Chemical modification of ß-cyclodextrin towards hydrogel formation.

ß-CD is a cyclic oligosaccharide, which has trunked cone like structure. The unique structure makes it efficient for numerous applications. Though, the native ß-CD has many issues like low solubility, absence of sufficient functionalities and lower complexation ability with guest molecules. One of the most effective paths to increase the efficiency of cyclodextrins is the generation of polycyclodextrins. In this perspective article, we have summarized the recent reports on the synthetic methods towards the modification of ß-CD. Besides, this article reviews the current improvements of two types of ß-CD centered supramolecular hydrogels: one is supramolecular hydrogels prepared from CD-based poly(pseudo)rotaxanes and the other is supramolecular hydrogels developed through the host-guest interaction between small guest molecules and CDs. The Polycyclodextrins have established noteworthy applications in several areas ranging from adsorbents for organic pollutants removal to effective carriers of bioactive agents.

Chitosan based titanium and iron oxide hybrid bio-polymeric nanocomposites as potential corrosion inhibitor for mild steel in acidic medium.

Biopolymer chitosan (CS), chitosan grafted acrylamide based titanium dioxide (CS-g-PAM/TiO2) and magnetite (CS-g-PAM/Fe3O4) hybrid nanocomposites have been synthesized through free radical graft co-polymerization and successfully validated as corrosion inhibitors for mild steel in 15 % HCl solution. The synthesized compounds have been characterized through FTIR, APC, XRD and TEM. The thermal stability of the nanocomposites was established by TGA. The anticorrosive performance was determined through gravimetric measurements and by electrochemical study. According to EIS technique it was observed that CS-g-PAM/TiO2 and CS-g-PAM/Fe3O4 showed maximum 97.19 % and 95.49 % efficiency respectively. Langmuir adsorption isotherm is obeyed in each case. The activation and adsorption parameters have been determined from isotherm study. FESEM and AFM confirmed better adsorption layer formed by composites over mild steel surface. The elemental composition of the metal samples was proved by the XPS investigation. DFT and ANOVA test further corroborates the experimental results.

pH-Responsive Copolymeric Network Gel Using Methacrylated ß-Cyclodextrin for Controlled Codelivery of Hydrophilic and Hydrophobic Drugs.

In medical science, sometimes two drugs with different solubilities are simultaneously required in combination to treat various diseases. Herein, a pH-responsive, copolymeric, antioxidant, biocompatible, and chemically crosslinked network gel is prepared to explore its capability as a matrix for controlled release of both hydrophobic [ibuprofen (IB)] and hydrophilic [tetracycline hydrochloride (TCH)] drugs, simultaneously. This three-dimensional ß-CD-Meth-cl-(PHPMA-co-PAAc) network hydrogel is synthesized via two steps: (I) methacrylation of ß-cyclodextrin and (II) grafting of poly(hydroxypropyl methacrylate) and poly(acrylic acid), followed by crosslinking of poly(ethylene glycol) diacrylate onto the backbone of methacrylated ß-cyclodextrin (ß-CD-Meth). The successful synthesis of the hydrogel is confirmed using several physiochemical characterizations. The ß-CD-Meth-cl-(PHPMA-co-PAAc) hydrogel has an excellent network-like surface morphology. The potential pH-responsive high swelling behavior and excellent shrinking features suggest the reversible nature of the synthesized gel. Besides, rheological analyses affirm its excellent viscoelastic nature. This network gel is biodegradable and its non-cytotoxic nature toward human dermal fibroblast cells is demonstrated. Moreover, the dual drug release pattern from the copolymer under both in vitro and in vivo conditions portrays that this hydrogel has superior ability to be used as a controlled release matrix for both hydrophobic and hydrophilic drugs (TCH and IB) with varying solubilities concurrently.

ß-Cyclodextrin-Based Ultrahigh Stretchable, Flexible, Electro- and Pressure-Responsive, Adhesive, Transparent Hydrogel as Motion Sensor.

In the present work, a multiple-stimuli-responsive hydrogel has been synthesized via polymerization of acrylamide (AAm) and N-hydroxy methyl acrylamide (HMAm) on ß-cyclodextrin (ß-CD). The synthesized hydrogel ß-CD-g-(pAAm/pHMAm) exhibited various striking features like ultrahigh stretchability (>6000%), flexibility, stab resistivity, self-recoverability, electroresponsiveness, pressure-responsiveness, adhesiveness, and high transparency (>90%). Besides, the hydrogel has demonstrated enhanced biocompatibility, UV resistance, and thermoresponsive shape memory behaviors. On the basis of these attractive characteristics of the hydrogel, a flexible pressure sensor for the real-time monitoring of human motion with superior biocompatibility and transparency was fabricated. Moreover, due to the nanofibrillar surface morphology of the ß-CD-g-(pAAm/pHMAm) hydrogel, the sensor based on the gel exhibited high sensitivity (0.053 kPa-1 for 0-3.3 kPa). The flexible sensor demonstrates very fast response time (130 ms-210 ms) with adequate stability (5000 cycles). Interestingly, the sensor can rapidly sense both robust (index finger and wrist) motions as well as tiny (swallowing and phonation) physiological actions. In addition, this adhesive hydrogel patch also acts as a potential carrier for the sustained topical release of (∼80.8% in 48 h) the antibiotic drug gentamicin sulfate.

Poly(N-vinyl imidazole) Cross-Linked ß-Cyclodextrin Hydrogel for Rapid Hemostasis in Severe Renal Arterial Hemorrhagic Model.

A unique facile process has been adopted for fast assembly of a poly(N-vinyl imidazole) cross-linked ß-cyclodextrin hydrogel through microwave-assisted free radical polymerization, using N,N'-methylenebis(acrylamide) cross-linker. The copolymer possesses positive surface charge, one of the characteristic properties of an ideal hemostatic hydrogel. The functionalized imidazole-based hydrogel demonstrates rapid, superior blood coagulation kinetics under in vitro and in vivo conditions. On application to a major renal arterial hemorrhagic model, this hydrogel shows better blood clotting kinetics, leading to complete hemostasis in as few as ∼144 ± 7 s. Additionally, 350 µL of whole blood was clotted instantly, in ∼35 s, and therefore, reinforcing its hemostatic potential. The hydrogel demonstrates excellent biocompatibility, when seeded with human dermal fibroblast cells, retaining the native property of its predecessor. In addition, the hydrogel presents excellent hemocompatibility when tested with whole blood with the highest hemolytic ratio of 1.07 ± 0.05%. Moreover, it also demonstrates potential as a carrier for sustained release of an anesthetic drug, lidocaine hydrochloride monohydrate (∼83% in 24 h). The rapid hemostatic behavior of the hydrogel is coupled with its cytocompatibility and hemocompatibilty properties along with controlled drug release characteristics. These behaviors evidently demonstrate it to be an excellent alternative for a superior hemostatic material for severe hemorrhagic conditions.

Dextran based amphiphilic self-assembled biopolymeric macromolecule synthesized via RAFT polymerization as indomethacin carrier.

This work demonstrates a facile pathway to develop a biopolymer based amphiphilic macromolecule through reversible addition-fragmentation chain transfer (RAFT) polymerization, using dextran (a biopolymer) as starting material. Also, a new hydrophobic monomer [2-methyl-acrylic acid 1-benzyl-1H-[1,2,3] triazol-4-ylmethyl ester (MABTE)] has been synthesized using methacrylic acid via "click" approach. The resultant copolymer displays controlled radical polymerization characteristics: narrow polydispersity (Ð) and controlled molecular weight as obtained through advanced polymer chromatography (APC) analysis. In aqueous solution, the copolymer can proficiently be self-assembled to provide micellar structure, which has been evidenced from field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) analyses. The in-vitro cytotoxicity study illustrates the nontoxic nature of the copolymer up to 100 µg/mL polymer concentration. The copolymer has been found to be worthy as an efficient carrier for the sustained release of hydrophobic drug: Indomethacin (IND).

Dual Functionalized Injectable Hybrid Extracellular Matrix Hydrogel for Burn Wounds.

Low strength and rapid biodegradability of acellular dermal matrix (ADM) restrict its wider clinical application as a rapid cell delivery platform in situ for management of burn wounds. Herein, the extracted ADM was modified by a dual cross-linking approach with ionic crosslinking using chitosan and covalent cross-linking using an iodine-modified 2,5-dihydro-2,5-dimethoxy-furan cross-linker, termed as CsADM-Cl. In addition, inherent growth factors and cytokines were found to be preserved in CsADM-Cl, irrespective of ionic/covalent crosslinking. CsADM-Cl demonstrated improvement in post crosslinking stiffness with a decreased biodegradation rate. This hybrid crosslinked hydrogel supported adhesion, proliferation, and migration of human foreskin-derived fibroblasts and keratinocytes. Also, the angiogenic potential of CsADM-Cl was manifested by chick chorioallantoic membrane assay. CsADM-Cl showed excellent antibacterial activity against Escherichia coli and Staphylococcus aureus. Moreover, CsADM-Cl treated full thickness burn wounds and demonstrated rapid healing marked with superior angiogenesis, well-defined dermal-epidermal junctions, mature basket weave collagen deposition, and development of more pronounced secondary appendages. Altogether, the bioactive CsADM-Cl hydrogel established significant clinical potential to support wound healing as an apt injectable antibacterial matrix to encounter unmet challenges concerning critical burn wounds.

Crosslinked chitosan embedded TiO2 NPs and carbon dots-based nanocomposite: An excellent photocatalyst under sunlight irradiation.

Herein, a new hybrid nanocomposite, comprising of titania nanoparticles (TiO2 NPs) and carbon dots (CDs) deposited polyvinyl imidazole crosslinked chitosan [cl-Ch-p(VI)/TiO2NPs-CDs] has been developed. The nanocomposite has been synthesised by in-situ deposition of TiO2 NPs and CDs onto the surface of the copolymer under microwave irradiation. To the best of our knowledge, this in-situ approach has effectively been applied for the first time to fabricate green fluorescent CDs from sugar cane juice at moderate temperature (75 °C) under microwave irradiation. The developed nanocomposite has been characterized using UV-Vis spectroscopy, 13C NMR, XRD, HR-TEM, STEM and XPS analyses. The results suggest that the successful deposition of TiO2 NPs and CDs onto the surface of crosslinked chitosan is achieved. The experimental studies indicate that the NPs/CDs-impregnated nanocomposite allows efficient photocatalytic degradation of toxic organic compounds (~98.6% degradation of 2,4-dicholorophenol, ~95.8% degradation of Reactive Blue 4, ~98.2% degradation of Reactive Red 15) in the presence of sunlight. Finally, LC-MS analysis of the resultant degraded materials reveals the formation of organic molecules with lower molecular mass.

Development of a Thermoresponsive Polymeric Composite Film Using Cross-Linked ß-Cyclodextrin Embedded with Carbon Quantum Dots as a Transdermal Drug Carrier.

Polymeric nanocomposite films are used as promising transdermal drug carriers because of the improved patient compliance, easy application on skin, and noninvasiveness. A thermoresponsive polymeric composite film has been developed here through the deposition of carbon quantum dots (CQDs) on functionalized ß-cyclodextrin (ß-CD). The composite has been developed by grafting of poly(N-vinyl caprolactam) on ß-CD, followed by cross-linking of diethylene glycol dimethacrylate and subsequent deposition of CQDs. CQDs have been prepared from waste pomegranate peels via a hydrothermal method. To enlighten the thermoresponsive nature of the composite film, lower critical solution temperature, as well as temperature-dependent swelling behavior, has been studied. The composite demonstrates excellent rheological features. The developed polymeric composite film is nontoxic toward NIH 3T3 fibroblast cell lines. On the deposition of CQDs on the copolymer, the penetration power and fluorescent property have been improved, which help to track the cells in vitro. This film is worthy to be applied to the skin. It can efficiently load lidocaine hydrochloride monohydrate (LHM). In vitro and ex vivo skin permeation profiles reveal the sustained release behavior of loaded LHM at average skin temperature and pH.

Novel nanocomposite derived from ZnO/CdS QDs embedded crosslinked chitosan: An efficient photocatalyst and effective antibacterial agent.

A novel nanocomposite (cl-Ch-pMAc@ZnO/CdSQDs) has been developed under microwave irradiation via fabrication of ZnO/CdS quantum dots on anionically functionalized chitosan [i.e. poly (methacrylic acid) crosslinked chitosan (cl-Ch-pMAc) in the presence of diethylene glycol dimethacrylate (DEGDMA) crosslinker]. The structural, morphological and chemical/physical properties of crosslinked chitosan and the nanocomposites have been investigated using 13C nuclear magnetic resonance spectroscopy (13C NMR spectroscopy), high resolution-transmission electron microscopy (HR-TEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) analyses. The nanocomposite demonstrates outstanding efficacy towards the photocatalytic degradation of cationic dyes [malachite green (MG), and safranin (SF)] and toxic organic molecule 2,4-dichloro phenol (2,4-DCP) under the exposure of sunlight. Liquid chromatography mass spectroscopy (LC-MS) studies predict that small molecules are produced by degradation. Moreover, the composite exhibits excellent antibacterial activity towards E-coli and B. subtilis. Finally, the nanocomposite can be regenerated effectively with changing the solution pH and also shows 5 times reusability without significant reduction on its efficiency.

Removal of toxic pollutants from aqueous media using poly (vinyl imidazole) crosslinked chitosan synthesised through microwave assisted technique.

Water contamination owing to the presence of toxic organic chemicals/heavy metals are considered to be one of the serious global environmental issues. Various advanced polymeric materials have been developed and used for the separation/removal of these contaminants. To consider the afore-mentioned problem, recently in authors' laboratory, an efficient biopolymeric adsorbent has been prepared using poly (vinyl imidazole) crosslinked chitosan (cl-Ch-pVI) through a simple microwave-assisted free radical polymerization technique. The structural characteristics of the developed hydrogel have been studied in details. The copolymer cl-Ch-pVI reveals excellent gel characteristics, demonstrates superior efficiency towards removal of toxic Cr(VI) from aqueous solution. Moreover, the copolymer also shows outstanding adsorption capacity to remediation of organic dye reactive black 5 (RB5), which manifests the potential application of synthesised copolymer in wastewater treatment.

Graft copolymeric flocculant using functionalized starch towards treatment of blast furnace effluent.

Herein, a novel binary graft copolymeric flocculant [St-g-(PAAm-co-PMETAC)] has been developed using starch, polyacrylamide (PAAm) and poly (2-methacryloyloxy ethyl trimethyl ammonium chloride) (PMETAC). The copolymer has been synthesised by grafting of PAAm and PMETAC chains on starch backbone using free radical polymerization. FTIR and 1H NMR spectral analyses have been used for structural confirmation of developed copolymer. Determination of molecular weight reveals that after grafting of PAAm and PMETAC on starch, the molecular weight as well as radius of gyration have been increased as compared to pristine starch. The surface morphologies of starch and St-g-(PAAm-co-PMETAC) have been assessed by FESEM analysis. TGA/DTG along with MS analyser is able to track the pre-specified compounds over the entire period of degradation temperature. The synthesised graft copolymer i.e. St-g-(PAAm-co-PMETAC) demonstrates brilliant efficiency as flocculant towards the treatment of blast furnace effluent generated in integrated steel plant.

Amphiphilic graft copolymeric micelle using dextrin and poly (N-vinyl caprolactam) via RAFT polymerization: Development and application.

Dextrin and poly (N-vinyl caprolactam) based amphiphilic graft copolymer has recently been developed using RAFT polymerization. The prepared graft copolymer has been characterized in details using FTIR and 1H NMR spectral analyses, GPC, TGA, FESEM, TEM and DLS analyses. GPC analysis results indicate that the polymerization is controlled, while the LCST value of the copolymer suggests that the synthesized copolymer demonstrates sol-gel behaviour on applying temperature. FESEM and TEM analyses envisage that the graft copolymer has spherical morphology with nanoscale dimension. DLS study reveals that the micellar size vary with change of pH and temperature, demonstrating the dual-responsive behaviour of the graft copolymer. Finally, the developed graft copolymer shows worthy efficacy towards the pH and thermo-responsive release of encapsulated pyrene in sustained manner.

Synthesis of triblock copolymeric micelle based on poly (ethylene glycol) and poly (vinyl acetate) through reversible addition-fragmentation chain transfer polymerization.

HYPOTHESIS: Polymeric micelles are fabricated by the self-aggregation of amphiphilic polymers in aqueous medium. Amphiphilic block copolymers consist of hydrophobic and hydrophilic blocks. The hydrophilic blocks form corona, while hydrophobic blocks produce core of the micelle. EXPERIMENTS: In the present manuscript, a triblock copolymer derived from poly (ethylene glycol) and poly (vinyl acetate) (PVAc-b-PEG200-b-PVAc) has been prepared via reversible addition-fragmentation chain transfer polymerization. Its structural properties as well as micellar stability have been studied and application as dye carrier has been discussed in details. FINDINGS: The GPC analysis shows the low polydispersity of the developed copolymer that signifies the controlled nature of polymerization. The copolymer demonstrates long-term micellar stability, which has been determined by dynamic light scattering (DLS) analysis. The block copolymer reveals excellent pH-triggered release behavior of loaded Nile red, which ascertained the dye carrier feature of PVAc-b-PEG200-b-PVAc.

In Situ Silver Nanowire Deposited Cross-Linked Carboxymethyl Cellulose: A Potential Transdermal Anticancer Drug Carrier.

Recently, a novel biopolymeric nanocomposite hydrogel comprised of in situ formed silver nanowires (AgNWs) deposited chemically cross-linked carboxymethyl cellulose (CMC) has been developed, which demonstrates superior efficacy as anticancer drug-curcumin carrier. The cross-linked polymer has been prepared by grafting poly [2-(methacryloyloxy) ethyl trimethylammonium chloride] on CMC using diethylene glycol dimethacrylate cross-linker. The nanocomposite hydrogel has the capability to encapsulate both hydrophobic/hydrophilic transdermal drugs. With variation in reaction conditions/parameters, several composite materials have been synthesized and depending on lower swelling/higher cross-linking and greater gel strength, an optimized grade of nanocomposite hydrogel has been selected. The developed nanocomposite hydrogel is characterized with FTIR/NMR spectra, FESEM/XRD/TGA/AFM/XPS analyses, and UV-visible spectroscopy. Rheological study has been performed to enlighten the gel strength of the composite material. The synthesized nanocomposite hydrogel is biodegradable and nontoxic to mesenchymal stem cells (hMSCs). In vitro release of curcumin suggests that in situ incorporation of AgNWs on cross-linked CMC enhanced the penetration power of nanocomposite hydrogel and released the drug in sustained way (∼62% for curcumin released in 4 days). Ex vivo rat skin permeation study confirms that the drug from both the cross-linked and nanocomposite hydrogel was permeable through the rat skin in controlled fashion. Additionally the curcumin loaded composite hydrogel can efficiently kill the MG 63 cancer cells, which has been confirmed by apoptosis study and therefore, probably be a suitable carrier for curcumin delivery toward cancer cells.