Microneedles have emerged as a novel transdermal delivery tool that enables the delivery of various products such as drugs, vaccines, or cosmetic ingredients. Although the demand for solid microneedles composed of biocompatible polymer is increasing, the manufacture of microneedles using poly-lactic acid (PLA) with rapid drug-releasing is yet to be established and the process is still in its infancy. Here, we propose a novel strategy for the fabrication of PLA solid microneedles which enable a drug to be burst-released based on a solvent-casting process. This approach offers extreme simplicity, broad geometric capability, cost-effectiveness, and scalability based on high fidelity-replicas. It was verified that microneedles of various heights (250–500 μm) could be fabricated with appropriate mechanical strength to penetrate the stratum corneum layer of skin. By adding sugar in the composition of PLA microneedle, it was observed that both hydrophilic and hydrophobic drugs can be rapidly released within 30 min. Our burst drug-releasing PLA microneedle having both characteristics of solid microneedle and soluble microneedle and its fabrication approach based on solvent-casting will contribute to getting microneedle technology close to commercialization and beyond existing technical limitations.

Although dissolving microneedles have garnered considerable attention as transdermal delivery tools, insufficient drug loading remains a challenge owing to their small dimension. Herein, we report a one-step process of synthesizing semi-dissolving microneedle (SDMN) patches that enable effective transdermal drug delivery without loading drugs themselves by introducing TEMPO-oxidized bacterial cellulose nanofibers (TOBCNs), which are well dispersed, while retaining their unique properties in the aqueous phase. The SDMN patch fabricated by the micro-molding of a TOBCN/hydrophilic biopolymer mixture had a two-layer structure comprising a water-soluble needle layer and a TOBCN-containing insoluble backing layer. Moreover, the SDMN patch, which had a hole in the backing layer where TOBCNs are distributed uniformly, could offer novel advantages for the delivery of large quantities of active ingredients. In vitro permeation analysis confirmed that TOBCNs with high water absorption capacity could serve as drug reservoirs. Upon SDMN insertion and the application of drug aqueous solution through the drug inlet hole, the TOBCNs rapidly absorbed the solution and supplied it to the needle layer. Simultaneously, the needle layer dissolved in body fluids and the drug solution to form micro-channels, which enabled the delivery of larger quantities of drugs to the skin compared to that enabled by solution application alone.

Retinol has been widely used as an anti-wrinkle active ingredient in cosmetic fields. However, the oxidation of retinol by air was one of the critical problems for application in the skincare field. In this study, Retinol-loaded lipid nanocarriers were prepared via the vacuum emulsification method to increase the stability of retinol vulnerable to air and optimized encapsulation conditions and to increase the penetration efficiency into skin. Optimizing the components of lipid nanocarriers, gradients of carbon chain C8-22 using various lipid species which made the amorphous structure and enough spaces to load retinol inside the capsules were estimated from the lower enthalpy change and peak shift in DSC analysis. The vacuum-assisted lipid nanocarriers (VLN) could help suppress oxidation, which could have advantages to increase the thermal stability of retinol. The retinol-loaded VLN (VLN-ROL) had narrow size distribution under 0.3 PDI value, under 200 nm scaled particle size, and fully negative surface charge of about -50 mV for the electrostatic repulsion to avoid aggregation phenomenon among the lipid nanoparticles. It maintained 90% or more retinol concentration after 4 weeks of storage at 25, 40 and 50 °C and kept stable. The VLN-ROL-containing cream showed improved penetration efficiency applied to porcine skins compared to the commercial retinol 10S from BASF. The total amount of retinol into the skin of VLN-ROL (0.1% of retinol) was enhanced by about 2.2-fold (2.86 ± 0.23 μg) higher than that in 0.1% of bare retinol (about 1.29 ± 0.09 μg). In addition, applied on a 3D Human skin model, the epidermal thickness and the relative percentage of dermal collagen area effectively increased compared to the control and retinol, respectively. Additionally, the level of secreted IL-1α was lower and epidermal damage was weaker than commercial product A. This retinol-loaded lipid nanocarrier could be a potentially superior material for cosmetics and biomedical research.

We present a straightforward approach with high moldability for producing dual-responsive and multi-functional plasmonic hydrogel valves and biomimetic architectures that reversibly change volumes and colors in response to temperature and ion variations. Heating of a mixture of hybrid colloids (gold nanoparticles assembled on a hydrogel colloid) and hydrogel colloids rapidly induces (within 30 min) the formation of hydrogel architectures resembling mold shapes (cylinder, fish, butterfly). The biomimetic fish and butterfly display reversible changes in volumes and colors with variations of temperature and ionic conditions in aqueous solutions. The cylindrical plasmonic valves installed in flow tubes rapidly control water flow rate in on-off manner by responding to these stimuli. They also report these changes in terms of their colors. Therefore, the approach presented here might be helpful in developing new class of biomimetic and flow control systems where liquid conditions should be visually notified (e.g., glucose or ion concentration changes).

L-ascorbic acid (AA), a potent antioxidant, is commonly used topically in the pharmaceutical and cosmetic fields. However, the incorporation of AA into topical formulations is difficult because of its highly unstable nature and relatively poor skin permeability. In this study, we propose an alternative strategy for improving the solubility and topical delivery of AA through its conversion to a therapeutic deep eutectic system (THEDES). AA and betaine (Bet)-based THEDESs were prepared at certain molar ratios and characterized using polarized optical microscopy, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Solubility tests showed that AA in the form of THEDES was readily soluble in various polyols (glycerin, 1,3-butylene glycol, dipropylene glycol, and 1,3-propanediol) at a high concentration (approximately 40%). Furthermore, compared to AA alone or the physical mixture of AA and Bet, AA-based THEDES significantly enhanced AA delivery through porcine skin. In an in vivo human study, THEDES-containing serum reduced the markers of aging and induced an even skin tone. These findings indicate the utility of AA and Bet-based THEDES as novel transdermal delivery systems for AA. Furthermore, our approach also showed good extension to developing gluconolactone, a well-known natural antioxidant, and Bet-based THEDES, showing potential application in transdermal delivery systems.