Dissolving microneedles for transdermal drug delivery

Abstract

Microfabrication technology has been adapted to produce micron-scale needles as a safer and painless alternative to hypodermic needle injection, especially for protein biotherapeutics and vaccines. This study presents a design that encapsulates molecules within microneedles that dissolve within the skin for bolus or sustained delivery and leave behind no biohazardous sharp medical waste. A fabrication process was developed based on casting a viscous aqueous solution during centrifugation to fill a micro-fabricated mold with biocompatible carboxymethylcellulose or amylopectin formulations. This process encapsulated sulforhodamine B, bovine serum albumin, and lysozyme; lysozyme was shown to retain full enzymatic activity after encapsulation and to remain 96% active after storage for two months at room temperature. Microneedles were also shown to be strong enough to insert into cadaver skin and then to dissolve within minutes. Bolus delivery was achieved by encapsulating molecules just within microneedle shafts. For the first time, sustained delivery over hours to days was achieved by encapsulating molecules within the microneedle backing, which served as a controlled release reservoir that delivered molecules by a combination of swelling the backing with interstitial fluid drawn out of the skin and molecule diffusion into the skin via channels formed by dissolved microneedles. We conclude that dissolving microneedles can be designed to gently encapsulate molecules, insert into skin, and enable bolus or sustained release delivery.

Transdermal Protein Delivery Using Choline and Geranate (CAGE) Deep Eutectic Solvent

“…[42] Chen et al reported that BSA loaded chitosan microneedle patches led to sustained release of BSA for 8 d while Lee et al and Sullivan et al demonstrated that microneedles that "dissolve" in the skin could be used for transdermal delivery of BSA and lysozyme. [43][44][45] Prausnitz et al encapsulated influenza vaccine in dissolving microneedle patches made from polyvinylpyrrolidone and found that the vaccine was not only stable long-term but also was effectively delivered across the skin. The formulation exhibited superior immune response compared to the same dose via intramuscular injection.…”

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

“…This can be further enhanced when the interstitial fluid is absorbed and spreads through the polymer matrix during the dissolution process. 44 Given that all formulations in this study produced strong, sharp microneedles all 4 polymers displayed suitable characteristics for further in vitro analysis.…”

Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery

“…The backing layer of these needles was composed of a swellable hydrogel (CMC and amylopectin) loaded with sulforhodamine which allowed for a sustained release of up to 1mg over 72+ hours. 59 Donnelly et al produced hydrogel microneedles, which upon insertion absorb interstitial fluid in the skin and swell. The microneedles were created from crosslinked poly(methylvinylether/maelic acid) (PMVE/MA) 60 and poly(ethyleneglycol) (PEG) 43 or PMVE/MA crosslinked with glycerol 61 .…”