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Microneedles (MNs) have been used to deliver drugs for over two decades. These platforms have been proven to increase transdermal drug delivery efficiency dramatically by penetrating restrictive tissue barriers in a minimally invasive manner. While much of the early development of MNs focused on transdermal drug delivery, this technology can be applied to a variety of other non-transdermal biomedical applications. Several variations, such as multi-layer or hollow MNs, have been developed to cater to the needs of specific applications. The heterogeneity in the design of MNs has demanded similar variety in their fabrication methods; the most common methods include micromolding and drawing lithography. Numerous materials have been explored for MN fabrication which range from biocompatible ceramics and metals to natural and synthetic biodegradable polymers. Recent advances in MN engineering have diversified MNs to include unique shapes, materials, and mechanical properties that can be tailored for organ-specific applications. In this review, we discuss the design and creation of modern MNs that aim to surpass the biological barriers of non-transdermal drug delivery in ocular, vascular, oral, and mucosal tissue.

Closure of ocular wounds after an accident or surgery is typically performed by suturing, which is associated with numerous potential complications, including suture breakage, inflammation, secondary neovascularization, erosion to the surface and secondary infection, and astigmatism; for example, more than half of post-corneal transplant infections are due to suture related complications. Tissue adhesives provide promising substitutes for sutures in ophthalmic surgery. Ocular adhesives are not only intended to address the shortcomings of sutures, but also designed to be easy to use, and can potentially minimize post-operative complications. Herein, recent progress in the design, synthesis, and application of ocular adhesives, along with their advantages, limitations, and potential are discussed. This review covers two main classes of ocular adhesives: (1) synthetic adhesives based on cyanoacrylates, polyethylene glycol (PEG), and other synthetic polymers, and (2) adhesives based on naturally derived polymers, such as proteins and polysaccharides. In addition, different technologies to cover and protect ocular wounds such as contact bandage lenses, contact lenses coupled with novel technologies, and decellularized corneas are discussed. Continued advances in this area can help improve both patient satisfaction and clinical outcomes.

Topical administration of drugs and growth factors in a controlled fashion can improve the healing process during skin disorders and chronic wounds. To achieve this goal, a dermal patch is engineered that utilizes thermoresponsive drug microcarriers encapsulated within a hydrogel layer attached to a flexible heater with integrated electronic heater control circuitry. The engineered patch conformally covers the wound area and enables controlled drug delivery by electronically adjusting the temperature of the hydrogel layer. The drugs are encapsulated inside microparticles in order to control their release rates. These monodisperse thermoresponsive microparticles containing active molecules are fabricated using a microfluidic device. The system is used to release two different active molecules with molecular weights similar to drugs and growth factors and their release profiles are characterized. This platform is a key step towards engineering smart and closed loop systems for topical applications.

Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine's extremely short half-life in human blood (

Abstract: This study reports the development of a microfluidic system capable of repeated infusions of anti‐inflammatory factors post‐implantation for use as a coating for neural probes. This system consists of a microchannel in a thin gelatin methacryloyl–polyethylene glycol composite hydrogel surrounded by a porous polydimethylsiloxane membrane, where the hydrogel can be dried to increase the stiffness for easy insertion. Reswelling allows the perfusion of interleukin (IL)‐4 and dexamethasone as anti‐inflammatory factors through the channel with minimal burst release and significant amounts of IL‐4 are observed to release for up to 96 h post‐infusion. Repeated injections of IL‐4 increase the ratio of prohealing M2 versus proinflammatory M1 phenotypes of macrophages encapsulated in the hydrogel by sixfold compared with a single injection, over a 2‐week period. These repeated infusions also significantly downregulate the expression of inflammatory markers tumor necrosis factor‐α and IL‐6 in astrocytes encapsulated in hydrogel. To demonstrate the system as a coating of neural probes for in vivo applications, a prototype device is further fabricated, where a thin dual‐layered microfluidic system is integrated onto a metal probe. Such a drug delivery system can help reduce the formation of a glial scar around neural probes. [ABSTRACT FROM AUTHOR]

With the advent of technology, the role of nanomaterials in medicine has grown exponentially in the last few decades. The main advantage of such materials has been exploited in drug delivery applications, due to their effective targeting that in turn reduces systemic toxicity compared to the conventional routes of drug administration. Even though these materials offer broad flexibility based on targeting tissue, disease, and drug payload, the demand for more effective yet highly biocompatible nanomaterial-based drugs is increasing. While therapeutically improved and safe materials have been introduced in nanomedicine platforms, issues related to their degradation rate and bio-distribution still exist, thus making their successful translation to clinical application very challenging. Researchers are constantly improving upon novel nanomaterials that are safer and more effective not only as therapeutic agents but as diagnostic tools as well, making the research in the field of nanomedicine ever more fascinating. In this review, the stress has been made on the evolution of nanomaterials that are under different stages of clinical trials or have been approved by the United States Food and Drug Administration (FDA). [ABSTRACT FROM AUTHOR]

Millions of people worldwide suffer from debilitating, progressive, and often permanent loss of vision without any viable treatment options. The complex physiological barriers of the eye contribute to the difficulty in developing novel therapies by limiting our ability to deliver therapeutics in a sustained and controlled manner; especially when attempting to deliver drugs to the posterior eye or trying to regenerate the diseased retina. Cell-based therapies offer a significant potential advancement in these situations. In particular, encapsulating, or immunoisolating, cells within implantable, semi-permeable membranes has emerged as a clinically viable means of delivering therapeutic molecules to the eye for indefinite periods of time. The optimization of encapsulation device designs is occurring together with refinements in biomaterials, genetic engineering, and stem-cell production, yielding, for the first time, the possibility of widespread therapeutic use of this technology. Here, we highlight the status of the most advanced and widely explored iteration of cell encapsulation with an eye toward translating the potential of this technological approach to the medical reality. [ABSTRACT FROM AUTHOR]

Chronic, non-healing wounds place a significant burden on patients and healthcare systems, resulting in impaired mobility, limb amputation, or even death. Chronic wounds result from a disruption in the highly orchestrated cascade of events involved in wound closure. Significant advances in our understanding of the pathophysiology of chronic wounds have resulted in the development of drugs designed to target different aspects of the impaired processes. However, the hostility of the wound environment rich in degradative enzymes and its elevated pH, combined with differences in the time scales of different physiological processes involved in tissue regeneration require the use of effective drug delivery systems. In this review, we will first discuss the pathophysiology of chronic wounds and then the materials used for engineering drug delivery systems. Different passive and active drug delivery systems used in wound care will be reviewed. In addition, the architecture of the delivery platform and its ability to modulate drug delivery are discussed. Emerging technologies and the opportunities for engineering more effective wound care devices are also highlighted. [ABSTRACT FROM AUTHOR]

Novel microfluidic tools allow new ways to manufacture and test drug delivery systems. Organ-on-a-chip systems — microscale recapitulations of complex organ functions — promise to improve the drug development pipeline. This review highlights the importance of integrating microfluidic networks with 3D tissue engineered models to create organ-on-a-chip platforms, able to meet the demand of creating robust preclinical screening models. Specific examples are cited to demonstrate the use of these systems for studying the performance of drug delivery vectors and thereby reduce the discrepancies between their performance at preclinical and clinical trials. We also highlight the future directions that need to be pursued by the research community for these proof-of-concept studies to achieve the goal of accelerating clinical translation of drug delivery nanoparticles. [ABSTRACT FROM AUTHOR]

Abstract: The rapid advancement of nanotechnology has raised the possibility of using engineered nanoparticles that interact within biological environments for treatment of diseases. Nanoparticles interacting with cells and the extracellular environment can trigger a sequence of biological effects. These effects largely depend on the dynamic physicochemical characteristics of nanoparticles, which determine the biocompatibility and efficacy of the intended outcomes. Understanding the mechanisms behind these different outcomes will allow prediction of the relationship between nanostructures and their interactions with the biological milieu. At present, almost no standard biocompatibility evaluation criteria have been established, in particular for nanoparticles used in drug delivery systems. Therefore, an appropriate safety guideline of nanoparticles on human health with assessable endpoints is needed. In this review, we discuss the data existing in the literature regarding biocompatibility of nanoparticles for drug delivery applications. We also review the various types of nanoparticles used in drug delivery systems while addressing new challenges and research directions. Presenting the aforementioned information will aid in getting one step closer to formulating compatibility criteria for biological systems under exposure to different nanoparticles. [Copyright &y& Elsevier]