Fabrication of Silk Microneedles for Controlled‐Release Drug Delivery

Abstract

Microneedles are emerging as a minimally invasive drug delivery alternative to hypodermic needles. Current material systems utilized in microneedles impose constraints hindering the further development of this technology. In particular, it is difficult to preserve sensitive biochemical compounds (such as pharmaceuticals) during processing in a single microneedle system and subsequently achieve their controlled release. A possible solution involves fabricating microneedles systems from the biomaterial silk fibroin. Silk fibroin combines excellent mechanical properties, biocompatibility, biodegradability, benign processing conditions, and the ability to preserve and maintain the activity of biological compounds entrained in its material matrix. The degradation rate of silk fibroin and the diffusion rate of the entrained molecules can be controlled simply by adjusting post‐processing conditions. This combination of properties makes silk an ideal choice to improve on existing issues associated with other microneedle‐based drug delivery system. In this study, a fabrication method to produce silk biopolymer microstructures with the high aspect ratios and mechanical properties required to manufacture microneedle systems is reported. Room temperature and aqueous‐based micromolding allows for the bulk loading of these microneedles with labile drugs. The drug release rate is decreased 5.6‐fold by adjusting the post‐processing conditions of the microneedles, mainly by controlling the silk protein secondary structure. The release kinetics are quantified in an in vitro collagen hydrogel model, which allows tracking of the model drug. Antibiotic loaded silk microneedles are manufactured and used to demonstrate a 10‐fold reduction of bacterial density after their application. The processing strategies developed in this study can be expanded to other silk‐based structural formats for drug delivery and biologicals storage applications.

Stabilization of vaccines and antibiotics in silk and eliminating the cold chain

“…When the stabilization data presented here are combined with the remarkable mechanical features and tunable release kinetics characteristic of silk carriers (30,43,44), a robust stabilization and delivery platform for antibiotics can be envisioned, extending even to microneedle formats (30). In total, these findings suggest a new path towards eliminating the cold chain, providing new venues towards improved processing, distribution and use of labile therapeutics such as antibiotics and vaccines.…”

“…We demonstrate remarkable stabilization of these labile compounds and also provide mechanistic insight. Because silk can be formed into any variety of material formats, including films, hydrogels, microspheres and microneedles (17,30), the proposed system has potential use ex vivo or in vivo as drug delivery vehicles. Further, the results provide a feasible path forward to revolutionize the cold chain and provide more efficient and widespread distribution of labile therapeutics throughout the world (Fig.…”

Development of silk fibroin-derived nanofibrous drug delivery system in supercritical CO2

“…Good biocompatibility, controllable biodegradation, complete resorbability, and excellent mechanical properties, make SF an ideal biomaterial [1][2][3]. Recently, SF has elicited considerable interests in drug delivery, especially in fiber/fibrous formulation [4,5] Traditional technologies used to fabricate SF fiber/fibrous structure comprises electrospinning and lyophilization [6][7][8]. However, organic solvent residue and extreme temperature remains to be concerned.…”

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).…”