Dissolvable Microneedle Arrays for Intradermal Delivery of Biologics: Fabrication and Application

Abstract

Purpose Design and evaluate a new micro-machining based approach for fabricating dissolvable microneedle arrays (MNAs) with diverse geometries and from different materials for dry delivery to skin microenvironments. The aims are to describe the new fabrication method, to evaluate geometric and material capability as well as reproducibility of the method, and to demonstrate the effectiveness of fabricated MNAs in delivering bioactive molecules. Methods Precise master molds were created using micromilling. Micromolding was used to create elastomer production molds from master molds. The dissolvable MNAs were then fabricated using the spin-casting method. Fabricated MNAs with different geometries were evaluated for reproducibility. MNAs from different materials were fabricated to show material capability. MNAs with embedded bioactive components were tested for functionality on human and mice skin. Results MNAs with different geometries and from carboxymethyl cellulose, polyvinyl pyrrolidone and maltodextrin were created reproducibly using our method. MNAs successfully pierce the skin, precisely deliver their bioactive cargo to skin and induce specific immunity in mice. Conclusions We demonstrated that the new fabrication approach enables creating dissolvable MNAs with diverse geometries and from different materials reproducibly. We also demonstrated the application of MNAs for precise and specific delivery of biomolecules to skin microenvironments in vitro and in vivo.

Microneedles for drug delivery: trends and progress

“…They can be categorized into two types, solid or hollow MNs (Bariya et al, 2011). The materials that have been used to fabricate them range from metal (Choi et al, 2013), glass, silicon (Wei-Ze et al, 2010) and biodegradable polymers (polydimethylsiloxane) (Chu & Prausnitz, 2011;Bediz et al, 2013) and silk fibroin (Tsioris et al, 2012). More recently, the use of fish scales have also been investigated (Olatunji et al, 2014).…”

Novel Use of Pectin as a Microneedle Base

“…1h), where overall a spin-casting method was mainly used. 2,17,18) Scanning electron microscopy (SEM) analysis of pectin MNs, differential scanning calorimetry (DSC) analysis of pectin MNs, bovine serum albumin (BSA)/pectin MNs interaction studies with bicinchoninic acid (BCA) method, BSA/ pectin MNs were performed to the similar of our earlier publication. Fig.…”

“…4,5) Although the first silicon MNs were of being too brittle and possessing non-biocompatible nature, 6,7) intensive research since then has yielded many pharmaceutical, polymer-based MN systems as alternatives. 2,[8][9][10][11][12][13][14][15][16] Micro manufacturing techniques, 17,18) deduction of suitable polymers for MNs and optimization of the formulation parameters to produce MNs that possess characteristics like solubility, swelling, and biodegradability were previously published. 8) Polymeric MNs have great potential to start a million dollar market up by revolutionizing not only the drug delivery systems (conventional transdermal patches and hypodermic needles), but also drug monitoring devices (both bench top and portable systems).…”

Toward Biofunctional Microneedles for Stimulus Responsive Drug Delivery

“…Many microneedle systems (e.g. coated 41 , dissolvable 42 , swellable 43 ) incorporate the drug into the device in a solid-state, extending the shelf-life compared to drug solutions in syringes 44 . Post-insertion, these needles are no longer sharp 42,43 , thus preventing reuse, needle-stick injury as well as reducing waste management issues.…”

“…Bediz et al used corboxy-methyl-cellulose (CMC), poly(vinyl-pyrrolidone) (PVP) and maltodextrin (MD) in a variety of ratios and saw a delayed rate of release of ovalbumin with increased amounts of PVP. 42 Chu et al produced separable arrowhead microneedles, designed to disengage from the shaft within seconds of insertion. The drug-loaded arrowhead is left embedded in the epidermis and can degrade to a tuneable profile depending on the arrowhead formulation.…”