Evolution of Transdermal Drug Delivery Devices and Novel Microneedle Technologies: A Historical Perspective and Review.

The history of transdermal drug delivery is as old as humankind. Transdermal drug delivery has undergone three generations of development; the third generation has involved the use of medical devices and instruments. This review provides a historical perspective on the primary approaches employed in the three generations of transdermal drug delivery. In addition, we explore some of the recently developed transdermal techniques that are deemed promising in the field of drug delivery. We discuss how advances in these techniques have led to the development of devices for the delivery of a therapeutically effective amount of drug across human skin and highlight the limitations of the first- and second-generation drug delivery tools. As such, a review of the performance of these techniques and the toxicity of the devices used in transdermal drug delivery are considered. In the last section of the review, a discussion of the fabrication and operation of different types of microneedles is presented. The applications of microneedles in the sensing and delivery of various therapeutic agents are described in detail. Furthermore, an overview of the efficacy of microneedles as emerging tools for the controlled release of drugs is presented.

Micromolding of Amphotericin-B-Loaded Methoxyethylene-Maleic Anhydride Copolymer Microneedles.

Biocompatible and biodegradable materials have been used for fabricating polymeric microneedles to deliver therapeutic drug molecules through the skin. Microneedles have advantages over other drug delivery methods, such as low manufacturing cost, controlled drug release, and the reduction or absence of pain. The study examined the delivery of amphotericin B, an antifungal agent, using microneedles that were fabricated using a micromolding technique. The microneedle matrix was made from GantrezTM AN-119 BF, a benzene-free methyl vinyl ether/maleic anhydride copolymer. The GantrezTM AN-119 BF was mixed with water; after water evaporation, the polymer exhibited sufficient strength for microneedle fabrication. Molds cured at room temperature remained sharp and straight. SEM images showed straight and sharp needle tips; a confocal microscope was used to determine the height and tip diameter for the microneedles. Nanoindentation was used to obtain the hardness and Young's modulus values of the polymer. Load-displacement testing was used to assess the failure force of the needles under compressive loading. These two mechanical tests confirmed the mechanical properties of the needles. In vitro studies validated the presence of amphotericin B in the needles and the antifungal properties of the needles. Amphotericin B GantrezTM microneedles fabricated in this study showed appropriate characteristics for clinical translation in terms of mechanical properties, sharpness, and antifungal properties.

Transdermal Polymeric Microneedle Sensing Platform for Fentanyl Detection in Biofluid.

Opioid drugs are extremely potent synthetic analytes, and their abuse is common around the world. Hence, a rapid and point-of-need device is necessary to assess the presence of this compound in body fluid so that a timely countermeasure can be provided to the exposed individuals. Herein, we present an attractive microneedle sensing platform for the detection of the opioid drug fentanyl in real serum samples using an electrochemical detection method. The device contained an array of pyramidal microneedle structures that were integrated with platinum (Pt) and silver (Ag) wires, each with a microcavity opening. The working sensor was modified by graphene ink and subsequently with 4 (3-Butyl-1-imidazolio)-1-butanesulfonate) ionic liquid. The microneedle sensor showed direct oxidation of fentanyl in liquid samples with a detection limit of 27.8 µM by employing a highly sensitive square-wave voltammetry technique. The resulting microneedle-based sensing platform displayed an interference-free fentanyl detection in diluted serum without conceding its sensitivity, stability, and response time. The obtained results revealed that the microneedle sensor holds considerable promise for point-of-need fentanyl detection and opens additional opportunities for detecting substances of abuse in emergencies.

Enhanced Vapor Transmission Barrier Properties via Silicon-Incorporated Diamond-Like Carbon Coating.

In this study, we describe reducing the moisture vapor transmission through a commercial polymer bag material using a silicon-incorporated diamond-like carbon (Si-DLC) coating that was deposited using plasma-enhanced chemical vapor deposition. The structure of the Si-DLC coating was analyzed using scanning electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, selective area electron diffraction, and electron energy loss spectroscopy. Moisture vapor transmission rate (MVTR) testing was used to understand the moisture transmission barrier properties of Si-DLC-coated polymer bag material; the MVTR values decreased from 10.10 g/m2 24 h for the as-received polymer bag material to 6.31 g/m2 24 h for the Si-DLC-coated polymer bag material. Water stability tests were conducted to understand the resistance of the Si-DLC coatings toward moisture; the results confirmed the stability of Si-DLC coatings in contact with water up to 100 °C for 4 h. A peel-off adhesion test using scotch tape indicated that the good adhesion of the Si-DLC film to the substrate was preserved in contact with water up to 100 °C for 4 h.

Physicochemical parameters that underlie inkjet printing for medical applications.

One of the most common types of 3D printing technologies is inkjet printing due to its numerous advantages, including low cost, programmability, high resolution, throughput, and speed. Inkjet printers are also capable of fabricating artificial tissues with physiological characteristics similar to those of living tissues. These artificial tissues are used for disease modeling, drug discovery, drug screening, and replacements for diseased or damaged tissues. This paper reviews recent advancements in one of the most common 3D printing technologies, inkjet dispensing. We briefly consider common printing techniques, including fused deposition modeling (FDM), stereolithography (STL), and inkjet printing. We briefly discuss various steps in inkjet printing, including droplet generation, droplet ejection, interaction of droplets on substrates, drying, and solidification. We also discuss various parameters that affect the printing process, including ink properties (e.g., viscosity and surface tension), physical parameters (e.g., internal diameter of printheads), and actuation mechanisms (e.g., piezoelectric actuation and thermal actuation). Through better understanding of common 3D printing technologies and the parameters that influence the printing processes, new types of artificial tissues, disease models, and structures for drug discovery and drug screening may be prepared. This review considers future directions in inkjet printing research that are focused on enhancing the resolution, printability, and uniformity of printed structures.

Inkjet dispensing technologies: recent advances for novel drug discovery.

INTRODUCTION: Inkjet-dispensing printing is a promising additive manufacturing method for pharmaceutical applications such as drug discovery. The unique advantages of this technology, including low cost, programmability, high resolution, high throughput, high speed, and biocompatibility, may reduce the financial resources needed to discover new drug candidates. Sophisticated and miniaturized assays have been developed to accomplish drug discovery and drug screening using modern inkjet dispensing printers. Areas covered: This paper reviews recent advancements in the field of inkjet printer technology for drug discovery. Various types of inkjet printers and their recent use for the drug discovery are summarized; physical and biological limitations of this technology are also examined. Furthermore, typical inks used in the inkjet printing technology are introduced. Expert opinion: Inkjet bioprinting technology is a promising tool for many biological and pharmaceutical applications. Several bottlenecks associated with this technology need to be addressed before commercialization. For example, sophisticated inks need to be synthesized to meet both biological and engineering restrictions. Further progress of parallel technologies will enhance the performance and functionality of the printers. It is also worth emphasizing that inkjet printing technologies must meet the requirement of regulatory agencies (e.g. the US Food & Drug Administration) for commercialization by the pharmaceutical industry.