A Double‐Layered Microneedle Platform Fabricated through Frozen Spray‐Coating

Abstract

This work reports a frozen spray-coating method for the fabrication of double-layered microneedles (MNs). Taking swellable methacrylated hyaluronic acid (MeHA)-derived MNs as the model, both hydrophobic molecules (Nile red, Cy5) and hydrophilic ones (FITC, FITC-Dextran, Insulin) can be homogeneously coated without impacting the mechanical properties of the original MeHA MNs. The prepared double-layered MNs can execute multiple roles. It is demonstrated that insulin-coated MeHA double-layered MNs allow the effective delivery of the insulin into circulation of mice for controlling the blood glucose level while they also permit the extraction of skin interstitial fluid for the timely analysis of the biomarker (glucose).

Hydrogel-Based Technologies for the Diagnosis of Skin Pathology

“…Furthermore, PVA gel MNs facilitate on-demand insulin release following cleavage of labile linkers, based on nearby glucose concentration [16]. From our study, versatile post-assembly loading of hydrogel with hydrophobic and hydrophilic molecules was achieved through the swelling and freeze-spraying method, as an alternative to conventional incorporation preassembly [17,18]. With notable growth in the spectrum of functional mono/polymers and assembly strategies, the applicability of hydrogels is ever expanding as well.…”

“…Forming a highly swellable methacrylate hyaluronic acid (MeHA) gel MN, our group was able to isolate substantial (>1 μL) ISF within 1 min for subsequent centrifugation retrieval of metabolites and offline ELISA analysis ( Figure 5B). Shown for glucose and cholesterol, we obtained great correlation for either marker to the serum measurement [17,61]. Alternatively, enzymes-embedded hydrogels are coupled with electrodes or pH-sensitive fluorophores to directly report the presence of metabolites.…”

“…Employing the two above-mentioned crosslinking strategies, hydrogel sensors can be conveniently prepared by molding polymer substances together with sensing moieties into desirable morphology (e.g., patches and MNs) or by generating particle droplets through microfluidic technology [45,46]. Typically, hydrogel solution is poured into a metal or polydimethylsiloxane (PDMS)-based template mold, centrifuged to entirely fill the mold spacing (especially for viscous hydrogel solution filling small gaps like MN tips), and crosslinked (e.g., photoinitiator and UV irradiation) to allow hardening and subsequent removal of the gel structures from the mold [17,47]. Colorimetric, enzymatic, and/or electrochemical sensor moieties have been incorporated within hydrogel MNs in this fashion to facilitate the non-invasive assessment and monitoring of skin biomarkers without burdensome devices [48,49].…”

Microneedle-based bioassays

“…62 To improve the extraction and detection efficiencies, MNs with novel microstructures or materials can be prepared by a multi-step process. [63][64][65][66][67] For example, Mandal et al designed a MN patch with a core-shell structure for longitudinal sampling of cells and skin ISF. The group rst fabricated polylactic acid (PLA) MN arrays through PDMS molds and subsequently coated them with polylysine, alginate, and sucrose mixtures.…”

Effective Dispensing Methods for Loading Drugs Only to the Tip of DNA Microneedles

“…Moreover, Chen et al [ 24 ] proposed the fabrication of MNs using compressed droplets of magnetic rheological fluid under an external magnetic field to quickly fabricate MNs without a conventional mold and mask. Ning et al [ 25 ] developed a strategy of freeze spray coating, whereby a solution containing coating molecules was rapidly frozen in liquid nitrogen in advance to achieve uniform coating on the MNs, for a double-layer structure. These studies have demonstrated the improved fabrication of MNs and efficient performance for drug delivery.…”