Transdermal Delivery of siRNA through Microneedle Array

Organic and inorganic nanoparticles (NPs) have shown promising outcomes in transdermal drug delivery. NPs can not only enhance the skin penetration of small/biomacromolecule therapeutic agents but can also impart control over drug release or target impaired tissue. Thanks to their unique optical, photothermal, and superparamagnetic features, NPs have been also utilized for the treatment of skin disorders, imaging, and biosensing applications. Despite the widespread transdermal applications of NPs, their delivery across the stratum corneum, which is the main skin barrier, has remained challenging. Microneedle array (MN) technology has recently revealed promising outcomes in the delivery of various formulations, especially NPs to deliver both hydrophilic and hydrophobic therapeutic agents. The present work reviews the advancements in the application of MNs and NPs for an effective transdermal delivery of a wide range of therapeutics in cancer chemotherapy and immunotherapy, photothermal and photodynamic therapy, peptide/protein vaccination, and the gene therapy of various diseases. In addition, this paper provides an overall insight on MNs’ challenges and summarizes the recent achievements in clinical trials with future outlooks on the transdermal delivery of a wide range of nanomedicines.

Download Full-text

Smartphone-powered iontophoresis-microneedle array patch for controlled transdermal delivery

Microsystems & Nanoengineering ◽

10.1038/s41378-020-00224-z ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Jingbo Yang ◽

Yanjun Li ◽

Rui Ye ◽

Ying Zheng ◽

Xiangling Li ◽

...

Keyword(s):

Transdermal Delivery ◽

Insulin Delivery ◽

Diabetic Rat ◽

Microneedle Array ◽

Control Drug ◽

Control Of Diabetes ◽

One Step ◽

Glycemic Regulation

AbstractThe incidence rate of diabetes has been increasing every year in nearly all nations and regions. The traditional control of diabetes using transdermal insulin delivery by metal needles is generally associated with pain and potential infections. While microneedle arrays (MAs) have emerged as painless delivery techniques, the integration of MA systems with electronic devices to precisely control drug delivery has rarely been realized. In this study, we developed an iontophoresis-microneedle array patch (IMAP) powered by a portable smartphone for the active and controllable transdermal delivery of insulin. The IMAP in situ integrates iontophoresis and charged nanovesicles into one patch, achieving a one-step drug administration strategy of “penetration, diffusion and iontophoresis”. The MA of the IMAP is first pressed on the skin to create microholes and then is retracted, followed by the iontophoresis delivery of insulin-loaded nanovesicles through these microholes in an electrically controlled manner. This method has synergistically and remarkably enhanced controlled insulin delivery. The amount of insulin can be effectively regulated by the IMAP by applying different current intensities. This in vivo study has demonstrated that the IMAP effectively delivers insulin and produces robust hypoglycemic effects in a type-1 diabetic rat model, with more advanced controllability and efficiency than delivery by a pristine microneedle or iontophoresis. The IMAP system shows high potential for diabetes therapy and the capacity to provide active as well as long-term glycemic regulation without medical staff care.

Download Full-text

Transdermal Delivery of Adipocyte Phospholipase A2 siRNA using Microneedles to Treat Thyroid Associated Ophthalmopathy-Related Proptosis

Cell Transplantation ◽

10.1177/09636897211010633 ◽

2021 ◽

Vol 30 ◽

pp. 096368972110106

Author(s):

Guiqin Liu ◽

Yan Deng ◽

Yi Song ◽

Yi Sui ◽

Juan Cen ◽

...

Keyword(s):

Adipose Tissue ◽

Phospholipase A2 ◽

Transdermal Delivery ◽

Sirna Delivery ◽

Microneedle Array ◽

Adipose Tissues ◽

Thyroid Associated Ophthalmopathy ◽

Organ Specific ◽

Adipocyte Cell ◽

Human And Mouse

Thyroid associated ophthalmopathy (TAO) is an organ-specific autoimmune disease occurring in patients with thyroid disease. Patients with TAO-related proptosis is largely due to excessive orbital adipose tissue Adipocyte phospholipase A2 (AdPLA) is one of the most important regulatory factors in adipocyte lipolysis, which may be associated with TAO-related proptosis. Thus, silencing AdPLA by RNA interference may be beneficial for the treatment of TAO. In this study, we sought to evaluate the efficiency of two types of microneedles to deliver siRNAs for silencing AdPLA. Our results showed that AdPLA mRNA was up-regulated in the orbit adipose tissues from TAO patients. Silence of AdPLA by siRNA can reduce lipid accumulation in both human and mouse adipocyte cell lines. Moreover, silence effects of silicon microneedle array patch-based and injectable microneedle device-based siRNA administration were examined at the belly site of the mice, and injectable microneedle device showed higher knockdown efficiency than silicon microneedle array patch. This study sets the stage not only for future treatment of TAO-related proptosis using AdPLA siRNA, but also provides the foundation for targeted siRNA delivery by using microneedles.

Download Full-text

An Overview of Microneedles: Types, Materials, Processes, Emerging Approach and Applications in Dermatology

Journal of University of Shanghai for Science and Technology ◽

10.51201/jusst/21/121038 ◽

2021 ◽

Vol 23 (12) ◽

pp. 401-416

Author(s):

Snehal S. Patil ◽

◽

Nikita S. Patil ◽

Umesh C. Suryawanshi ◽

Mr. Rohan R. Vakhariya ◽

...

Keyword(s):

Transdermal Delivery ◽

Clinical Medicine ◽

Global Market ◽

Technical Note ◽

Growth Hormones ◽

Microneedle Array ◽

Large Molecules ◽

Hydrophilic Nature ◽

Current Scenario ◽

Near Future

Drug delivery through the skin by transdermal patches has a long history. Subsequent growth of transdermal science proved prominent utility of transdermal systems meant for passive diffusion of the drug. It was followed by the development of Iontophoresis and Sonophoresis based transdermal delivery systems. Microneedle array has now caught attention of the investigators owing to its immense utility in transdermal delivery of very large molecules with ionic and hydrophilic nature. In this technical note, we present the current scenario, applications, and recent advances in microneedle array-based delivery of the most critical molecules through the skin. The application of microneedle has widely been investigated, and these technologies are being developed for the delivery of bio-therapeutics, biomacromolecules, insulin, growth hormones, immunobiologicals, proteins, siRNA and peptides. Potential of microneedles to transform the global transdermal market is highlighted in terms of the success rate of the microneedle technologies in clinical trials reaching to the global market. The arrival of the commercial microneedle-based products in the market is highly anticipated as they have potential to portray remarkable impact on clinical medicine in near future.

Download Full-text