Sensitive Sol-gel Research Articles

Local delivery of gambogic acid to improve anti-tumor immunity against oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC) accounts for nearly 90% of oral cavity malignancies. However, despite significant advances in the last four decades, little improvement has been achieved in the overall survival rates for OSCC patients. While gambogic acid (GA) is a potential candidate compound for treating a variety of malignancies, its anti-cancer impact on OSCC has not to be completely investigated. The tumor immune microenvironment (TIME) has been proven to play a crucial role in the prognosis of cancer patients. Although there are few reports on the T cell activation effect of GA, the regulation of GA on the TIME of OSCC has barely been studied yet. In this study, GA was applied to treat OSCC-bearing mice through in situ controlled release. First, GA-loaded mPEG₂₀₀₀-PCL micelles (GA-MIC) were prepared by the thin-film hydration method to improve the aqueous dispersibility of GA. Second, poly(D, l-lactide)-poly(ethylene glycol)-poly(D, l-lactide) (PLEL) was synthesized for thermosensitive hydrogel preparation. Third, GA-MIC was mixed with PLEL to form an injectable therapeutic hydrogel (GA-MIC-GEL). The anti-tumor and TIME regulation effects of GA-MIC-GEL on tumor-bearing mice were further examined. The results showed that the thermosensitive GA-MIC-GEL with sensitive sol-gel transition characteristics could form hydrogel at 37°C within 24s, facilitating the local delivery and sustained GA release. Biochemical, hematological, and pathological analysis proved that GA-MIC-GEL has good biological safety. Moreover, GA-MIC-GEL promoted an obvious regression of both primary and distant tumors on the OSCC mouse models. Mechanically, GA-MIC-GEL down-regulated the expression of PD-1, increased the frequency of cytotoxic T cells and reduced the immunosuppressive cellular components, which boosted the anti-tumor immunity of OSCC-bearing mice. The constructed thermosensitive hydrogel for local delivery of GA has provided a safe and effective strategy with great potential for OSCC therapy.

The synergistic blood-vessel-embolization of coagulation fusion protein with temperature sensitive nanogels in interventional therapies on hepatocellular carcinoma

• TF-Nannogels realized the synergistic artery embolization by TVI and TACE. • TF-Nanogels improved hypoxic micro-environment, enhanced antitumor immune effects. • TF-Nanogels inhibited tumor metastasis by improving the tumor micro-environment. • TF-Nanogels protects tTF-pHLIPs from rapid degradation, sustains a thromboembolism. As one of the most extensively used clinical treatments for many solid tumors such as liver cancer, trans-arterial embolization (TAE) was greatly limited by postoperative recurrence and metastasis and poor long-term efficacy. In present work, tTF-pHLIPs was entrapped into 3D networks of poly( N -isopropylacrylamide- co -butyl methacrylate) (PIB) nanogels, named as TF-Nanogels, for improving their sustained release and in vivo PK/PD properties by temperature sensitive sol–gel transition of PIB nanogels. TF-Nanogels exhibited a synergistic effect between the extrinsic coagulation of tTF-pHLIPs and intrinsic coagulation of PIB nanogels with negative charges in in vitro clotting assays, and a distinct activation on platelets by CD62P pathways at above 0.1 mg/mL of nanogel concentration. The resultant blood fibril clots by TF-Nanogels showed thicker fibrin networks than those by free tTF-pHLIPs in SEM pictures (400 nm vs. 60 nm of fibrin diameters), suggesting the interpenetrating networks of fibril clots, platelets/ hemocytes and PIB nanogels. Compared to i.v. injection of tTF-pHLIPs, TF-Nanogels exihited an long-term vascular occlusion in VX2 tumor-bearing rabbits only at a half dose (250 μg) of i.v. injection, indicating the synergistic antitumor efficacy between PIB nanogels and tTF-pHLIPs. TF-Nanogels showed favorable supression on tumor angiogenesis and metastasis due to far lower levels of HIF-1α, VEGFs and MMP-9 than tTF-pHLIPs, and distinct antitumor immune response (higher levels of CD3 + and CD8 + T cells). TF-Nanogels were promising embolic agents to enhance TAE antitumor efficacy (angiogenesis inhibition, metastasis inhibition, antitumor immune activation, etc. ) by the synergistic effect between coagulative artery infraction of tTF-pHLIPs and temperature sensitive artery embolization of PIB nanogels in interventional therapies on hepatocellular carcinoma.

High sensitive sol-gel based electrochemical immunosensor for Clenbuterol Determination

High sensitive sol-gel based electrochemical immunosensor for Clenbuterol Determination

Pickering gel emulsion of lipiodol stabilized by hairy nanogels for intra-artery embolization antitumor therapy

Lipiodol has been widely used in clinical interventional therapy on hepatocellular cancer (HCC). It remains a huge challenge for Lipiodol to maintain in vivo stability, flowability and long-term artery embolization. Here, Hairy Poly (N-isopropylacrylamide-co-acrylic acid) (hPNA) nanogels were synthesized for stabilizing a temperature sensitive Pickering gel emulsion of Lipiodol. The emulsion exhibited temperature sensitive sol-gel transition with high thermodynamic stability, and exhibited high yield stress in gel phase, but favorable flowability and shearing-thinning property in sol phase. In vivo artery embolization corroborated that the Pickering gel emulsion could achieve long-term X-ray imaging and complete embolization, leading to the enhancement of antitumor effect by depleting expression of VEGF and CD31. The Pickering gel emulsion is promising to be developed as a novel embolic material for TAE therapy.

Hydroxybutyl Chitosan Centered Biocomposites for Potential Curative Applications: A Critical Review.

Chitosan (CS), a natural biopolymer, has been extensively explored for multiple applications including tissue engineering, gene therapy, bioimaging, and sewage treatment due to its abundant availability, intrinsic biocompatibility, biodegradability, and tunable biological properties. Nevertheless, the actual use of CS is limited because of its water-insolubility in physiological circumstances, which could be optimized by chemical modifications via active side groups. Etherification is one of the most widely used reactions to obtain water-soluble CS derivatives, such as hydroxybutyl CS (HBC). HBC, synthesized by grafting hydroxybutyl groups to the functional hydroxyl and amino groups of CS skeleton, has been demonstrated to possess superior biological properties over those of CS, especially satisfactory water solubility in neutral condition and reversible stimulus-response against external heat. Meanwhile, the unique characteristics of thermally sensitive "sol-gel" and "sol-micelle" transition have gained tremendous attention, which differ in heterogeneously and homogeneously synthesized HBC. Herein, we discuss the synthesis (heterogeneously and homogeneously) of HBC, favorable physiochemical properties of HBC, and HBC-centered biocomposites in a range of formulations or dosage forms such as sponges, gels, nanoparticles, nanofibers, and films. Meanwhile, we summarize the potential bioapplications and trends of HBC and HBC centered biocomposites and offer our perspectives on the plausible advances in this field in the near future.

In vitro and in vivo evaluation of 3D biodegradable thermo/pH sensitive sol-gel reversible hydroxybutyl chitosan hydrogel.

Hydrogels have been widely utilized in various fields as a function of their tunable physical and biochemical properties. The unique physical properties of hydrogels, including their porosity and swelling capacity, make them favorable platforms for drug delivery. Although chitosan is the most popular natural polymer due to its biocompatibility, low toxicity, biodegradability, and other biofunctional activities, its potential commercial applications are constrained due to its poor solubility in water. Hydroxybutyl chitosan (HBCS) was synthesized in our study to improve its solubility. The HBCS hydrogel exhibited excellent thermo/pH sensitive sol-gel reversibility behavior from 4 °C to the gelation temperature. Additionally, the gelation time and temperature could be optimized by adjusting the HBCS concentration, gelation temperature, and pH value according to clinical requirements. The HBCS hydrogel had both favorable water-solubility and swellability when compared with unmodified chitosan. Moreover, the HBCS demonstrated lower hemolysis at a concentration of 1 mg/mL. The HBCS hydrogel was completely biodegraded after 8 weeks of muscle implantation and 7 weeks of subcutaneous implantation. These results demonstrated that the HBCS hydrogel with biodegradable thermo/pH sensitive sol-gel reversible properties had excellent cytocompatibility, histocompatibility, and biocompatibility as a drug carrier. As such, HBCS holds great promise for future biomedical applications.

ABA-type triblock copolymer micellar system with lower critical solution temperature-type sol-gel transition

A temperature sensitive sol-gel transition induced by the self-assembly of amphiphilic copolymers and its application in industry have been the objects of increasing study. We demonstrate here a two-step, reversible addition-fragmentation chain transfer (RAFT) polymerization of an ABA-type copolymer consisting of poly(N,N-dimethylacrylamide)-b-poly(diacetone acrylamide)-b-poly(N,N-dimethylacrylamide) (PDMAA-b-PDAAM-b-PDMAA). This copolymer can be easily dispersed in water, and this dispersion is critical for its lower critical solution temperature (LCST)-type sol-gel transition, which was monitored using dynamic light scattering (DLS), transmission electron microscopy (TEM), and rheology analysis, in addition to temperature-dependent 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy (FTIR). Results revealed an abnormal sphere-to-worm micellar transition of this ABA copolymer at the LCST point, which could be affected by the length of the PDAAM block (B-block), the length as well as the distribution of the PDMAA block (A-block), and the concentration of the copolymer dispersion. Thus, copolymer dispersion could be feasibly used for drug loading at a low temperature, which could then be transformed into a gel at an elevated temperature. The loading and controllable release of the model drug of paracetamol into and out of a copolymer gel was further determined. The sustained release behavior was also studied using the Rigter-Peppas model.

Temperature sensitive p(N-isopropylacrylamide-co-acrylic acid) modified gold nanoparticles for trans-arterial embolization and angiography.

Temperature sensitive p(N-isopropylacrylamide-co-acrylic acid) modified gold nanoparticles (GNP@PNA) were prepared via coordination bonding between gold and sulfur elements. Their diameter and zeta potential were 86 nm and -26.2 mV at 25 °C, and 47 nm and -30.5 mV at 37 °C respectively. Thermogravimetric characterization of GNP@PNA indicated that the PNA shell and the GNP core accounted for 19.2 wt% and 78.2 wt%, namely ca. 70-80 chains of PNA were combined on the surface of one GNP nanoparticle. GNP@PNA showed much better X-ray attenuation ability, ca. 1.6-3.3 times higher than that of Omnipaque. In addition, the temperature sensitive sol-gel transition of GNP@PNA dispersions could realize the so-called "in situ casting" embolization from tumoral aorta to peripheral arteries, and improve their angiographic ability owing to the inhibition against GNP aggregation via gelation. Renal artery embolization on normal rabbits and TAE on VX2 tumor-bearing rabbits indicated that GNP@PNA achieved better embolization for longer times than Ivalon and Lipiodol. Excellent biocompatibility of GNP@PNA dispersions was also observed via the evaluation of cytotoxicity, hemolysis and hepatorenal function.

Formulation and Evaluation of Sol-Gel Drug Delivery System for Intracanal pH Sensitive Controlled Delivery of Chlorhexidine.

Persistence of viable micro-organisms even after thorough chemomechanical debridement has been cited as a major cause for endodontic failure. Chlorhexidine is a drug, which has shown marked efficacy against Enterococcus faecalis and Candida spp., which are mostly accounted for endodontic failure and it has demonstrated high degree of substantivity to dentin by adsorption. Another issue with chlorhexidine and other intracanal medicaments is the excessive or premature peaking of the drug leading to possible side effects. The objective of this experimental work undertaken was to formulate a pH sensitive sol-gel sustained drug delivery system containing chlorhexidine. The formulations were prepared using different concentrations of GELRITE® (0.1% and 0.2%) and Chlorhexidine (0.1% and 0.2%). The prepared solutions were evaluated for pharmacological properties like sterility test, viscosity, drug content, drug release characteristics, drug excipient compatible study. The drug excipient compatibility studies showed no interaction between the excipient and the active constituent. The microbial analysis showed good efficacy against the test micro-organisms and Minimum Inhibitory Concentration (MIC) values against Candida albicans (ATCC® 14053™) was observed as 4 μl/ml for both formulation containing 0.1% and 0.2% of GELRITE® Gellan (polymer). Whereas, MIC values against Enterococcus faecalis was observed to be 3.2 μl/ml and 6 μl/ml for formulation containing 0.1% and 0.2% of GELRITE® Gellan (polymer) respectively. From the present study, it could be successfully demonstrated that sol-gel formulations can be simple, easy to administer mode of intracanal drug delivery system. Localized pH changes present within the canal can trigger sol-gel conversion thereby releasing the drug in sustained manner with less toxicity and side effects.

Integration of New Sol-Gel Films Into Optical Chemical Sensors

CSEM has developed new sol-gel based sensitive layers enabling the optical detection of volatiles and dissolved analytes with enhanced performances. These sol-gel films exhibit a hierarchical nanoporous structure. Dedicated optical readers have been developed to interrogate the optical signal of the sensitive sol-gel patches. Applications of this technology, focusing yet on O2, CO2, and pH detection, are illustrated with practical cases in aeronautics and environmental, health, and process monitoring.

Hybrid sol–gel thin films doped with a pH indicator: effect of organic modification on optical pH response and film surface hydrophilicity

Optical sensors for application in innovative wearable sensing systems such as textile-integrated systems and wireless sensor platforms rely on the development of low-cost multifunctional materials compatible with standard fabrication technologies. We are developing optically responsive pH sensitive sol–gel coatings for integration with a mobile wireless smart tag sensing system. For this application, we have fabricated a range of thin pH sensitive films using bromocresol green (BCG) indicator immobilised in inorganic–organic silica hybrid matrices prepared by a sol–gel method and deposited by spin-coating onto glass substrates. The surface hydrophilicity of the films were varied by using the inorganic sol–gel precursor tetraethoxysilane together with either methyltriethoxysilane, ethyltriethoxysilane, phenyltrimethoxysilane or glycidoxypropyltrimethoxysilane as organically modified sol–gel precursors, co-polymerised in different ratios. Spectral characterisation of the films was performed using visible absorption spectroscopy. The shift in absorption maxima and other spectral changes of the different matrices have been identified, and the apparent pK app values of the immobilised BCG pH indicator determined. The surface wettability properties of the films have been studied by measuring the contact angle of water, formamide and diiodomethane which has allowed the estimation of the surface free energy (SFE) using three different models: Owens–Wendt, Wu and van Oss-Chaudhury-Good. It is shown that the SFE of the hybrid films is directly related to the type and the degree of organic modification, which in turn has a significant effect on the pH response-time of these sensing films.

Coating functional sol–gel films inside horizontally-rotating cylinders by rimming flow/state

The fabrication of uniform sol–gel coatings with embedded functional nanomaterials inside cylinders requires detailed understanding of the gelation behavior. For sol–gel systems the viscosity is a function of gelation time that affects sol–gel coatings on the inside of a slowly, horizontally rotating cylinder. Therefore the angular velocity has to be adjusted to this time dependence. The higher the viscosity the more liquid is dragged along with the moving cylinder wall while the balance of gravity and drag limits the layer thickness. In addition, inertial forces and surface tension can create instabilities within the coated layer. Here, we show that it is important to suppress these instabilities by transitioning the viscous sol directly to a velocity that allows for the formation of an almost uniform layer. In this regime, which is the so-called rimming state, the recirculation of the gel precursor solution is strongly reduced which allows to fabricate coatings with shear sensitive sol–gel chemistries. Here, we tested this approach with 4 different aerogel systems, with low-density CH-based-, TiO2-, SiO2- and Fe2O3-aerogels, that represent a wide variety of different sol–gel behaviors. We show that the required rotational velocities for these aerogel systems can be predicted with a simple analytical approximation, and we performed computational fluid dynamics simulations to predict local shear and thickness uniformity.

Hybrid solgel Bragg grating loaded waveguide by soft-lithography and its potential use as optical sensor

Preliminary tests on the sensibility to external environment of an optical waveguide filter operating in the near infrared region are reported. Device consists of a hybrid sol-gel based grating loaded channel waveguide. Several techniques were implemented to obtain the final device. A hard master with gratings produced by Electron Beam Lithography was employed to fabricate a transparent soft mold. UV-nanoimprinting technique, exploiting the soft stamp, was used to reproduce on the hybrid photo- sensitive sol-gel film the planar grating. Optical lithogra- phy was finally applied to manufacture the grating loaded channel waveguide which is our final integrated sensor. The device was optically characterized by transmission measurements in the range 1,450-1,590 nm and its sensi- bility to external environment was tested in air and water.

Boehmite filled hybrid sol–gel system as directly writable hard etching mask for pattern transfer

We discuss some preliminary results on the development of a new kind of positive tone resist whose peculiarity is an extreme dry etch resistance. This profitable property is obtained by loading and compatibilizing with ceramic nano particles a radiation sensitive sol–gel silica based hybrid organic/inorganic system. With an appropriate choice of the nano particles, the investigated approach is suitable to be adapted and optimized for achieving high selectivity in plasma etching processes of different materials. Here, we specifically demonstrate how the filling with boehmite nano particles (aluminum hydroxide, y-AlO(OH)) confers a much higher selectivity (>60) to the radiation sensitive silica based system when used for the etching of silicon, that show a selectivity <2 if unloaded. The patterning of the new resist was carried out by X-ray lithography while the dry etching tests were made with a fluorine-based chemistry.

The role of photoinitiator and chelating agent in the fabrication of optical waveguides from UV-photocurable organo-mineral sol–gel materials

This work focuses on the role of photoinitiators and chelating agents in waveguide fabrication based on UV sensitive sol–gel materials. The key role that a photoinitiator plays in waveguide formation has been shown through examination of waveguide width and cross-sectional shape. Waveguides fabricated using Irgacure-907 were found to be on average 2.5 times wider at the top surface than those fabricated using Irgacure-819 or -1800. UV–Vis measurements on the photoinitiators confirmed that Irgacure-907 is approximately 35 times more absorbing than the other photoinitiators at the UV exposure wavelength of 325 nm. This has been found to give rise to a highly trapezoidal waveguide shape which, also affects waveguide adhesion. The influence of the chelating agent within the hybrid sol has also been studied with reference to waveguide width. These experiments clearly showed that the Zr(OPr) 4 molecule plays an active role in the photopolymerization process, and its activity is controlled by its degree of chelation. Two different chelating agents, methacrylic acid (MAAH) and isobutyric acid (IBA) were compared. The trend for both chelating agents was the same, but IBA chelated sols resulted in narrower waveguides. This has been attributed to the higher steric hindrance of IBA compared to MAAH, which would inhibit the propagation of polymerization in the coating.

Novel pH and temperature-sensitive block copolymers: Poly(ethylene glycol)-b-poly(ε-caprolactone)-b-poly(β-amino ester)

Block copolymers, composed of MPEG, PCLA and PAE, were synthesized through a combination of ring opening reaction and Michael reaction. Their aqueous solutions show a sensitive sol-gel transition by pH and temperature within a small pH range. The sol-gel phase diagrams of the block copolymer solutions were controlled deliberately by altering either the ratio of hydrophobic to hydrophilic blocks within the block copolymer or the PEG length. The aqueous block copolymer solution composed of MPEG=5,000, PEG/PCL ratio=1/0.3 and PAE=847 had a gel region including thein vivo conditions (37°C, pH 7.4). This polymer solution could be formulated with various drugs at pH 5∼6 buffer solution for the injection to the human body. This could be one of the candidate of the injectable hydrogel for the sustained release of drug.

Sol–Gel Chemistry for Ba2+ Sensors to Allow Oil Production Engineered Nanometrically

Work on the development of a Ba2 +-sensitive sol–gel based optical fiber (OF) for use in oil wells is described. The optical fiber (OF) has on its surface a Ba2 + chelating ligand (L) immobilized at a 2–16 wt% loading immobilized in a porous SiO2 sol–gel host. The authors report sol–gel routes to these SiO2 and L/SiO2 nanocomposites and describe their characterization by XPS, fluorescence, NMR, UV-vis and BET methods. They also report on the sol–gel coating and its selectivity to Ba2 +(aq).

Alkali treatment of dye-doped sol–gel glass films for rapid optical pH sensing

Alkaline post-fabrication treatment of dye-impregnated pH sensitive sol–gel films has been demonstrated as a means of overcoming the problem of extended response times associated with the use of such films in optical sensor systems. Hydrogen bonded silanol groups and water molecules present on the surface and within the bulk of the glass structure have been shown to be of great influence on the sensing characteristics. These may be modified in such a way as to dramatically improve response times without incurring the penalty of leaching of the sensitive dye. This procedure was demonstrated by producing bromocresol green doped glass films displaying response times of the order of a few seconds.