A bio-ionic liquid based self-healable and adhesive ionic hydrogel for the on-demand transdermal delivery of a chemotherapeutic drug.

The non-invasive nature and potential for sustained release make transdermal drug administration an appealing treatment option for cancer therapy. However, the strong barrier of the stratum corneum (SC) poses a challenge for the penetration of hydrophilic chemotherapy drugs such as 5-fluorouracil (5-FU). Due to its biocompatibility and capacity to increase drug solubility and permeability, especially when paired with chemical enhancers, such as oleic acid (OA), which is used in this work, choline glycinate ([Cho][Gly]) has emerged as a potential substance for transdermal drug delivery. In this work, we examined the possibility of transdermal delivery of 5-FU for the treatment of breast cancer using an ionic hydrogel formulation consisting of [Cho][Gly] with OA. Small angle neutron scattering, rheological analysis, field emission scanning electron microscopy, and dynamic light scattering analysis were used to characterize the ionic hydrogel. The non-covalent interactions present between [Cho][Gly] and OA were investigated by computational simulations and FTIR spectroscopy methods. When subjected to in vitro drug permeation using goat skin in a Franz diffusion cell, the hydrogel demonstrated sustained release of 5-FU and effective permeability in the order: [Cho][Gly]-OA gel > [Cho][Gly] > PBS (control). The hydrogel also demonstrated 92% cell viability after 48 hours for the human keratinocyte cell line (HaCaT cells) as well as the normal human cell line L-132. The breast cancer cell line MCF-7 and the cervical cancer cell line HeLa were used to study in vitro cytotoxicity that was considerably affected by the 5-FU-loaded hydrogel. These results indicate the potential of the hydrogel as a transdermal drug delivery vehicle for the treatment of breast cancer.

Multifunctional Ionic Hydrogel-Based Transdermal Delivery of 5-Fluorouracil for the Breast Cancer Treatment.

Transdermal drug delivery systems (TDDS) are a promising and innovative approach for breast cancer treatment, offering advantages such as noninvasiveness, potential for localized and prolonged drug delivery while minimizing systemic side effects through avoiding first-pass metabolism. Utilizing the distinctive characteristics of hydrogels, such as their biocompatibility, versatility, and higher drug loading capabilities, in the present work, we prepared ionic hydrogels through synergistic interaction between ionic liquids (ILs), choline alanine ([Cho][Ala]), and choline proline ([Cho][Pro]) with oleic acid (OA). ILs used in the study are biocompatible and enhance the solubility of 5-fluorouracil (5-FU), whereas OA is a known chemical penetration enhancer. The concentration-dependent (OA) change in morphological aggregates, that is, from cylindrical micelles to worm-like micelles to hydrogels was formed with both ILs and was characterized by SANS measurement, whereas the interactions involved were confirmed by FTIR spectroscopy. The hydrogels have excellent mechanical properties, which studied by rheology and their morphology through FE-SEM analysis. The in vitro skin permeation study revealed that both hydrogels penetrated 255 times ([Cho][Ala]) and 250 times ([Cho][Pro]) more as compared to PBS after 48 h. Those ionic hydrogels exhibited the capability to change the lipid and keratin arrangements within the skin layer, thereby enhancing the transdermal permeation of the 5-FU. Both ionic hydrogels exhibit excellent biocompatibility with normal cell lines (L-132 cells) as well as cancerous cell lines (MCF-7 cells), demonstrating over 92% cell viability after 48 h in both cell lines. In vitro, the cytotoxicity of the 5-FU-loaded hydrogels was evaluated on MCF-7 and HeLa cell lines. These results indicate that the investigated biocompatible and nontoxic ionic hydrogels enable the transdermal delivery of hydrophilic drugs, making them a viable option for effectively treating breast cancer.

Preparation of sodium alginate/Cur-PLA hydrogel beads for curcumin encapsulation.

The low bioavailability of hydrophobic compounds, however, limits their medicinal use. Hydrogel beads made of biopolymers can be employed as controlled delivery systems and as a carrier to carry curcumin molecules. In this study, encapsulation of curcumin is done within the hydrogel by using Polylactic acid. The prepared SA/Cur-PLA and SA/Cur beads were examined using FTIR, SEM, TGA, NMR, and, XRD to study the interaction between drug and polymer. The developed bead's curcumin encapsulation efficiency was found to be 81.47 % in SA/Cur-PLA. Curcumin's release kinetics have been studied in systems (SGF, pH 1.2, and SCF, pH 7.4) that simulate oral consumption, which possess good pH sensitivity. The in vitro drug release studies of SA/Cur-PLA beads suggest that the curcumin release was significantly increased in a controlled manner and within 12 h, the cumulative release of curcumin was accomplished. In vitro hemolysis study shows a 7.93 % hemolysis rate which suggests that the produced bead is hemocompatible. For SA/Cur-PLA and SA/Cur, cytotoxicity evaluation and antimicrobial study was performed. Results show that both hydrogels are cytocompatible and antimicrobial in nature. It was found that biopolymer-based hydrogel beads enhanced the bioavailability of curcumin, antioxidant, biodegradable, and considered an effective carrier for the oral delivery of several hydrophobic nutraceuticals.

Development of Simple Fluorescence Analytical Strategy for the Detection of Triazophos Using Greenish-Yellow Emissive Carbon Dots Derived from Curcuma longa.

This study describes a new method for synthesizing water-soluble carbon dots (CDs) using "Curcuma longa" (green source) named CL-CDs via a single-step hydrothermal process. The as-synthesized CL-CDs exhibited greenish-yellow fluorescence at 548 nm upon excitation at 440 nm. It shows good water stability and exhibits a quantum yield of 19.4%. The developed probe is utilized for sensing triazophos (TZP) pesticide via a dynamic quenching mechanism, exhibiting favorable linearity ranging from 0.5-500 µM with a limit of detection of 0.0042 µM. The as-prepared CL-CDs probe was sensitive and selective towards TZP. Lastly, the successful application of the CL-CDs-based fluorescent probe in water and rice samples highlights its potential as a reliable and efficient method for the detection of TZP in various real sample matrices. Eventually, bioimaging and biocompatibility aspects of CL-CDs have been assessed on Saccharomyces cerevisiae (yeast) cell and lung cancer (A549) cell lines, respectively.

Fluorescence "Turn OFF-ON" detection of Fe3+ and propiconazole pesticide using blue emissive carbon dots from lemon peel.

In this study, water-soluble carbon dots (CDs) were employed as a novel fluorescence "turn OFF-ON" sensor to detect Fe3+ ions in pharmaceutical sample and propiconazole (PC) in food samples. Blue fluorescent "LPCDs" are synthesized from the lemon peel that exhibited emission at 468 nm when excited at 378 nm. The average size of the as-prepared LPCDs is 2.03 nm, displaying a quantum yield of 32 %. Fluorescence "turn OFF-ON" strategy was developed for sensing of Fe3+ ion and PC, demonstrating favorable linearity in the range of 0.5-180 µM and 0.1-40 µM with the detection limits of 0.18 µM and 0.054 µM for Fe3+ and PC, respectively. Further, LPCDs-loaded cellulose paper was used as visual reader to detect Fe3+ and PC. This approach was effectively applied to detect Fe3+ and PC in pharmaceutical and vegetable samples.

Advances in Ultra-small Fluorescence Nanoprobes for Detection of Metal Ions, Drugs, Pesticides and Biomarkers.

Identification of trace level chemical species (drugs, pesticides, metal ions and biomarkers) plays key role in environmental monitoring. Recently, fluorescence assay has shown significant advances in detecting of trace level drugs, pesticides, metal ions and biomarkers in real samples. Ultra-small nanostructure materials (metal nanoclusters (NCs), quantum dots (QDs) and carbon dots (CDs)) have been integrated with fluorescence spectrometer for sensitive and selective analysis of trace level target analytes in various samples including environmental and biological samples. This review summarizes the properties of metal NCs and ligand chemistry for the fabrication of metal NCs. We also briefly summarized the synthetic routes for the preparation of QDs and CDs. Advances of ultra-small fluorescent nanosensors (NCs, QDs and CDs) for sensing of metal ions, drugs, pesticides and biomarkers in various sample matrices are briefly discussed. Additionally, we discuss the recent challenges and future perspectives of ultra-small materials as fluorescent sensors for assaying of wide variety of target analytes in real samples.

Review on Metal-Organic Framework Classification, Synthetic Approaches, and Influencing Factors: Applications in Energy, Drug Delivery, and Wastewater Treatment.

Metal ions or clusters that have been bonded with organic linkers to create one- or more-dimensional structures are referred to as metal-organic frameworks (MOFs). Reticular synthesis also forms MOFs with properly designated components that can result in crystals with high porosities and great chemical and thermal stability. Due to the wider surface area, huge pore size, crystalline nature, and tunability, numerous MOFs have been shown to be potential candidates in various fields like gas storage and delivery, energy storage, catalysis, and chemical/biosensing. This study provides a quick overview of the current MOF synthesis techniques in order to familiarize newcomers in the chemical sciences field with the fast-growing MOF research. Beginning with the classification and nomenclature of MOFs, synthesis approaches of MOFs have been demonstrated. We also emphasize the potential applications of MOFs in numerous fields such as gas storage, drug delivery, rechargeable batteries, supercapacitors, and separation membranes. Lastly, the future scope is discussed along with prospective opportunities for the synthesis and application of nano-MOFs, which will help promote their uses in multidisciplinary research.

Synthesis of blue fluorescent molybdenum nanoclusters with novel terephthaldehyde-cysteine Schiff base for detection of pyrophosphate.

In this work, terephthaldehyde-cysteine-molybdenum nanoclusters (TPA-Cys-MoNCs) were synthesized by using terephthaldehyde-cysteine (TPA-Cys) Schiff base as a novel ligand. The as-synthesized TPA-Cys-MoNCs showed blue fluorescence under UV lamp at 365 nm, displaying emission peak at 455 nm when excited at 340 nm. The fluorescent TPA-Cys-MoNCs are used as a probe for sensitive assay of pyrophosphate (PPi) via fluorescence quenching mechanism. The emission peak intensity of TPA-Cys-MoNCs at 455 nm exhibited a linear quenching with increasing amount of PPi. As a result, quantitative assay was developed for the detection of PPi (0.01-200 µM) with the detection limit of 0.9 nM. The developed probe was successfully demonstrated for the detection of PPi in biofluids (urine and plasma).

Microwave-Assisted Synthesis of Red Emitting Copper Nanoclusters Using Trypsin as a Ligand for Sensing of Pb2+ And Hg2+ Ions in Water and Tobacco Samples.

In this work, a microwave assisted method was developed for synthesis of red fluorescent copper nanoclusters (NCs) using trypsin as a template (trypsin-Cu). The as-synthesized trypsin-Cu NCs are stable and water soluble, exhibiting fluorescence emission at 657 nm when excited at 490 nm. The as-prepared red-emitting trypsin-Cu NCs were characterized by using several analytical techniques such as ultraviolet-visible (UV-Vis) and fluorescence, fluorescence lifetime, Fourier transform infrared, and X-ray photoelectron spectroscopic techniques. Red-emitting trypsin-Cu NCs acted as a nanosensor for sensing both Pb2+ and Hg2+ ions through fluorescence quenching. Using this approach, good linearities are observed in the range of 0.1-25 and of 0.001-1 µM with the lower limit of detection of 14.63 and 56.81 nM for Pb2+ and Hg2+ ions, respectively. Trypsin-Cu NCs-based fluorescence assay was successfully applied to detect both Hg2+ and Pb2+ ions in water and tobacco samples.

Folic acid functionalized molybdenum oxide quantum dots for the detection of Cu2+ ion and alkaline phosphatase via fluorescence turn off-on mechanism.

The assay of alkaline phosphatase (ALP) plays a key role in the diagnosis of various diseases. Herein, folic acid functionalized molybdenum oxide quantum dots (FA-MoOx QDs) are explored as fluorescence "turn- off and on" probes for assaying of Cu2+ ion and ALP, respectively. This fluorescence sensing strategy was based on the quenching of emission peak of FA-MoOx QDs at 445 nm by Cu2+ ion, followed by restoring of emission peak selectively with ALP. Based on the quenching and restoring of FA-MoOx QDs emission intensity, quantitative assay was developed for the detection of Cu2+ ion (0.20 - 500 µM) and ALP (0.06 - 150 U/L) with detection limits of 29 nM and 0.026 U/L, respectively. The developed FA-MoOx QDs-based fluorescence "turn- off and on" strategy exhibited satisfactory results for assaying of ALP in biofluids.

Ionic Liquid-Based Surfactants: Recent Advances in Their Syntheses, Solution Properties, and Applications.

The impetus for the expanding interest in ionic liquids (ILs) is their favorable properties and important applications. Ionic liquid-based surfactants (ILBSs) carry long-chain hydrophobic tails. Two or more molecules of ILBSs can be joined by covalent bonds leading, e.g., to gemini compounds (GILBSs). This review article focuses on aspects of the chemistry and applications of ILBSs and GILBSs, especially in the last ten years. Data on their adsorption at the interface and micelle formation are relevant for the applications of these surfactants. Therefore, we collected data for 152 ILBSs and 11 biamphiphilic compounds. The head ions of ILBSs are usually heterocyclic (imidazolium, pyridinium, pyrrolidinium, etc.). Most of these head-ions are also present in the reported 53 GILBSs. Where possible, we correlate the adsorption/micellar properties of the surfactants with their molecular structures, in particular, the number of carbon atoms present in the hydrocarbon "tail". The use of ILBSs as templates for the fabrication of mesoporous nanoparticles enables better control of particle porosity and size, hence increasing their usefulness. ILs and ILBSs form thermodynamically stable water/oil and oil/water microemulsions. These were employed as templates for (radical) polymerization reactions, where the monomer is the "oil" component. The formed polymer nanoparticles can be further stabilized against aggregation by using a functionalized ILBS that is co-polymerized with the monomers. In addition to updating the literature on the subject, we hope that this review highlights the versatility and hence the potential applications of these classes of surfactants in several fields, including synthesis, catalysis, polymers, decontamination, and drug delivery.

Concentration- and Temperature-Responsive Reversible Transition in Amide-Functionalized Surface-Active Ionic Liquids: Micelles to Vesicles to Organogel.

A ubiquitous example of DNA and proteins inspires the scientific community to design synthetic systems that can construct various self-assembled complex nano-objects for high-end physiological functions. To gain insight into judiciously designed artificial amphiphilic structures that through self-assembling form various morphological architectures within a single system, herein, we have studied self-aggregation of amide-functionalized surface-active ionic liquids (AFSAILs) with different head groups in the DMSO/water mixed system. The AFSAIL forms stimuli-responsive reversible micelle and vesicle configurations that coexist with three-dimensional (3D) network structures, the organogel in the DMSO/water mixed system. The self-assembly driving forces, self-organization patterns, network morphologies, and mechanical properties of these network structures have been investigated. With the proven biodegradability and biocompatibility, one can envisage these AFSAILs as the molecules with a new dimension of versatility.

Cellulose in Ionic Liquids and Alkaline Solutions: Advances in the Mechanisms of Biopolymer Dissolution and Regeneration.

This review is focused on assessment of solvents for cellulose dissolution and the mechanism of regeneration of the dissolved biopolymer. The solvents of interest are imidazole-based ionic liquids, quaternary ammonium electrolytes, salts of super-bases, and their binary mixtures with molecular solvents. We briefly discuss the mechanism of cellulose dissolution and address the strategies for assessing solvent efficiency, as inferred from its physico-chemical properties. In addition to the favorable effect of lower cellulose solution rheology, microscopic solvent/solution properties, including empirical polarity, Lewis acidity, Lewis basicity, and dipolarity/polarizability are determinants of cellulose dissolution. We discuss how these microscopic properties are calculated from the UV-Vis spectra of solvatochromic probes, and their use to explain the observed solvent efficiency order. We dwell briefly on use of other techniques, in particular NMR and theoretical calculations for the same purpose. Once dissolved, cellulose is either regenerated in different physical shapes, or derivatized under homogeneous conditions. We discuss the mechanism of, and the steps involved in cellulose regeneration, via formation of mini-sheets, association into "mini-crystals", and convergence into larger crystalline and amorphous regions. We discuss the use of different techniques, including FTIR, X-ray diffraction, and theoretical calculations to probe the forces involved in cellulose regeneration.

Stimuli Responsive, Self-Sustainable, and Self-Healable Functionalized Hydrogel with Dual Gelation, Load-Bearing, and Dye-Absorbing Properties.

The motivation for designing low-molecular-weight gelators with self-healing characteristics originates from elegant examples in biology such as vines of the genus Aristolochia whose internal secondary growth exhibits rapid self-healing in their stems. In the present work, we had explored the stimuli-responsive dual gelation characteristics for the ester-functionalized surfactant (4-(2-(hexadecyloxy)-2-oxoethyl)-4-methylmorpholin-4-ium bromide, C16EMorphBr) in aqueous medium at 7.20% (w/v) critical gel concentration and pH 7.4. The hydrogel provides an excellent platform to study dynamic phase behavior within a supramolecular network as it exhibits transformation from a fibrillar opaque hydrogel to a transparent hydrogel upon heating. Molecular interactions, arrangement within the supramolecular framework, and mechanical properties of the hydrogels were characterized using Fourier transform infrared, small-angle neutron scattering, rheological analysis, and tensile strength and cyclic loading-unloading tests. The fibrillar opaque gel has been characterized for its morphology using scanning electron microscopy, field emission scanning electron microscopy, transmission electron microscopy, and atomic force microscopy. The self-sustained, self-healable porous fibrillar opaque xerogel was further explored for selectively absorbing anionic dyes and for its load-bearing characteristics. We conclude a perspective on designing a new-age gelator that can open entirely new avenues in environmental protection and wearable "smart" devices.

Trypsin mediated one-pot reaction for the synthesis of red fluorescent gold nanoclusters: Sensing of multiple analytes (carbidopa, dopamine, Cu2+, Co2+ and Hg2+ ions).

Herein, we fabricated fluorescent gold nanoclusters (Au NCs) by using trypsin as a ligand. The fabricated trypsin-Au NCs emit bright red color fluorescence upon the exposure of 365 nm UV light. The trypsin-Au NCs are stable and well dispersed in water, which exhibited strong red emission peak at 665 nm upon excitation wavelength of 520 nm. The red fluorescence of trypsin-Au NCs was greatly quenched by the addition of multiple analytes such as drugs (carbidopa and dopamine) and three divalent metal ions (Cu2+, Co2+ and Hg2+ ion). As a result, a novel fluorescence "turn-off" probe was developed for the detection of the above analytes with good selectivity and sensitivity. This method exhibits the detection limits for carbidopa, dopamine, Cu2+, Co2+ and Hg2+ ions are 6.5, 0.14, 5.2, 0.0078, and 0.005 nM, respectively. The trypsin-Au NCs were successfully applied to detect drugs (carbidopa, and dopamine) in pharmaceutical samples and metal ions (Cu2+, Co2+ and Hg2+ ion) in biofluids and water samples, exhibiting good precision and accuracy, which offers a facile analytical strategy for assaying of the above analytes in pharmaceutical and biological samples.

Thermo-Switchable de Novo Ionic Liquid-Based Gelators with Dye-Absorbing and Drug-Encapsulating Characteristics.

An ionic liquid-based surfactant with ester functionality self-aggregates in an aqueous medium and forms ionogels at 8.80% (w/v) concentration at physiological pH. The ionogel exhibited a remarkable change in its appearance with temperature from fibrillar opaque to transparent because of the dynamic changes within its supramolecular structure. This gel-to-gel phase transition occurs below the melting point of the solid ionic liquid. The ionogels were investigated using turbidity, differential scanning calorimetry, scanning electron microscopy (SEM), field emission SEM (FE-SEM), inverted microscopy, transmission electron microscopy imaging, Fourier transform infrared spectroscopy, and rheological measurements. The fibrillar opaque ionogel and transparent ionogel were studied for their ability to absorb dyes (methyl orange and crystal violet) and to encapsulate drugs (diclofenac sodium and imatinib mesylate).

Drug-Induced Micelle-to-Vesicle Transition of a Cationic Gemini Surfactant: Potential Applications in Drug Delivery.

An impetus for the sustained interest in the formation of vesicles is their potential application as efficient drug-delivery systems. A simple approach for ionic surfactants is to add a vesicle-inducing drug of opposite charge. In ionic gemini surfactants (GSs) two molecules are covalently linked by a spacer. Regarding drug delivery, GSs are more attractive candidates than their single-chain counterparts because of their high surface activity and the effect on the physicochemical properties of their solutions caused by changing the length of the spacer and inclusion of heteroatoms therein. Herein, the effect of the (anionic) anti-inflammatory drug diclofenac sodium (DS) on the morphology of aqueous micellar aggregates of gemini surfactant hexamethylene-1,6-bis (dodecyldimethylammonium) dibromide (12-6-12) at 25 °C is reported. Several independent techniques are used to demonstrate drug-induced micelle-to-vesicle transition. These include UV/Vis spectrophotometry, dynamic light scattering, TEM, and small-angle neutron scattering. The micelles are transformed into vesicles with increasing [DS]/[12-6-12] molar ratio; precipitation of the catanionic (DS-GS) complex then occurred, followed by partial resuspension of the weakly anionic precipitate. The stability of some of the prepared vesicles at human body temperature shows their potential use in drug delivery.

Ionic Liquid-Based Catanionic Coacervates: Novel Microreactors for Membrane-Free Sequestration of Dyes and Curcumin.

Surfactant-mediated coacervates are termed as the new age microreactors for their ability to spontaneously sequester the molecules with varied polarities and functionalities. Efforts to emulate this applicability of coacervates through synthetic control of surfactant structures are finding success; however, there is little understanding of how to translate these changes into tailor-made properties. Herein, we designed 3-methyl-1-(octyloxycarbonylmethyl)imidazolium bromide (C8EMeImBr), an ester-functionalized ionic liquid-based surfactant, which shows better surface active properties than the nonfunctionalized and conventional cationic surfactant and forms complex coacervates over the broad range of concentration with sodium salicylate (NaSal). Mono- and divalent cations as well as ionic strength, viscosity, and time-dependent stability of the coacervates had also been addressed in order to study whether these coacervates could work as microreactors to encapsulate various molecules. The anionic charged complex coacervates with sponge morphology and honey comb-like interior show good efficiency to sequester cationic dyes from water because of electrostatic and hydrophobic interactions and good encapsulation efficiency for curcumin owing to their high surface area. Results suggest that ionic liquid-based coacervates studied here could be exploited as a novel low-cost, effective, and environmentally benign alternative to sequester dyes from the contaminated water and their recovery.

Temperature-dependent solvatochromic probe behavior within ionic liquids and (ionic liquid + water) mixtures.

Spectroscopic responses of absorbance probes, betaine dye 33, N,N-diethyl-4-nitroaniline, and 4-nitroaniline, and fluorescence dipolarity probes, pyrene (Py) and pyrene-1-carboxaldehyde (PyCHO) within ionic liquids (ILs) 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]), and aqueous mixtures of [bmim][BF4] are used to assess the changes in important physicochemical properties with temperature in the range 10-90 degrees C. ETN obtained from betaine dye 33, indicating dipolarity/polarizability and/or hydrogen bond donating (HBD) acidity, decreases linearly with increasing temperature within the two ILs. Changes in Kamlet-Taft parameters dipolarity/polarizability (pi*), HBD acidity (alpha), and HB accepting (HBA) basicity (beta) with temperature show interesting trends. While pi* and alpha decrease linearly with increasing temperature within the two ILs, beta appears to be independent of the temperature. Similar to ETNand pi*, the first-to-third band intensity ratio of probe Py also decreases linearly with increasing temperature within the ILs. The lowest energy fluorescence maxima of PyCHO, though it decreases significantly within water as the temperature is increased from 10 to 90 degrees C, it does not change within the two ILs investigated. The temperature dependence of the dipolarity/polarizability as manifested via betaine dye 33 behavior is found to be more within the aqueous mixtures of [bmim][BF4] as compared to that within neat [bmim][BF4] or neat water. The sensitivity of pi* toward temperature increases as IL is added to water and that of alpha decreases. The temperature dependent Py behavior shows no clear-cut trend within aqueous mixtures of [bmim][BF4]; insensitivity of the PyCHO response toward temperature change is reasserted within aqueous IL mixtures. All-in-all, the temperature-dependent behavior of solvatochromic probes within [bmim][PF6], [bmim][BF4], and aqueous mixtures of [bmim][BF4] is found to depend on the identity of the probe.