Innovative drug administration

Microneedles enable painless drug delivery. 

The introduction of microneedle (MN)-assisted transdermal drug delivery (TDD) has brought about innovation and an alternative method for drug administration. Benefits associated with MN-based delivery of drug include minimal training for use and painless insertion with no side effects like swelling and lipodystrophy (painful lump formation under the skin) at the administering site, which is very common in subcutaneous administration. 

An illustration of microneedle array patch inserted into the skin

An analysis of market trends indicates the microneedle-based drug delivery systems were leaning toward a billion-dollar market by the year 2020. Currently, North America is the largest market for microneedle medication delivery devices. By the end of 2030, it is anticipated to account for more than 70% of the market, with Europe. Over the next ten years, East Asia is expected to have the fastest growth rate in the area. The competition is getting intense as major market participants focus on expanding their markets through licensing and distribution rights. 

Today, production-scale manufacturing facilities are only available for microneedle array patch (MAP) products used in cosmetics. Preclinical and clinical research is being conducted on MAPs to administer drugs and vaccines, and commercial-scale production of pharmaceutical MAPs is still in its early stages. 

With the ongoing commercialization of microneedles, there is a greater need to address the challenges associated with their translation from the laboratory to the end user. The future development of the market for microneedle drug delivery systems is also likely to be impacted by shifting regulatory dynamics. For instance, the US Food and Drug Administration (FDA) halted Zosano Pharma's clinical trial of Zolmitriptan with a microneedle drug delivery device. This is after they discovered irregularities in drug distribution. Clinical trials are currently being conducted in humans to assess the efficacy and safety of transdermal insulin delivery through microneedles and patches.

The diabetes pandemic 

Diabetes mellitus is characterized by hyperglycemia or an excess of glucose in the bloodstream.

Its chief cause is insulin insufficiency or inappropriate insulin utilization in the body. A recently published study by the international diabetes federation highlighted that around 537 million people were suffering from diabetes in 2021 worldwide, and this number is expected to reach 783 million by 2045. 

According to the report published by the American Diabetes Association (ADA), diabetes can significantly raise the odds of severe and even fatal COVID-19 symptoms in people infected with the new coronavirus. For this reason, control of diabetes is a priority area as a part of the UN's Sustainable Development Goal 3 - to ensure healthy lives and well-being for all. For people living with diabetes, access to affordable treatment, including effective insulin delivery, is critical to their survival.

The most commonly used route of insulin administration among diabetic patients is subcutaneous insulin injections, which have several demerits like inherent poor patient compliance with injections, occasional hypoglycemia, and a risk of infection at the injection sites. This effect is more problematic in the pediatric population suffering from diabetes, posing a serious clinical challenge. Therefore, scientists have been trying to develop MN-based minimally invasive or non-invasive insulin delivery methods. 

Maintaining continuous delivery of insulin

It is more challenging to maintain the continuous delivery of insulin in a therapeutically relevant amount with microneedles than with hypodermic needles. 

Due to the microneedles’ physicochemical and skin parameters achieving the desired insulin transport rate is difficult. There is a variation in the skin properties based on age, sex, and ethnicity, which needs to be considered before using microneedles. Skin viscoelasticity and hydration (skin water content) for different age groups affect insulin delivery (for example, children’s skin is much thinner with less water content). 

It is pertinent to note that the microneedle used for adults cannot be used directly with the pediatric population. Therefore, the relation between the microneedle and skin properties needs to be better understood. Effective insertion of microneedles into the skin is the most critical aspect to achieve drug transport through this mechanism.

The UK's Engineering and Physical Sciences Research Council (EPSRC) has provided funding for a £1.2 million project on optimization of microneedle insertion. The project aims to expedite the development of microneedles. Researchers are also trying to transport insulin using microneedle-assisted oral drug delivery devices. 

Robert S. Langer and MIT researchers are developing ingestible, self-orienting devices with microneedles to inject insulin directly into the stomach lining. In a study with pigs, the bioavailability of insulin delivered with these devices was more than 50%. Langer’s lab has collaborated with researchers at Novo Nordisk to develop the devices.  

The need for software simulation platforms

Researchers have recently tried to conduct modeling and simulation studies on microneedles. 

Development of these injectable devices will require a proper understanding of the fluid dynamics involved, which can be answered through modeling studies. With the ongoing focus on digital twin platforms, it would be possible to design microneedle array patches based on patient requirements in the future. 

Further, mechanical analysis of repeated microneedle administration into the skin and its impact can be answered computationally by performing simulation studies on artificial skin models. Such simulation platforms will be helpful for pharmaceutical and biotechnological industries focusing on microneedle-based TDD systems.

The next era of injections is the painless, minimally invasive microneedles. 

Amongst the broad spectrum of injectables that microneedles can potentially cater to, insulin is a prominent one. For microneedle-based insulin injections to commercially scale, there is a need to understand the relation between skin properties and microneedles across age and ethnicity. 

Modeling and simulation studies in this space are active research areas that several research organizations and companies are pursuing. These studies and techniques help researchers and designers evaluate the performance of various designs and configurations of microneedle-based drug delivery systems under different conditions without conducting physical experiments. This allows them to identify potential problems and optimize the design of these systems before they are tested on humans, reducing the risk of failure in clinical trials. The maturity in designing such simulation platforms will accelerate the adoption and scale of microneedles for insulin delivery and other drug delivery applications. As the simulation platforms become sophisticated, researchers and designers will find it easier to evaluate and optimize new designs for microneedle-based drug delivery systems.

The author would like to thank Prateek Ranjan Yadav for his significant contribution to this research-led article. Prateek holds a PhD in Chemical Engineering from IIT Delhi and is currently pursuing an internship with TCS.