Microneedles Integrated with ZnO Quantum-Dot-Capped Mesoporous Bioactive Glasses for Glucose-Mediated Insulin Delivery

A self-responsive insulin delivery system is highly desirable because of its high sensitivity dependent on blood glucose levels. Herein, a smart pH-triggered and glucose-mediated transdermal delivery system, insulin-loaded and ZnO quantum dots (ZnO QDs) capped mesoporous bioactive glasses (MBGs) integrated with microneedles (MNs), was developed to achieve control and painless administration. ZnO QDs as a promise pH-responsive switch were employed to cap the nanopores of MBGs via electrostatic interaction. The drug (insulin) and glucose-responsive factor (glucose oxidase/catalase, GO_<i>x</i>/CAT) were sealed into the pores of MBGs. GO_<i>x</i>/CAT in the MBGs could catalyze glucose to form gluconic acid, resulting decrease in the local pH. The ZnO QDs on the surface of the MBGs could be dissolved in the acidic condition, leading to disassembly of the pH-sensitive MBGs and then release of preloaded insulin from the MBGs. As a result of administration in a diabetic model, an excellent hypoglycemic effect and lower hypoglycemia risk were obtained. These results indicate that as-prepared pH-triggered and glucose-mediated transdermal delivery systems have hopeful applications in the treatment of diabetes

Corona Liquid Crystalline Order Helps to Form Single Crystals When Self-Assembly Takes Place in the Crystalline/Liquid Crystalline Block Copolymers

Crystalline/ionic liquid crystalline block copolymers (BCPs) with various compositions have been successfully prepared by sequential reactions. The effect of corona liquid crystalline order on self-assembly of BCPs in selective solvent is investigated in detail. It is found that two-dimensional single crystals with well-developed shapes are formed when the liquid crystalline order is present. By contrast, ill-developed platelets with small size or one-dimensional worm-like micelles are assembled if the liquid crystalline order of the corona segments is lost. It is speculated that the preferred parallel arrangement of liquid crystalline block enables it to expose more growth front of crystals. Accordingly, epitaxial crystallization will proceed readily, leading to fabrication of the well-defined single crystals

Separable Microneedles for Near-Infrared Light-Triggered Transdermal Delivery of Metformin in Diabetic Rats

Near-infrared (NIR) light-triggered and separable segmented microneedles (MNs), consisting of lauric acid and polycaprolactone (LA/PCL) arrowheads and poly­(vinyl alcohol) and polycaprolactone (PVA/PVP) supporting bases, have been fabricated. A hypoglycemic drug (metformin) and photothermal conversion factor (Cu₇S₄ nanoparticles) are encapsulated into LA/PCL arrowheads. Due to the dissolution of soluble supporting bases after the absorption of tissue fluid, the separable MNs arrowheads can be embedded into skin after insertion. Under the NIR-light irradiation, the LA/PCL arrowheads exhibit an excellent thermal-ablation change with a low amount of Cu₇S₄ nanoparticles (0.1 wt %) due to the low melting point of LA and PCL, thus enabling the release behavior of the encapsulated model drug to be photothermally triggered. Compared to the hypodermic injection of metformin, the thermal ablation of separable MNs triggered by NIR irradiation in the current research exhibit an excellent hypoglycemic effect in vivo. It suggests that the NIR-induced thermal-ablation MNs comprise a prospective transdermal drug-delivery system for the precise control of the timing and dosage of a drug that is dependent on NIR administration

Design and Synthesis of Fluorinated Amphiphile as ¹⁹F MRI/Fluorescence Dual-Imaging Agent by Tuning the Self-Assembly

Both ¹⁹F MRI and optical imaging are powerful noninvasive molecular imaging modalities in biomedical applications. To integrate these two complementary imaging modalities, the design and synthesis of a novel ¹⁹F MRI/fluorescence dual-modal imaging agent is reported herein. Through Sonogashira coupling reaction between the fluorinated phenylacetylene and 1,2,4,5-tetraiodobenzene, a fluorophore with 48 symmetrical fluorines at its periphery was constructed with high efficacy. High aqueous solubility was achieved by PEGylation of the fluorophore with monodisperse PEGs. However, an unexpected self-assembly of the PEGylated amphiphilic fluorophore in water “turned off” the ¹⁹F NMR signal. However, hydrogenation of the triple bonds or introduction of branched monodisperse PEGs was able to efficiently tune the self-assembly, resulting in the “turning on” of the ¹⁹F NMR signal. One of these amphiphiles combines the advantages of label-free fluorescence, high ¹⁹F MRI sensitivity, biocompatibility, and excellent aqueous solubility. The results demonstrate the great potential of such amphiphiles for real-time ¹⁹F MRI and fluorescence dual-modality imaging

Surfactant-Mediated Crystallization-Driven Self-Assembly of Crystalline/Ionic Complexed Block Copolymers in Aqueous Solution

A series of crystalline/ionic complexed block copolymers (BCPs) with various compositions have been prepared by sequential reactions. The BCPs with different hydrophilic fractions can self-assemble into various morphologies, such as spindlelike, rodlike, and spherical micelles with different crystallinity of the core. Bis­(2-ethylhexyl) sulfosuccinate sodium salt (AOT) is added as a surfactant to induce the morphological transition of BCPs in aqueous media. The introduced AOT can be tightly bound to the cationic units, and a water-insoluble unit in the corona forms, leading to a reduced tethering density. Consequently, morphological variety changing from rods to platelets to fibril to dendrite-like micelles can be observed