Oral formulations for highly lipophilic drugs: Impact of surface decoration on the efficacy of self-emulsifying drug delivery systems.

AIM: To evaluate the impact of the surface decoration of cannabidiol (CBD) loaded self-emulsifying drug delivery systems (SEDDS) on the efficacy of the formulations to cross the various barriers faced by orally administered drugs. METHODS: Polyethylene glycol (PEG)-free polyglycerol (PG)-based SEDDS, mixed zwitterionic phosphatidyl choline (PC)/PEG-containing SEDDS and PEG-based SEDDS were compared regarding stability against lipid degrading enzymes, surface properties, permeation across porcine mucus, cellular uptake and cytocompatibility. RESULTS: SEDDS with a size of about 200 nm with narrow size distributions were developed and loaded with 20-21 % of CBD. For PG containing PEG-free SEDDS increased degradation by lipid degrading enzymes was observed compared to PEG-containing formulations. The surface hydrophobicity of placebo SEDDS increased in the order of PG-based to mixed PC/PEG-based to PEG-based SEDDS. The influence of this surface hydrophobicity was also observed on the ability of the SEDDS to cross the mucus gel layer where highest mucus permeation was achieved for most hydrophobic PEG-based SEDDS. Highest cellular internalization was observed for PEG-based Lumogen Yellow (LY) loaded SEDDS with 92 % in Caco-2 cells compared to only 30 % for mixed PC/PEG-based SEDDS and 1 % for PG-based SEDDS, leading to a 100-fold improvement in cellular uptake for SEDDS having highest surface hydrophobicity. For cytocompatibility all developed placebo SEDDS showed similar results with a cell survival of above 75 % for concentrations below 0.05 % on Caco-2 cells. CONCLUSION: Higher surface hydrophobicity of SEDDS to orally deliver lipophilic drugs as CBD seems to be a promising approach to increase the intracellular drug concentration by an enhanced permeation through the mucus layer and cellular internalization.

Living Cell-Mediated Catalyst-Free Spontaneous Polymerization of Zwitterionic Methacrylates for Preparation of Probiotic-Loaded Hydrogels.

Living cell-mediated polymerization offers promising applications in biomaterials, yet its further biological utilization is hindered by the need for metal ions or radical initiators with available methods. In this study, we introduce a living cell-mediated polymerization that leverages the intrinsic metabolic activities of living cells to initiate and sustain free radical polymerization of zwitterionic methacrylates. The polymerization proceeded in the absence of transition metal catalysts, radical initiators, or light sources. The conversion of zwitterionic methacrylate strongly correlated with cellular activities and achieved a maximum conversion of 98% within 48 hours. Living cells efflux redox power across membranes through metabolism and that terminal electron fluxes are captured by zwitterionic methacrylates pre-assembled on the living cell surface to initiate radical polymerization reactions. The polymerization caused significant changes to the cell membrane surface and synthesized hydrogels with tailored mechanical properties. The polymer hydrogel obtained via probiotic E. coli Nissle 1917 was able to release the in-situ encapsulated molecules, which demonstrated living cell-mediated polymer hydrogel as a vehicle for the delivery of both cellular and molecular therapeutic agents. This research offered a green and efficient method for synthesizing bioactive materials and advancing the field of cellular therapeutics and drug delivery.

Ultrastable and Redispersible Zwitterionic Bottlebrush Micelles for Drug Delivery.

Bottlebrush copolymers are increasingly used for drug delivery and biological imaging applications in part due to the enhanced thermodynamic stability of their self-assemblies. Herein, we discuss the effect of hydrophilic block chemistry on the stability of bottlebrush micelles. Amphiphilic bottlebrushes with zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and nonionic polyethylene glycol (PEG) hydrophilic blocks were synthesized by "grafting from" polymerization and self-assembled into well-defined spherical micelles. Colloidal stability and stability against disassembly were challenged under high concentrations of NaCl, MgSO4, sodium dodecyl sulfate, fetal bovine serum, and elevated temperature. While both types of micelles appeared to be stable in many of these conditions, those with a PMPC shell consistently surpassed their PEG analogs. Moreover, when repeatedly subjected to lyophilization/resuspension cycles, PMPC micelles redispersed with no apparent variation in size or dispersity even in the absence of a cryoprotectant; PEG micelles readily aggregated. The observed excellent stability of PMPC micelles is attributed to the low critical micelle concentration of the bottlebrushes as well as to the strong hydration shell caused by ionic solvation of the phosphorylcholine moieties. Zwitterionic micelles were loaded with doxorubicin, and higher loading capacity/efficiency, as well as delayed release, was observed with increasing side-chain length. Finally, hemocompatibility studies of PMPC micelles demonstrated no disruption to the red blood cell membranes. The growing concern regarding the immunogenicity of PEG-based systems propels the search for alternative hydrophilic polymers; in this respect and for their outstanding stability, zwitterionic bottlebrush micelles represent excellent candidates for drug delivery and bioimaging applications.

Bactericidal and Antifouling Coatings with the "Killing-Repelling-Killing" Triple Function Based on Cationic Copolymers with Structure Conversion and Capsaicin Analogue Release.

The capsaicin analogue N-(4-hydroxy-3-methoxybenzyl) acrylamide (HMBA) was linked with polylauryl methacrylate-b-poly(2-(N,N-dimethylamino)ethyl methacrylate) (PLMA-b-PDMAEMA) via a quaternization reaction with 4-(acrylamidomethyl)-2-methoxyphenyl 2-chloroacetate (AAMPCA). The amphiphilic copolymers were capable of transforming its structure in response to the solvent change from aprotic to protic, which was verified by the 1H NMR spectrum. The resulting cationic copolymers underwent a hydrolysis process in water, yielding zwitterionic groups on surfaces. Meanwhile, the bactericidal reagent HMBA was released. It was proved that the hydrolysis rate of the copolymers accelerated with higher temperature, higher pH value, and higher hydrophilic block units. And the controllable, sustainable release of HMBA was achieved with copolymer-mediated hydrolysis. Protein-repellent and bactericidal tests on the surface of the coating proved that antifouling and bactericidal performances of the coating correlated to the structure conversion abilities of the corresponding copolymer. The dynamic monitoring of Escherichia coli adhesion in 3 h evidenced the antifouling and bactericidal process of copolymers with different block ratios and concentrations. The coating incorporated with 3% PLMA120-b-(PDMAEMA-AAMPCA)120 in polylactic acid base materials showed an adhesion ratio of E. coli less than 1% within 1 h, and the survival ratio of the adhered bacteria is <1%, suggesting its rapid speed and high efficiency in "bacterial repelling and killing". Also, the PLMA120-b-(PDMAEMA-AAMPCA)120 copolymer demonstrated enhanced bactericidal ability compared with the mixture of cationic poly(laruyl methacrylate)120-b-poly(carboxybetaine methacrylate ester)120 (PLMA120-b-PCBMAE120) and free HMBA. The lowest minimal inhibitory concentration was 0.078 mg/mL against Staphylococcus aureus and 0.312 mg/mL against E. coli, respectively.

An Exceptionally Salt Tolerant Copoly(Maleimide Sulfobetaine) - Structural Requirements for Ultra-Salt Tolerance.

Zwitterionic polymers are an important class of polymers with far-ranging applications. In the widely studied poly(meth)acrylate and poly(meth) acrylamide-based zwitterions, properties can be tuned by changing the nature of substituents attached to ammonium ions. However, these changes influenced salt tolerance of zwitterionic polymers only to a limited extent. Upon adding salt these polymers expanded in solution initially. Further increase in salt concentration caused the polymer chains to shrink similar to the common water soluble, uncharged polymers thereby deteriorating the viscosity of aqueous solutions. In contrast to the conventional poly(meth)acrylate and poly(meth)acrylamide-based zwitterions, zwitterionic copolymaleimides showed substituent dependent salt-tolerant nature. In the absence of any substituent on the polymer backbone such as zwitterionic poly(ethylene-alt-maleimide) (ZI-PEMA) the viscosity of salt solutions increased both with the increasing salt concentration as well as the concentration of polymer. This is likely due to the continuous expansion of polymer coil in salt solutions with increasing salt concentration caused primarily by the rigidity of the polymer backbone. ZI-PEMA also enhanced the saturation limit of mono- and divalent salts like sodium chloride and hydrated calcium bromide in water. This property is useful for various applications like fish curing, for making high-density fluids, refrigeration, etc. across various industrial sectors.

Mechanical Force on Hydrogel Implication on Enhanced Drug Release, Antibacterial, and M2 Macrophage Polarization: New Insights Alleviate Diabetic Wound Healing.

Diabetic foot ulcers/chronic wounds are difficult to treat because of dysfunctional macrophage response and decreased phenotype transition from the M1 to M2 status. This causes severe inflammation, less angiogenesis, microbial infections, and small deformation in wound beds, affecting the healing process. The commercial wound dressing material has limited efficacy, poor mechanical strength, extra pain, and new granulated tissue formed in a mesh of gauze. It is desired to create tough, skin-adhesive, antifouling, sustainable M2 phenotype-enabling, and mechanoresponsive drug-releasing hydrogel. To resolve this, zwitterionic poly(sulfobetaine methacrylate) (SB) incorporated with keratin-exfoliated MoS2 and bee-wax nanoparticles were developed to deliver phenytoin upon application of mechanical forces. Human hair keratin was used for exfoliation of MoS2, and bee-wax nanoparticles loaded with phenytoin were used as cross-linkers of SB hydrogel. The cross-linked SB-MO15-B hydrogel has high mechanical properties, with more tensile strength and strain of 118 kPa and 1485%. Under external mechanical force, hydrogel deformed to release phenytoin of 38% (tensile) and 24% (compressive), which was higher compared to static condition (12%). The penetration of phenytoin into skin tissue was also improved by the mechanical force applied to the hydrogel. SB-MO15-B hydrogel effectively activates the polarization of macrophages toward the M2 phenotype, promotes cell proliferation, and also shows superior antibacterial properties. In vivo results demonstrate that hydrogel rapidly promotes diabetic wound repair through fast antiinflammation and M2 macrophage polarization. Therefore, a robust mechanoresponsive hydrogel would provide a new strategy to deliver the drug and also tune the M2 macrophage polarization for chronic wound healing.

Dipole Moment Dictates the Preferential Immobilization in Gel Electrolytes for Ah-level Aqueous Zinc-Metal Batteries.

Aqueous Zn-metal batteries are of great interest due to their high material abundance, low production cost, and excellent safety. However, they suffer from severe side reactions and notorious dendrite growth closely related to electrolytes. Here, in-situ generated zwitterionic polymers are used as gel electrolytes to overcome these problems. It is shown that anions and H2O, but not anions and cations, are preferentially immobilized at different sites of zwitterionic polymers, facilitating the free migration of Zn2+ and reducing the side reactions. This immobilization can be associated with the dipole moment of zwitterionic polymers. As a result, poly[3-dimethyl(methacryloyl oxyethyl) ammonium propane sulfonate] (PDMAPS) stands out from a series of zwitterionic polymers and outperforms the other candidates in electrochemical performance. The symmetric cells using PDMAPS smoothly operate ~9000 h at 0.5 mA cm-2 for 0.5 mAh cm-2, much better than the controls. Moreover, PDMAPS enables an Ah-level pouch cell for continuous cycling. These results not only benefit the rational molecular design of advanced electrolytes, but also demonstrate the promising potential of zwitterionic polymers in aqueous Zn-metal batteries.

Croconic Acid Integrated Zwitterionic Conjugated Porous Polymer for Effective Iodine Adsorption.

Given the rapid growth of the nuclear sector, effective treatment of radioactive iodine is critical. Herein, we report the synthesis and the iodine adsorption properties of croconic acid (CTPB) and squaric acid (STPB) containing π-conjugated novel zwitterionic conjugated porous polymers (CPPs). The CPPs have been synthesized through a condensation reaction of tris(4-aminophenyl)benzene with croconic acid or squaric acid in high yields (~95%). The ionic nature of the polymers promoted high iodine/polyiodide vapour adsorption capacity of up to 4.6 g/g for CTPB and 3.5 g/g for STPB under ambient pressure at 80 °C. The zwitterionic framework (croconic acid or squaric acid units) coupled with the aromatic units is expected to effectively capture molecular iodine (I2) and polyiodides (I3- and I5-). The iodine adsorption properties of the polymers have been studied using Fourier-Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Brauner-Emmett-Teller (BET) analysis, and Raman Spectroscopy. Besides this work, there are only three ionic units for effective iodine adsorption. This work demonstrates the importance of zwitterionic units in the porous network reported for iodine adsorption and separation.

Peptide retention time prediction for hydrophilic interaction liquid chromatography at acidic pH in formic-acid based eluents.

Peptide separation selectivity was evaluated for hydrophilic interaction liquid chromatography (HILIC) ZIC-HILIC, ZIC-cHILIC, and XBridge Amide sorbents using formic acid as eluent additive (pH 2.7). Sequence-specific retention prediction algorithms were trained using retention datasets of ∼30,000 peptides for each column. Our retention models were able to attain ∼0.98 R2-value and yielded retention coefficients that can be probed to understand peptide-stationary phase interaction. Overall, the hydrophilicity for these columns decreased when the mobile phase changed pH from 4.5 to 2.7, when using 0.1 % formic acid in the mobile phase. The acidic residues became protonated, and the resultant hydrophilic interaction is dampened at the lower pH, leaving only the basic residues as the primary hydrophilic interactors. Hence, peptides of increasing charge have higher retention. In this comparison between the three columns, ZIC-HILIC has the highest chromatographic resolution between groups of peptides of different charge. From the position-dependent retention coefficients for ZIC-HILIC at pH 2.7, we found that the amino acids at the terminal positions of the peptide modulate the basicity of the N-terminal amino group or the C-terminal Arg/Lys for tryptic peptides. With respect to the separation orthogonality between HILIC and acidic pH RPLC for two dimensional separations, the orthogonality values were lower at pH 2.7 than operating HILIC at pH 4.5 for the first dimension. We also demonstrate that ZIC-HILIC was able to distinguish citrullinated and deamidated peptides based on predicted retention values.

Preparation and evaluation of a pyridine sulfonate betaine-based zwitterionic stationary phase for hydrophilic interaction chromatography.

A zwitterionic stationary phase comprising pyridinium cations and sulfonate anions was successfully developed through thiol-ene click chemistry. Using seven polar small molecules as probes, the zwitterionic stationary phase showed high separation selectivity and excellent column efficiency (35,200-54,800 plates/m) compared with two commercial columns. The influence of water proportion, salt concentration, and pH in the mobile phase, and column temperature, on the retention of six polar compounds was examined. The retention mechanism was explored by three hydrophilic retention models, Tanaka test and linear solvation energy relationship analysis. For the analysis of sample dairy products (milk powder, milk, and yogurt), the stationary phase was operated in hydrophilic interaction chromatography mode without the addition of buffer salts, facilitating rapid and efficient detection and quantification of melamine. The LOD and LOQ are 0.04 mg⋅g-1 and 0.13 mg⋅g-1, respectively, and the recovery rate is 90.3 - 102.8 %. The zwitterionic stationary phase has the advantages of simple preparation, good method reproducibility, good selectivity and high precision.

A Universal Zwitterionic Cross-Linking Strategy for Designing Conductive Soft Electronics with Enhanced Mechanical Properties.

Ionogels are emerging as promising electronics due to their exceptional ionic conductivity, stretchability, and high thermal stability. However, developing ionogels with enhanced mechanical properties without compromising conductivity and ion transport rates remains a significant challenge. Here, we report a zwitterionic cross-linker, 4-(2-(((2-(methacryloyloxy)ethyl)carbamoyl)oxy)ethyl)-4,14-dimethyl-8,13-dioxo-7,12-dioxa-4,9-diazapentadec-14-en-4-ium-1-propanesulfonate (MEPS) and utilized it to cross-link a variety of functional monomers, leading to the synthesis of conductive ionogels that exhibit both high mechanical strength and versatile applicability. Due to its abundant hydrogen bond donors/acceptors and zwitterionic moiety, MEPS exhibits several hundred times higher solubility in ionic liquids compared to conventional cross-linkers. As a proof-of-concept, the poly(acrylic acid-MEPS) ionogels demonstrate enhanced elongation, fracture toughness, and superior thermal stability, all while maintaining high conductivity due to the high affinity between ionic liquids and zwitterionic networks. Furthermore, MEPS-cross-linked poly(α-thioctic acid) electronics can be engineered as strain sensors, showing exceptional antifatigue properties and recyclability, remaining stable and functional over 300 consecutive cycles. This universal cross-linking strategy not only improves the overall performance of ionogels but also contributes to the development of next-generation soft electronics with enhanced functionality and durability.

Self-Polymerized Tough and High-Entanglement Zwitterionic Functional Hydrogels.

Zwitterionic hydrogels exhibit great potential in biomedical applications due to their antifouling properties and biocompatibility. However, the single-network structure of pure zwitterionic hydrogels leads to a low toughness and strength, limiting their application in biomedical fields. In this work, a high entanglement sulfobetaine methacrylate-dopamine hydrogel (SBMA-DA-PE) with low cross-linker content and high monomer concentration is prepared by using a dopamine oxidative radical polymerization method. Compared to a regular zwitterionic hydrogel, the SBMA-DA-PE hydrogel exhibits a 5-fold increase in tensile fracture stress and a 10-fold increase in compressive fracture stress. The SBMA-DA-PE hydrogel possesses excellent mechanical properties (the maximum compressive stress ≥4.85 MPa, the maximum compressive strain ≥90%). Besides, the non-covalent interactions between catechol or ortho-quinones within the SBMA-DA-PE hydrogel, combined with strong intermolecular electrostatic interactions, endow the SBMA-DA-PE hydrogel with great self-healing capabilities and fatigue resistance. The SBMA-DA-PE hydrogel demonstrates low swellability and possesses good antifouling properties. Furthermore, the good printability and conductivity of the tough SBMA-DA-PE hydrogel endows it with new possibilities for developing biological 3D scaffolds and electronic devices. Overall, this work provides new insights into the preparation of zwitterionic hydrogels with high mechanical strength and multi-functionality for biomedical applications.

A Polymer-Based Polar Stationary Phase Grafted With Modified Lysine for Hydrophilic Interaction Chromatography.

The high hydrophobicity and chemical inertness of poly(styrene-divinylbenzene) (PS-DVB) microspheres make their surface hydrophilic modification difficult. Here we describe a facile way to convert PS-DVB microspheres to hydrophilic, then can be used as polar stationary phase for hydrophilic interaction chromatography. This approach utilizes the grafting of an acrylamide-terminated lysine zwitterionic monomer onto PS-DVB microspheres via free radical polymerization. The obtained stationary phase shows good hydrophilicity and a typical retention mechanism of hydrophilic interaction chromatography toward several model polar analytes. It also exhibits obvious zwitterionic properties and is capable of separating cationic and anionic analytes simultaneously. The column shows negligible bleeding level, much superior to silica-based ones.

Influence of zwitterionic amphiphilic copolymers on heterogeneous gypsum formation: A promising approach for scaling resistance.

This study aims to investigate the influence of zwitterionic amphiphilic copolymers (ZACs) in the nucleation and growth of heterogeneous CaSO4 at the zwitterion-water interface, which is crucial for the prevention of mineral scaling and consequent downtime or suboptimal performance in industries like membrane desalination, heat exchangers, and pipeline transportation. In situ grazing incidence small angle X-ray Scattering (GISAXS), and quartz crystal microbalance with dissipation (QCM-D) techniques were used to analyze the evolution of CaSO4 particles on two new ZAC coatings: poly-(trifluoroethyl methacrylate-random-sulfobetaine methacrylate) (PTFEMA-r-SBMA, or PT:SBMA) and poly(trifluoroethyl methacrylate-random-2-methacryloyloxyethyl phosphorylcholine) (PTFEMA-r-MPC, or PT:MPC). The results showed that PT:MPC coatings promoted nucleation but inhibited crystal growth, resulting in slower overall reaction kinetics on PT:MPC coatings compared to PT:SBMA coatings. Interfacial interactions involving the substrates, sulfate minerals, and ions were examined, revealing that calcium ion adsorption, primarily governed by electrostatic attraction, played a crucial role in the nucleation and growth processes on both ZAC coatings. The crystal characterization revealed a phase transition from bassanite to gypsum on both ZAC coatings, suggesting that these zwitterionic materials can influence the mineral phase of heterogeneously formed CaSO4 crystals. These findings enhance our understanding of the fundamental mechanisms underlying heterogeneous CaSO4 scaling in the presence of zwitterionic materials.

Biodegradable Zwitterionic Polymers as PEG Alternatives for Drug Delivery.

Poly(ethylene glycol) (PEG) is a highly biocompatible and water-soluble polymer that is widely utilized for biomedical applications. Unfortunately, the immunogenicity and antigenicity of PEG severely restrict the biomedical efficacy of pegylated therapeutics. As emerging PEG alternatives, biodegradable zwitterionic polymers (ZPs) have attracted significant interest in recent years. Biodegradable ZPs generally are not only water-soluble and immunologically inert, but also possess a range of favorable biomedically relevant properties, without causing long-term side effects for in vivo biomedical applications. This review presents a systematic overview of recent studies on biodegradable ZPs. Their structural designs and synthetic strategies by integrating biodegradable base polymers with zwitterions are addressed. Their applications in the delivery of small molecule drugs (as mono-drugs or multi-drugs) and proteins are highlighted.

Copper and nitrogen-doped carbon quantum dots as green nano-probes for fluorimetric determination of delafloxacin; characterization and applications.

BACKGROUND: Carbon quantum dots (CQDs) have gained much interest recently for being efficient probes. Their cost-effectiveness, eco-friendliness, and unique photocatalytic activities made them distinctive alternatives to other luminescent approaches like fluorescent dyes and luminous derivatization. Meanwhile, delafloxacin (DLF) is a recently approved antibacterial medicine. DLF has been authorized for the treatment of soft-tissue and skin infections as well as pneumonia. Therefore, new eco-friendly, cost-effective, and sensitive tools are needed its estimation in different matrices. RESULTS: In the proposed study, green copper and nitrogen carbon dots (Cu-N@CDs) were synthesized from a green source (plum juice with copper sulphate). Cu-N@CQDs were then characterized using multiple tools including X-ray photon spectroscopy (XPS), FTIR and UV-VIS spectroscopy, Zeta potential measurements, High-resolution transmission electron microscopy (HRTEM), and fluorescence spectroscopy. After gradually adding DLF, the developed quantum dots' fluorescence was significantly enhanced within the working range of 0.5-100.0 ng mL-1. The limits of detection and quantification were 0.08 and 0.27 ng mL-1, respectively. The accuracy of the proposed method ranged from 96.00 to 99.12 % in recovery%, when recovered from milk and plasma samples. SIGNIFICANCE: Cu-N@CDs were utilized and validated for selectively determining DLF in several matrices including pharmaceutical forms, human plasma and in milk samples using spectrofluorimetric technique. The bio-analytical method is simple and could be used in content uniformity testing as well as in therapeutic drug monitoring in human plasma.

Synthesis, Surface Activity, Emulsifiability and Bactericidal Performance of Zwitterionic Tetrameric Surfactants.

In this paper, a series of tetrameric surfactants (4CnSAZs, n = 12, 14, 16) endowed with zwitterionic characteristic were synthesized by a simple and convenient method and their structures were characterized by FT-IR, 1H NMR and elemental analysis. Their physicochemical properties were studied using the Wilhelmy plate method, fluorescence spectra and dynamic light scattering technique. 4CnSAZs have higher surface activities and tend to adsorb at the air/water surface rather than self-assembling in aqueous solution. The thermodynamic parameters obtained from surface tension measurements show that both processes of adsorption and micellization of 4CnSAZs are spontaneous and that the micellization processes of 4CnSAZs are entropy-driven processes. Both adsorption and micellization of 4CnSAZs are inclined to occur with the increase of alkyl chain length or temperature. For 4C12SAZs, there are only small-size aggregates (micelles), while the large aggregates (vesicles) are observed at the alkyl length of 4CnSAZs of 14 or 16. This shows that the alkyl chain length for oligomeric surfactants has a greater sensitivity for aggregate growth. The aggregate morphologies obtained from the calculated values of critical packing parameter (p) for 4C14SAZs and 4C16SAZs can be supported by the DLS measurement results. The test results obtained by the separation-water-time method show that 4CnSAZs have good emulsification performance and that the prepared emulsions appear to exit in the form of multiple emulsions. In addition, 4CnSAZs have good antibacterial activities against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The present study reveals the unique behavior of a zwitterionic tetrameric surfactant and may give new insights into molecular design and synthesis of a high degree of surfactants with different structure characteristics for potential application in various industrial fields.

Synthesis of Novel Planar-Chiral Charge-Compensated nido-Carborane-Based Amino Acid.

Amino acids with unusual types of chirality and their derivatives have recently attracted attention as precursors in the synthesis of chiral catalysts and peptide analogues with unique properties. In this study, we have synthesized a new nido-carborane-based planar-chiral amino acid, in the molecule of which the amino group is directly bonded to the B(3) atom, and the carboxyl group is attached to the B(9) atom through the CH2S+(Me) fragment. 3-Amino-9-dimethylsulfonio-nido-carborane, prepared in three steps from 3-amino-closo-carborane in a high yield, was a key intermediate in the synthesis of the target planar-chiral amino acid. The carboxymethyl group at the sulfur atom was introduced by the demethylation reaction of the dimethylsulfonio derivative, followed by S-alkylation. The structure of new 3,9-disubstituted nido-carboranes was studied for the first time using NMR spectroscopy. The resonances of all boron atoms in the 11B NMR spectrum of 3-amino-9-dimethylsulfonio-nido-carborane were assigned based on the 2D NMR correlation experiments. The nido-carborane-based planar-chiral amino acid and related compounds are of interest as a basis for peptide-like compounds and chiral ligands.

Biocompatible Core-Shell Microneedle Sensor Filled with Zwitterionic Polymer Hydrogel for Rapid Continuous Transdermal Monitoring.

Microneedle (MN)-based electrochemical biosensors hold promising potential for noninvasive continuous monitoring of interstitial fluid biomarkers. However, challenges, such as instability and biofouling, exist. This study proposes a design employing hollow MN to encapsulate a zwitterionic polymer hydrogel sensing layer with excellent biocompatibility and antifouling properties to address these issues. MN shell isolates the internal microporous sensing layer from subcutaneous friction, and the hydrogel filling leverages the MNs' three-dimensional structures, enabling high-dense loading of biorecognition elements. The hollow MNs are successfully fabricated from high-molecular-weight polylactic acid via drawing lithography, exhibiting sufficient strength for effective epidermis penetration. Additionally, a high-performance gold nanoconductive layer is successfully deposited inside the MN hollow channel, establishing a stable electrical connection between the polymer MN and the hydrogel sensing layer. To support the design, numerical simulations of position-based diffusive analyte solutes reveal fast-responsive electrochemical signals attributed to the high diffusion coefficient of the hydrogel and the concentrated structure of the hollow channel encapsulation. Experimental results and numerical simulations underscore the advantages of this design, showcasing rapid response, high sensitivity, long-term stability, and excellent antifouling properties. Fabricated MN sensors exhibited biosafety, feasibility, and effectiveness, with accurate and rapid in vivo glucose monitoring ability. This study emphasizes the significance of rational design, structural utilization, and micro-nanofabrication to unlock the untapped potential of MN biosensors.

Bioinspired Asymmetric-Adhesion Janus Hydrogel Patch Regulating by Zwitterionic Polymers for Wet Tissues Adhesion and Postoperative Adhesion Prevention.

Asymmetrically adhesive hydrogel patch with robust wet tissue adhesion simultaneously anti-postoperative adhesion is essential for clinical applications in internal soft-tissue repair and postoperative anti-adhesion. Herein, inspired by the lubricative role of serosa and the underwater adhesion mechanism of mussels, an asymmetrically adhesive hydrogel Janus patch is developed with adhesion layer (AL) and anti-adhesion layer (anti-AL) through an in situ step-by-step polymerization process in the mold. The AL exhibits excellent adhesion to internal soft-tissues. In contrast, the anti-AL demonstrated ultralow fouling property against protein and fibroblasts, which hinders the early and advanced stages of development of the adhesion. Moreover, the Janus patch simultaneously promotes tissue regeneration via ROS clearance capability of catechol moieties in the AL. Results from in vivo experiments with rabbits and rats demonstrate that the AL strongly adheres to traumatized tissue, while the anti-AL surface demonstrate efficacy in preventing of post-abdominal surgery adhesions in contrast to clinical patches. Considering the advantages in terms of therapeutic efficacy and off the shelf, the Janus patch developed in this work presents a promise for preventing postoperative adhesions and promoting regeneration of internal tissue defects.