a medication release mechanism, a built-in intelligence, a remote control, microsensors, and microactuators. It is thus able to release the medication in a controlled manner according to the patient needs. The emphasis of this article is on the application of sensors and microfluidic components in a real microsystem and also showing some details of two system components, namely, the osmotic pump and the flow sensor. The motivation for the microfluidic approach, the concept of the DDS, the requirements for this specific application, and the arising problems will be presented and discussed. Regarding the sensors and actuators, the problems mainly concern size and power consumption. A major challenging aspect of microfluidic component development is to avoid clogging of small channels because of particles and recrystallization of saturated fluids.

Integrated microsystems for controlled drug delivery

Efficient drug delivery and administration are needed to realize the full potential of molecular therapeutics. Integrated microsystems that incorporate extremely fast sensory and actuation capabilities can fulfill this need for efficient drug delivery tools. Photolithographic technologies borrowed from the semiconductor industry enable mass production of such microsystems. Rapid prototyping allows for the quick development of customized devices that would accommodate for diverse therapeutic requirements. This paper reviews the capabilities of existing microfabrication and their applications in controlled drug delivery microsystems. The next generation of drug delivery systems—fully integrated and self-regulating—would not only improve drug administration, but also revolutionize the health-care industry.