When it comes to 3D printing, the sky is the limit. As 3D printing technology continues to advance, applications can be as far reaching as airplane and automobile parts to medical devices and even anatomically correct, biocompatible models. Although 3D printing technology is developing at a rapid pace, the technology itself is not new. It emerged in the 1980s as a means of creating rapid prototypes. In recent years the applications for 3D printed models have evolved with the available hardware, software, and printable materials. Evolving technology, paired with the creative and innovative minds of scientists, engineers, and physicians, has been the launching pad for developments within 3D printing technology specific to healthcare. One way 3D printing technology is poised to create better patient outcomes is in creating an anatomically and patient-specific models to aid in surgery and medical procedures. With the capability to 3D ...
Are you afraid of needles? What if they’re so small they don’t penetrate your skin? And feel like a cat’s tongue?
That’s right, microneedles are really small — less than a millimeter long. They can be solid or hollow, and can be made of silicon, metal, or polymers, depending on the application. Microneedles (MNs) are typically organized into an array on a transdermal patch (with a density that can exceed 1,000 microneedles per cm2) for sustained delivery, on a roller for skin pretreatment to increase skin permeability, or on a flat delivery port attached to a syringe.
How do they work? An article in the Journal of Controlled Release provides a good explanation:
Microneedles are a minimally invasive means of increasing the permeability of the skin by piercing the stratum corneum and creating transient micropores through which a drug can passively diffuse. This novel delivery method allows for a wider variety of molecules to pass the skin’s barrier, thus allowing the advantages of transdermal delivery to be applied to a large range of clinical applications, including diabetes, severe osteoporosis, and influenza vaccination […] Treatment with MN arrays is relatively painless and generally well tolerated by most patients, making this a very realistic technique for clinical implementation.
The first report of micro fabricated microneedles used for transdermal drug delivery appeared in 1998. Since then, there have been more than 200 biomedical publications on microneedle transdermal delivery, with 46 research reports published this year. While hollow microneedles are used for drug infusion into the skin, polymer microneedles can encapsulate drugs and fully or partially dissolve in the skin. Since 2003, polymer microneedle arrays, including biodegradable ones, have been actively investigated.
The most promising polymer microneedles are those made of dissolvable, swellable, and biodegradable polymers. According to two recent polymer microneedle reviews, in PloS One and in Drug Design, Development and Therapy journals, dissolvable MNs are being used for rapid release of drugs (such as insulin) and vaccines, and are good for short-term applications. The dissolvable microneedles were made of maltose, carboxymethylcellulose, amylopectin, poly (methylvinylether/maleic anhydride), sodium hyaluronate, chondroitin sulphate/dextrin, sodium alginate, and hydroxypropyl cellulose.
Swellable microneedles are made of hydrogels. They create semipermanent micro channels and are used for prolonged delivery when integrated with a drug reservoir (a dermal patch). They may be used for bolus and pulsatile delivery if aided by an electrical source. In swellable MNs the delivery rate is controlled by the cross-link density of the hydrogel. Swellable MNs have been made of (PMVE/MA)-poly (ethylene glycol), PVA-dextran, polyvinyl alcohol (PVA), and gelatin hydrogels. The swelling of hydrogels due to contact with body fluids can be used to create intentional cracking of the microneedle tips, which remain in the skin for prolonged drug delivery.
Microneedles made of biodegradable polymers are used for slow, controlled release of active pharmaceutical ingredients, with the release sustainable for months. A single drug can be encapsulated within the needle, or double encapsulation can be used (a drug is first encapsulated within microparticles, and then the drug-loaded microparticles are encapsulated within needles). The use of poly(lactic-co-glycolic) acid (PLGA), polylactic acid, polyglycolic acid, polycarbonate, polystyrene, chitosan, and silk protein have been reported in the production of biodegradable microneedles.
A combination of several materials can result in microneedles with “smart” behavior. For example, separable arrowhead microneedles with micron-sized sharp polymer tips are mounted on blunt metal shafts. Once in the skin, the arrowheads (with an encapsulated drug) separate from the metal shafts and remain in the skin for subsequent drug release. The shafts are removed.
How are polymer microneedles made? Typically they are micro-molded in polydimethylsiloxane (PDMS), which is thermally stable, biologically and chemically compatible, safe, flexible, hydrophobic, non-hygroscopic, inert, and optically transparent. Master templates are used to manufacture PDMS micromolds, which are filled with polymer resins, loaded microcapsules, and/or hydrogels. The cast microneedles are then removed and dried. Vacuum deposition and centrifugation often are used in casting the microneedle matrix.
What can be delivered by microneedles? A variety of drugs and macromolecules has been tested for microneedle delivery. They include vaccines (including DNA vaccines), growth and thyroid hormones, insulin, analgesic and anti-inflammatory drugs, opioid antagonists, and immune stimulators. The majority of research has been done on animal models; however, human studies are advancing too. The first commercial MN product in the United States, an influenza vaccination for adults ages 18–64 (Fluzone Intradermal), was approved in 2011.
Commercialization of microneedle devices is in the early stage, although 3M Microneedle Technology (with divisions in the U.S.A., U.K., Japan, and Singapore) already offers hollow and solid microneedle systems for transdermal delivery of liquids, proteins, and vaccines. Hopefully, we will see them soon in doctors’ offices!
Comments
Post a Comment