Microneedle drug delivery systems
usually include hollow microneedle and solid microneedle technology, offer patient-friendly delivery solutions for vaccines or difficult-to-deliver biologics for particularly needle-phobic patients.
Hollow Microneedle Technology
Hollow microneedles function in much the same way as traditional hypodermic needles: through the distribution of an injectable drug through the needle and into the targeted tissue; however, in the case of microneedles, the drug is injected into the dermis rather than subcutaneous tissue or muscle. Hollow microneedles mitigate the need for drug reformulation, which means they can readily be used with most existing drugs and vaccines approved for the intradermal route of administration. These approved drugs will see a rapid path to commercial adoption of hollow microneedle-based injection systems. Drugs that are suitable, but not yet approved, for intradermal delivery, such as insulin, will require a combination product clinical trial before completely adopting hollow microneedle-based injection systems.
After work in the early 1990s on individual microneedles and individual rows of microneedles, the first two-dimensional hollow microneedle array was made from metal using a costly, non-reusable silicon mold. Most early microneedle devices were manufactured in silicon through technologies such as microelectromechanical systems (MEMS) manufacturing methods, including deep reactive ion etching (DRIE) and lithography. The goal was to create high aspect ratio, hollow core microneedles structures. The challenge in this manufacturing system lies primarily in the high cost of infrastructure and maintenance of the silicon manufacturing tools. Many of the microneedles that are currently being commercialized come from this costly manufacturing process, leading to difficulty in scaling and adoption. However, these structures are valuable tools in demonstrating the potential of microneedle technology and are largely still in use for research studies.
Solid Microneedle Technology
Solid microneedles were among the first to be developed. They are solid structures that puncture the skin while the drug is applied to the site of the puncture as a topical cream. This delivery method is simple and does not require significant training, thus simplifying the process for patients, but placing the burden of manufacturing and reformulation on pharmaceutical companies, as most injectable drugs would have to be recreated (and possibly re-approved by health agencies) as a cream or other topical solution. There are also drawbacks in delivering large doses of drugs to patients and sufficiently controlling the amount of the drug that is absorbed. Given these issues, this would lead to high and unnecessary costs for drugs already on the market, but may prove useful for new candidate drugs designed for this system.
Coated and dissolvable microneedles are among the newest types of solid microneedles. They deliver the drug directly into the targeted area of the skin as a dissolvable polymer matrix microneedle releases the drug it carries. Although these microneedles would allow for the delivery for a more precise dose of drug compared to that of the topical cream, coated and dissolvable microneedles still face important limitations. The amount of drug that can be contained in the dissolvable matrix of a microneedle device that is the size of a household adhesive bandage may be too low to treat a given condition or have the desired effect, and a patch with a fixed size means that the dosage is also fixed and cannot be customized by the administrator in the way that a conventional syringe can. While there may be utility in these systems, solid microneedles are not versatile enough for widespread use over many different drug classes.
Dissolving Microneedles Technology
In order to increase the safety of microneedles, biodegradable polymer microneedles have become another direction of microneedles development. Polymer microneedles were prepared by polylactic acid (PLA), polyglycolic acid (PGA) and their polymers (PLGA). Ultraviolet lithography, reactive ion etching and a new lens technology were used to prepare three kinds of microneedles with different shapes: beveled-tip, chisel-tip and Tapered-tip. The diameter, tip shape and needle spacing of microneedles can be adjusted by the shape and size of lithographic mask, and the length of microneedles can be adjusted by the parameters of reactive ion etching. Different shapes of needle tips help to reduce the resistance of micro-needles to penetrate the skin. The transdermal drug delivery experiments with calcein and bovine serum albumin showed that the transdermal absorption of the two drugs increased 100 times after 20 needle arrays were inserted and removed, and 1000 times after 100 needle arrays were inserted and removed. These results indicate that the polymer microneedle can significantly increase the transdermal absorption of drugs.
Polymer microneedles have good biocompatibility, biodegradability and low cost. With the emergence of new molecular materials, polymer microneedles will have good research and application prospects. However, compared with metal microneedles and silicon microneedles, the strength of the microneedles is poor, and the selection of materials and processing technology need to be improved.