MICRONEEDLE TECHNOLOGY - The New Potential of Microneedles for Biologics & Small Molecules

ABSTRACT

Traditional transdermal patches have been limited to use with a small range of molecules, which is unfortunate, given their patient-friendly features and ease of use. As the pharmaceutical industry continues to expand its offerings to include larger molecules and biologics, new transdermal platforms are also evolving. This article describes how microneedle technology is being applied in two new transdermal systems using solid and hollow microneedles. The solid and hollow microneedle transdermal systems, currently available for clinical trials, have the ability to deliver small molecules as well as biologics, opening up the potential for self-administration of a broad array of Active Pharmaceutical Ingredients (APIs).

INTRODUCTION

Expiring patents, the expanding biopharmaceutical market, and a growing focus on patient preference are all driving changes in drug delivery. For patients with chronic conditions, these changes are likely welcome, as noncompliance among this group has been estimated at 10%.^1-3

A delivery system that makes it easier for patients to self-administer medications and avoid traveling to a clinical setting for an injection or IV administration holds the potential to improve compliance and convenience. The transdermal patch provides a good example of such a delivery system. Delivery via traditional transdermal patch has been a well-liked option among both patients and providers for many years.⁴ Patches beat pulmonary, injection, and intranasal delivery methods in terms of comfort and convenience.

However, traditional patches are only suitable for smaller lipophilic molecules, which account for a very small portion of APIs. Research has continued on transdermal delivery to broaden its capabilities, as this method of delivery has unique advantages, including its rapid onset of action and ability to contribute to higher uptake efficiency.

Now, recent advances in transdermal technologies are making it possible to expand this patient-preferred delivery method to encompass both small and large molecules, including biologics. With these technologies, pharmaceutical companies gain new delivery methods for dermal skin targets or systemic distribution for drugs that enter the lymphatic system.

These advances utilize microneedles — polymeric microstructures — to conquer the limitations of the traditional transdermal patch. There are currently two types of microneedle devices under development.

SOLID MICRONEEDLES

This technology uses a coating of relatively potent molecules and peptides (up to 300 micrograms) that are dried on the tips of a microneedle array. When the patient applies the microneedle array patch with the 3M^TM Solid Microstructured Transdermal Systems (sMTS), the solid microneedles (of a set length between 250 micrometers to 700 micrometers tall) penetrate the stratum corneum and remain in the skin for a wear time ranging from 30 seconds to 10 minutes. During the wear time, the drug releases from the microneedles into the skin. This method of delivery holds great promise for vaccines because it is able to enhance their efficacy by targeting antigen-presenting cells within the skin. With the vaccine kept dry, the patch can be stored at room temperature. Solid microneedles can also potentially improve pharmacokinetics versus a subcutaneous injection for a variety of drugs, assuming the dried drug formulation is stable over time. The 3M sMTS system has been successfully used in Phase I and Phase II clinical trials.

HOLLOW MICRONEEDLES

As opposed to solid microneedles, which use dried API, hollow microneedles allow delivery of liquid formulations of up to 2 mL. This technology is compatible with small molecules as well as biologics, such as proteins and peptides. Hollow microneedles reach into the dermal layer of the skin, a highly vascularized area that makes it ideal for delivery of many treatments.

The 3M^TM Hollow Microstructured Transdermal System (hMTS) device is currently in clinical trials. The microneedles are located on a 1-cm² polymeric disk, with the specific arrangement of the microneedles adjustable based on drug formulation and targeted delivery site. The microneedle array is attached to a conventional glass cartridge via a sterile flow path. A mechanical spring powers delivery of the formulation from the cartridge through the microneedles. When applied, the microneedles penetrate through the stratum corneum and epidermis to reach into the dermis.

The device is capable of delivering volumes ranging from 0.5 mL to 2 mL, and is compatible with both viscous and non-viscous formulations, with viscous formulations potentially requiring a longer wear time. In hollow microneedle devices, formulations must be chemically compatible with the device, especially upon stability storage and during delivery. Additional physical compatibility considerations include whether drug molecules are able to withstand shear forces as they flow through the microneedles.

Developers are well aware that design of any new drug delivery device requires close adherence to regulatory requirements for patient-centric design and self-administration. Usability trials conducted on the hMTS have identified design improvements to make it more convenient for patients (especially patients with dexterity challenges) to self-administer. The device is designed in an easy-to-handle size and has a textured grip. Actuation is both visible and audible, as a click sounds when the device is activated. A status indicator window also helps patients see progress of the medication delivery. Features like these help improve patient confidence with self-administration.

SUMMARY

The treatment potential held by biologics and small molecules continues to drive innovations in the pharmaceutical industry. Microneedles provide a promising delivery method for these APIs, and the availability of both sMTS and hMTS for clinical trials moves the industry one step closer to offering a patient-friendly alternative to injections and IV administration.

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REFERENCES
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3. Devonshire V, Lapierre Y, Macdonell R, et al. The global adherence project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis. Eur J Neurol. 2011;18(1):69-77.
4. Frost & Sullivan. (2008, Feb). US Drug Delivery: Usage Patterns, Preferences and Opportunities in the US.

Dr. Lisa Dick is the MTS Technical Manager for 3M Drug Delivery Systems in St. Paul, MN. She earned her PhD in Chemistry from Northwestern University and completed her post-doctoral research at Princeton University focusing on Protein and Peptide Chemistry. Her research interests include development of inhalation and transdermal drug delivery systems.