Devices and methods for enhanced microneedle penetration of biological barriers

Abstract

Microneedle devices and methods of use thereof are provided for the enhanced transport of molecules, including drugs and biological molecules, across tissue by improving the interaction of microneedles and a deformable, elastic biological barrier, such as human skin. The devices and methods act to (1) limit the elasticity, (2) adapt to the elasticity, (3) utilize alternate ways of creating the holes for the microneedles to penetrate the biological barrier, other than the simply direct pressure of the microneedle substrate to the barrier surface, or (4) any combination of these methods. In preferred embodiments for limiting the elasticity of skin, the microneedle device includes features suitable for stretching, pulling, or pinching the skin to present a more rigid, less deformable, surface in the area to which the microneedles are applied (i.e. penetrate). In a preferred embodiments for adapting the device to the elasticity of skin, the device comprising one or more extensions interposed between the substrate and the base end of at least a portion of the microneedles.

Description

BACKGROUND OF THE INVENTION [0001] This invention is generally in the field of devices for the transport of therapeutic or biological molecules across tissue barriers, such as for drug delivery or sampling of biological fluids. [0002] Numerous drugs and therapeutic agents have been developed in the battle against disease and illness. However, a frequent limitation of these drugs is their delivery: how to transport drugs across biological barriers in the body (e.g., the skin, the oral mucosa, the blood-brain barrier), which normally do not transport drugs at rates that are therapeutically useful or optimal. [0003] Drugs are commonly administered orally as pills or capsules. However, many drugs cannot be effectively delivered in this manner, due to degradation in the gastrointestinal tract and / or elimination by the liver. Moreover, some drugs cannot effectively diffuse across the intestinal mucosa. Patient compliance may also be a problem, for example, in therapies requiring that pill...

AI Technical Summary

Benefits of technology

[0014] Microneedle devices and methods of use thereof are provided for the enhanced transport of molecules, including drugs and biological molecules, across tissue by improving the interaction of an array of microneedles and a deformable, elastic biological barrier, such as human skin. The devices and methods act to (1) limit the elasticity, (2) adapt to the elasticity, (3) utilize alternate ways of creating the holes for the microneedles to penetrate the biological barrier, other than the simply direct pressure of the microneedle substrate to the barrier surface, or (4) any combination of these methods.

[0015] In preferred embodiments for limiting the elasticity of skin, the microneedle device includes features suitable for stretching, pulling, or pinching the skin to present a more rigid, less deformable, surface in the area to which the microneedles are applied (i.e. penetrate). For example, a vacuum can be applied to the area of the skin at the site of microneedle application to pull it taut and / or pull the skin onto the tips of the microneedles. Alternatively or in addition, the elasticity of skin can be reduced by applying a thin film or membrane over the skin surface at the site of application, so as to keep the skin tight, limiting the ability of the skin to stretch at the application site. The microneedles are then pushed through the film or membrane and into the skin.

[0016] In preferred embodiments for adapting the device to the elasticity of skin, the microneedles of the device include individual extensions or are provided in a curved three dimensional array, for example, by using a flexible substrate and / or varying the height of the microneedles in the array. In another embodiment, the microneedles are applied to the skin surface at an increased velocity, thereby reducing the time available for the stratum corneum and underlying tissues to deform from contact with the tips or entire length of the microneedles.

Problems solved by technology

However, a frequent limitation of these drugs is their delivery: how to transport drugs across biological barriers in the body (e.g., the skin, the oral mucosa, the blood-brain barrier), which normally do not transport drugs at rates that are therapeutically useful or optimal.

However, many drugs cannot be effectively delivered in this manner, due to degradation in the gastrointestinal tract and / or elimination by the liver.

Moreover, some drugs cannot effectively diffuse across the intestinal mucosa.

Patient compliance may also be a problem, for example, in therapies requiring that pills be taken at particular intervals over a prolonged time.

While effective for this purpose, needles generally cause pain; local damage to the skin at the site of insertion; bleeding, which increases the risk of disease transmission; and a wound sufficiently large to be a site of infection.

The needle technique also is undesirable for long term, controlled continuous drug delivery.

Similarly, current methods of sampling biological fluids are invasive and suffer from the same disadvantages.

No alternative methodologies are currently in use.

Proposed alternatives to the needle require the use of lasers or heat to create a hole in the skin, which is inconvenient, expensive, or undesirable for repeated use.

However, this method is not useful for many drugs, due to the poor permeability (i.e. effective barrier properties) of the skin.

Few drugs have the necessary physiochemical properties to be effectively delivered through the skin by passive diffusion.

While providing varying degrees of enhancement, these techniques are not suitable for all types of drugs, failing to provide the desired level of delivery.

In some cases, they are also painful and inconvenient or impractical for continuous controlled drug delivery over a period of hours or days.

Certain embodiments of the device were found to readily penetrate skin samples in in vitro experiments, but not always provide uniform or complete insertion of the microneedles into some areas of the skin in vivo, as the stratum corneum and underlying tissues are highly deformable and elastic over much of the body.

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