In recent years, many therapeutic peptides and proteins have come to market. While they are highly effective, these drugs must often be administered by IV or syringe injection. This complicates the administration process and can potentially affect patient compliance. At the same time, traditional transdermal patch technologies are only capable of delivering smaller, lipophilic molecules that diffuse through the stratum corneum and pass into systemic circulation. Few active pharmaceutical ingredients (APIs) are compatible with this method of delivery, particularly biopharmaceuticals. However, a new transdermal delivery system is showing promise for the administration of these drugs.
A hollow microstructured transdermal system (hMTS) uses hollow microstructures to penetrate the stratum corneum and provide fast, high-volume intradermal delivery of molecules traditionally restricted to syringe injection. The hMTS provides a comfortable and repeatable means of administering intradermal delivery of small-molecule salts, peptides, proteins (including antibodies), and molecules not readily compatible with oral, pulmonary, or traditional transdermal delivery technologies.
The device is designed for self-administration and integrates application of the small polymeric microstructures with a traditional glass API reservoir, along with a means of powering the intradermal delivery via a spring incorporated into the device. The disposable device is designed for home-based self administration to the upper arm or upper thigh (Figure 1).
The hMTS accesses the intradermal space, providing fast and efficient delivery into the systemic circulation. To overcome the barrier properties of the stratum corneum, the device utilizes biocompatible, medical-grade, polymeric microstructures.
These microstructures are modeled as mini hypodermic needles, 500 to 900 µm tall. Eighteen structures are configured across a 1 cm2 array, providing a diffuse area for intradermal infusion. Upon application, these structures penetrate the stratum corneum and pass through the epidermis into the dermis, well above the nerve endings that could cause discomfort. Following application, a relatively high volume of liquid formulation (0.5 to 1 mL) is delivered into the dermis, after which the device is removed. The device accommodates a traditional 1-mL glass cartridge as a reservoir for the formulation and is intended to be worn throughout the delivery period, which can range from 5 to 40 minutes depending on the formulation. An adhesive on the device enables it to stick to the skin during the required wear period. The depth of penetration associated with the hMTS integrated device ranges from 275 to 650 micrometers, depending on the length of the structures. Channels in each structure allow for fluid communication between the top and bottom of the array, offering a means for effectively and painlessly delivering liquid formulations into the skin.
Research shows the hMTS array has sufficient strength to penetrate the stratum corneum and sufficient flexibility to prevent fracture of the microstructures. The microstructures maintain integrity during insertion studies conducted in swine, hairless guinea pigs, and humans. Under extreme force, the microstructures will bend rather than fracture or break off, as might be expected from microstructures made of glass or metal.
The hMTS device has been used to provide efficient and fast in-vivo delivery of small-molecule salts and proteins, including high-molecular weight antibodies. hMTS delivery allows administration to be accomplished with the efficiency of a syringe, along with the patient-friendly characteristics of a transdermal patch (Figure 2). The system, which is not yet commercially available, has the potential to offer patients a means for simple, home-based self administration.
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2. David SP, Landis BJ, Adams ZH, Allen MG, Prausnitz MR. Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. J Biomech. 2004; 37:115-1163.
This article was published in Drug Discovery & Development magazine: Vol. 12, No. 10, November/December 2009, p. 34.
Filed Under: Drug Discovery