Intra-Dermal drug delivery: Opportunities and Challenges?

• Fabrication of 3D printed novel microneedle arrays via stereolithgraphy using a biocompatible resin
• Design of microneedle arrays for high drug delivery through the skin
• Use of inkjet printing technology to deposit anticancer drugs on 3D printed microneedles for rapid release
• The printability and skin piercing capacity of 3D printed MNs is discussed
• In vivo pre-clinical trials demonstrated high anticancer activity and tumour regression.

Compared with DMNs in the same geometries, the PCMs delivered the required dose in a more condensed form without considering insulin solubility and degradation during the fabrication process. Moreover, PCMs showed enhanced long-term stability and prolonged release kinetics, which could be utilized to treat diabetes without apparent safety issues. This implantable PCM technique will greatly impact the future of transdermal drug delivery systems because it is applicable to any type of therapeutic available in a dry powder formulation for a wide variety of biomedical applications.

A drug-loaded microrobotic needle effectively targets and remains attached to cancerous tissue in lab experiments without needing continuous application of a magnetic field, allowing more precise drug delivery. The details were published by researchers at DGIST's Microrobot Research Center in Korea and colleagues in the journal Advanced Healthcare Materials.

A team at the University of Pittsburgh School of Medicine have now developed a microneedle array patch that can carry live or attenuated viral vectors, as well as adjuvant compounds to boost vaccine effectiveness. The patch is very impressive at activating a strong immune response.

In conclusion, we demonstrate that a single microneedle vaccination in the skin with stabilized influenza VLPs provides protection superior to that of conventional intramuscular immunization. The stabilization of influenza vaccines as measured by retention of the HA functional activity is an important parameter in predicting vaccine efficacy. HA stabilization, combined with vaccination via the skin using vaccine formulated as a solid-microneedle patch (MN+T), exhibited some advantages in the primary antibody response following an equivalent single-dose vaccination and showed more pronounced differences after lethal virus challenge.

Herein, we provide an overview on the progress in microneedle-based transdermal biosensors. It covers all the main aspects of the field, including design philosophy, material selection, and working mechanisms as well as the utility of the devices. We also discuss lessons from the past, challenges of the present, and visions for the future on translation of these state-of-the-art technologies from the bench to the bedside.

Longitudinal in vivo imaging using a smartphone adapted to detect NIR light demonstrated that microneedle-delivered QD patterns remained bright and could be accurately identified using a machine learning algorithm 9 months after application. In addition, codelivery with inactivated poliovirus vaccine produced neutralizing antibody titers above the threshold considered protective. These findings suggest that intradermal QDs can be used to reliably encode information and can be delivered with a vaccine, which may be particularly valuable in the developing world and open up new avenues for decentralized data storage and biosensing.

The results showed that the tertiary structure of BSA was well maintained in both PLGA and PVP layers while the secondary structures were slightly changed during microneedle fabrication. In vitro release studies showed that over 60% of BSA in the PLGA layer was released within 1 h, followed by continuous slow release over the course of the experiments (7 days), while BSA in the PVP layer was completely released within 0.5 h. The initial burst of BSA from PLGA was further controlled by depositing a blank PLGA layer prior to forming the PLGA layer containing BSA. The blank PLGA layer acted as a diffusion barrier, resulting in a reduced initial burst. The formation of the PLGA diffusion barrier was visualized using confocal microscopy. Our results suggest that the spray-formed multilayer microneedles could be an attractive transdermal drug delivery system that is capable of modulating a drug release profile.

The maximal capacity of lidocaine-HCl in the Li-DMN patch was 331.20 ± 6.30 µg. The cytotoxicity of the dissolving microneedle to neuronal cells was negligible under an effective dose of lidocaine for 18 h. Electrophysiological recordings verified the inhibitory effect of the voltage-gated sodium channel current by the Li-DMN patch in vitro. A skin reaction to the edema test and histologic analysis of the rats’ ears after application of the Li-DMN patch were negligible. Also, the application of the Li-DMN patch reduced the nocifensive behavior of the rats almost immediately. In conclusion, the dissolving microneedle patch with carboxymethyl cellulose is a promising candidate method for the painless delivery of lidocaine-HCl.

Our method utilizes stereolithography 3D-printing and pushes its boundaries (achieving print resolutions below the full width half maximum laser spot size resolution) to create complex architectures with lower cost and higher print speed and throughput than previously reported methods. To demonstrate a potential application, a microfluidic-enabled microneedle architecture was printed to render hydrodynamic mixing and transdermal drug delivery within a single device. The presented architectures can be adopted in future biomedical devices to facilitate new modes of operations for transdermal drug delivery applications such as combinational therapy for preclinical testing of biologic treatments.

The skin is an ideal vaccination site containing an innate immune network that is exquisitely responsive to environmental stimuli and capable of inducing a proinflammatory microenvironment, favoring the generation of strong and long-lasting adaptive immunity (Kabashima et al., 2019; Kashem et al., 2017).

A team of researchers from MIT has developed a precision microinjection procedure that can help deliver water, nutrients, and medicine to plants struggling against diseases affecting their circulatory systems. Such plagues are untreatable by normal pesticides, the team explains, and there are already outbreaks in several areas of the world affecting crops such as oranges, olives, and bananas.

We demonstrated that the new fabrication approach enables creating dissolvable MNAs with diverse geometries and from different materials reproducibly. We also demonstrated the application of MNAs for precise and specific delivery of biomolecules to skin microenvironments in vitro and in vivo.

Now, engineers have come out with the offer to make as many of a relatively new and efficient type of drug/vaccine delivery systems as are needed for research on vaccine development and the treatment of this condition to continue.

Coronaviruses pose a serious threat to global health as evidenced by Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and COVID-19. SARS Coronavirus (SRS-CoV), MERS Coronavirus (MERS-CoV), and the novel coronavirus, previously dubbed 2019-nCoV, and now officially named SARS-CoV-2, are the causative agents of the SARS, MERS, and COVID-19 disease outbreaks, respectively. Safe vaccines that rapidly induce potent and long-lasting virus-specific immune responses against these infectious agents are urgently needed. The coronavirus spike (S) protein, a characteristic structural component of the viral envelope, is considered a key target for vaccines for the prevention of coronavirus infection.

As part of the work, the researchers engineered a thumb-sized patch containing more than 200 hollow-structured microneedles. They used the patch to deliver cold atmospheric plasma, a unique type of ionized gas that can kill cancer cells, to tumour tissues in mice with melanoma. The microneedles also deliver immunotherapeutics – immune checkpoint inhibitors – directly to the tumour.

Microneedles (MNs) are playing an increasingly important role in biomedical applications, where minimally invasive methods are being developed that require imperceptible tissue penetration and drug delivery. To improve the integration of MNs in microelectromechanical devices, a high‐resolution 3D printing technique is implemented. A reservoir with an array of hollow MNs is produced. The flow rate through the MNs is simulated and measured experimentally.