MICRONEEDLES

Ashwini4NM12LVS06

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Bio-MEMS in Drug Delivery

• Conventional drug deliveryo Using pills/oral medication.o Injection- hypodermic needles and syringes.

• Drug concentration decreases gradually according to the body’s metabolism.

• Difficult to transport hydrophilic and high molecular weight drugs through stratum corneum layer of skin.

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MEMS for Drug delivery“MICRONEEDLES”

Microneedles are microfabricated devices for minimally invasive drug delivery applications.

Needles are designed to be as small as possible, extremely sharp, with submicron radii (typical upper end diameter: 5-40μm and effective length: 1000-2000μm).

Microneedles make micro-scale holes in the skin through which controlled drug delivery is possible.

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• Microneedles may be classified in two groups– Solid microneedles• Looks like acupuncture.• Coated with drug, so that once the device is pressed

into the skin, the drug simply dissolves off, being deposited in the dermis.

– Hollow microneedles• Has drug pathway inside the needle.• Can be attached to a syringe, enabling a solution of

drug to be injected through the microneedles.

• Apart from this there are also polymer microneedles that encapsulate drug and fully dissolve in the skin.

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• Existing microneedles are made using silicon, metal or biodegradable polymer materials.– Due to brittle nature of silicon, 5% of the microneedles

were observed to break and remain in the skin, leading to loss of drug as well as risk of toxicity or infection prevailed.

– Use of biodegradable polymer materials are hence gaining significance.

• Various materials such as hydrogel, maltose, drugs for treatment of skin diseases, cosmetic components, water-soluble materials and polymeric proteins are used to form biodegradable solid microneedles.

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Fabrication ofBiodegradable polymer Microneedles

• Master structures (from SU-8 epoxy photoresist or polyurethane) are made using lithography-based methods.

• Inverse molds (PDMS (polydimethyl siloxane) molds) of the master structures are then created.

• Replicates of the microneedles are prepared by melting biodegradable polymer formulations into the molds.

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• Two different geometries of Microneedles are fabricated– Beveled tip– Tapered cone

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Beveled-tip microneedles

• Master structures are created from SU-8 epoxy using UV lithography.

• SU-8 epoxy with photoinitiator is coated to a thickness of 300-350μm onto a silicon wafer and lithographically patterned into 100μm diameter cylinders.

• Cylinders are arranged in an array.– Center-to-center spacing between cylinders in each

row:1400μm and between each column: 400μm.– Array contains up to 20 cylinders in each row arranged in 6

columns for a total of 120 cylinders in an area of 9X9mm.

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• Space between cylinders is filled with a sacrificial polymer .

• Copper mask is patterned to asymmetrically cover the tops of epoxy cylinders and some of the sacrificial polymer on one side of each cylinder.

• Reactive ion etching partially removes uncovered sacrificial layer and asymmetrically etches the tips of the adjacent epoxy cylinders.

• Remaining sacrificial layer is removed by ethyl acetate.• Array of asymmetrically beveled tips obtained is coated

with poly(dimethylsiloxane) which is subsequently peeled off to make an inverse PDMS mold.

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Tapered-cone microneedles

• Microlens-based fabrication technique.• Chromium layer is deposited and patterned on a

glass substrate to form an array of circular dots of exposed glass.

• Isotropic wet etching of the exposed glass is performed to create concave wells, which are filled with SU-8 epoxy cast on the surface.

• The refractive index mismatch between SU-8 epoxy and glass creates an array of integrated microlenses.

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• Soft baking is followed by exposing the SU-8 film to the UV light from the bottom.

• Latent images are formed in the SU-8 epoxy as ray traces from the microlens structures.

• Development of Su-8 epoxy to obtain tapered-cone microneedle master structure.

• Inverse PDMS mold is made.

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Microneedles encapsulating drug

• A suspension of drug particles is filled into a microneedle mold.

• Evaporation of the solvent leaves solid drug particles partially filling the mold.

• Pellets of biodegradable polymer are melted into the mold under vacuum.

• Cooling and solidification of the polymer yields biodegradable polymer needles with encapsulated drug particles.

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Potentials of microneedle technology

• Microneedles have been proved useful for immunization programs and for mass vaccination.

• Membrane-impermeable molecules like proteins, DNA, peptides, oligonucleotides etc can be delivered into the body using microneedles.

• Very small microneedles provide highly targeted drug administration to individual cells.

• Thousands of needles are fabricated on a single wafer, leading to high accuracy, good reproducibility and moderate fabrication cost.

• They are capable of providing very accurate dosing, complex release patterns and biological drug stability by storing in micro volumes that can be precisely controlled.

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References

• Jung-Hwan Park, Mark G. Allen, Mark R. Prausnitz, “Polymer Microneedles for Controlled-Release Drug Delivery”, Pharmaceutical Research, Vol.23, No. 5, May 2006.

• Jung-Hwan Park, Mark G. Allen, Mark R. Prausnitz, “Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery”, Journal of Controlled Release 104 (2005) 51–66.

• Nahid Tabassum, Aasim Sofi and Tahir Khuroo, “Microneedle Technology: A New Drug Delivery System”, International Journal of Research in Pharmaceutical and Biomedical Sciences.

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