Nanofibers as precursors for the rapid formation of hydrogels.

Hydrogels can be used in surgeries, which require a support material to maintain the correct anatomy. One major limitation is however the time required for the preparation of hydrogels under urgent conditions. Herein, we report a new method for a very fast preparation of hydrogels at room temperature. Nanofibers of dextran containing vinyl groups produced by electrospinning are loaded with redox- or photo-initiators for radical polymerization. Once dissolved in water, the nanofibers yield hydrogels either spontaneously or upon irradiation with UV light. We also show that the nanofibers can be loaded with active fillers so that hydrogels embedding nanocapsules are obtained. This concept could be applied for the rapid preparation of functional hydrogels which are needed as implants.

Marrying the incompatible for better: Incorporation of hydrophobic payloads in superhydrophilic hydrogels.

HYPOTHESIS: The entrapment of lyophobic in superhydrophilic hydrogels is challenging because of the intrinsic incompatibility between hydrophobic and hydrophilic molecules. To achieve such entrapment without affecting the hydrogel's formation, the electrospinning of nanodroplets or nanoparticles with a water-soluble polymer could reduce the incompatibility through the reduction of interfacial tension and the formation of a barrier film preventing coalescence or aggregation. EXPERIMENTS: Nanodroplets or nanoparticles dispersion are electrospun in the presence of a hydrophilic polymer in hydrogel precursors. The dissolution of the hydrophilic nanofibers during electrospinning allows a redispersion of emulsion droplets and nanoparticles in the hydrogel's matrix. FINDINGS: Superhydrophilic hydrogels with well-distributed hydrophobic nanodroplets or nanoparticles are obtained without detrimentally imparting the viscosity of hydrogel's precursors and the mechanical properties of the hydrogels. Compared with the incorporation of droplets without electrospinning, higher loadings of hydrophobic payload are achieved without premature leakage. This concept can be used to entrap hydrophobic agrochemicals, drugs, or antibacterial agents in simple hydrogels formulation.

Nanocapsules with excellent biocompatibility and stability in protein solutions.

Silica nanocapsules (SiO2NCs) are usually prepared with cationic surfactants that are not cytocompatible. Dialysis can be used to remove surfactants but leads to instability of the SiO2NCs when they are in the presence of proteins or biological media. Herein, SiO2NCs stabilized with a reactive surfactant are synthesized to prevent leaching upon dialysis. The SiO2NCs show superior stability and biocompatibility compared with SiO2NCs prepared with conventional surfactants. The SiO2NCs can be used in self-healing materials, smart agriculture and biomedical applications.

Halochromic Polymer Nanosensors for Simple Visual Detection of Local pH in Coatings.

Replacing metallic structures before critical damage is beneficial for safety and for saving energy and resources. One simple approach consists in visually monitoring the early stage of corrosion, and related change of pH, of coated metals. We prepare smart nanoparticle additives for coatings which act as a pH sensor. The nanoparticles are formed with a terpolymer containing two dyes as side chains, acting as donor and acceptor for a FRET process. Real time monitoring of the extent of localized corrosion on metallic structures is then carried out with a smartphone camera. Colored pH mapping can be then manually retrieved by an operator or automatically recorded by a surveillance camera.

Inflammation-responsive nanocapsules for the dual-release of antibacterial drugs.

Herein, we design inflammation-responsive nanocapsules containing two antibiotics. The releases are programmed to be triggered under conditions occurring at the different stages of wound healing. The nanocapsules exhibit excellent antibacterial activities against Gram-positive, Gram-negative, and antibiotic-resistant bacteria. Incorporation of small amounts of nanocapsules in hydrogels leads to efficient antibacterial wound dressings.

Emulsion Techniques for the Production of Pharmacological Nanoparticles.

Nanoparticles have the advantages over micron-sized particles to typically provide higher intracellular uptake and drug bioavailability. Emulsion techniques are commonly used methods for producing nanoparticles aiming at high encapsulation efficiency, high stability, and low toxicity. Here, the recent developments of nanoparticles prepared from emulsions, the synthesis of nanoparticles, their physicochemical properties, and their biomedical applications are discussed. Selection of techniques, such as emulsion polymerization, miniemulsion polymerization, microemulsion polymerization, and emulsion-solvent evaporation processes, strongly influences morphologies, size distributions, and particle properties. Details in the synthetic strategies governing the performance of nanoparticles in bioimaging, biosensing, and drug delivery are presented. Benefits and limitations of molecular imaging techniques are also discussed.

Study of biodistribution and systemic toxicity of glucose functionalized SPIO/DOX micelles.

The present study examined the cytotoxicity and magnetic resonance imaging (MRI) distribution of cancer-targeted, MRI-visible polymeric micelles that encapsulate doxorubicin (DOX) and superparamagnetic iron oxide (SPIO) and are conjugated with glucose as a targeting ligand. In this study, the micelles were investigated the clinical potential of glucose-micelles, in vitro cytotoxicity assays of nonencapsulating or SPIO-and-DOX-coencapsulating micelles were performed on L929 mouse fibroblasts, and we found that glucose-micelles did not exert in vitro cytotoxic effects. Next, in vitro MRI detectability of glucose SPIO micelles was evaluated at the loaded SPIO content of 2.5% and 50%, and it was found that glucose-micelles can increase MRI relaxivity (r2*) at high SPIO loading. Furthermore, 50% SPIO micelles persisted in the blood circulation for up to 5 days (slow liver clearance) as determined by in vivo MRI. For in vivo toxicity evaluation, 50% SPIO/DOX micelles at a dose up to 18 (mg DOX)/(kg body weight) showed no impact on animal health according to clinical chemistry and clinical hematology laboratory testing. Altogether, these results indicate that glucose-micelles can serve as an effective and safe drug delivery system.

pH-Responsive Nanofibers for Precise and Sequential Delivery of Multiple Payloads.

Effective combination therapies can be achieved by programming materials for controlling release sequence, timing, and dose of multiple payloads. Herein, we synthesize dextran esters by coesterification of dextran, which display responsive properties at a precise pH threshold between 5.0 and 7.0. Multilayers electrospun nanofibers are prepared so that three different payloads are entrapped in three different dextran esters. The release of the three drugs can be sequentially and independently activated by a gradual increase of pH value. Because both pH threshold and release kinetics are matching conditions encountered by aliments along the gastrointestinal tract, these dextran ester multilayer nanofibers are promising for oral drug delivery.

Glucose-installed biodegradable polymeric micelles for cancer-targeted drug delivery system: synthesis, characterization and in vitro evaluation.

Glucose metabolism of cancer can be used as a strategy to target cancer cells which exhibit altered glycolytic rate. The facilitated glucose transporter (Glut) plays an important role in enhancement glycolytic rate resulting in increased glucose uptake into cancer cells. 18FGD-PET image is an example for using Glut as a targeting to diagnose the high glycolytic rate of tumor. Thus, Glut may be adapted to target cancer cells for drug delivery system. Herein, biodegradation polymeric micelles target cancer cells by Glut was fabricated. The amphiphilic block copolymer of poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) was synthesized where terminal group of the PEG chain was installed with glucose molecules. The 1H-NMR confirmed the existence of glucose moiety from two distinct peaks (5.2 and 4.7 ppm) of protons at anomeric carbon of glucose. Glucose-PEG-b-PCL spontaneously forms micelles in an aqueous solution. The size and zeta potential were 22 nm and -7 mv, respectively. Glucose-micelles have high stability, and no evidence of cytotoxicity was found after incubation for 7 days. Doxorubicin, used as a fluorescent probe, was loaded into glucose-micelles. The enhanced amount of doxorubicin as a result of glucose-micelles in PC-3, MCF-7 and HepG2 was evaluated by fluorescence microscopy and flow cytometer. Glucose molecules on the surface of micelles increased internalization and enhanced uptake of micelles via bypassing endocytosis pathway. These results show the use of glucose as a targeting ligand on the micelle surface to target cancer cells via Glut.

Solubility enhancement and in vitro evaluation of PEG-b-PLA micelles as nanocarrier of semi-synthetic andrographolide analogue for cholangiocarcinoma chemotherapy.

BACKGROUND: Semi-synthetic andrographolide analogue (19-triphenylmethyl ether andrographolide, AG 050) is a C-19 substituted andrographolide which is the major constituent from Andrographis Paniculata Nees (Acanthaceae). The analogue has previously been reported to be highly cytotoxic against several cancer cell lines. Nevertheless, its poor water solubility limits clinical applications of this compound. OBJECTIVES: To improve the aqueous solubility and bioavailability of AG 050 by protonation and encapsulation in poly(ethylene glycol)-b-poly(d,l-lactide) (PEG-b-PLA) polymeric micelles. MATERIALS AND METHODS: PEG-b-PLA micelle was employed as a nanocarrier for AG 050. The physicochemical properties and in vitro cytotoxicity against cholangiocarcinoma (CCA) (KKU-M213) cell line were done in this study. RESULT AND DISCUSSION: Hydrochloride salt of AG 050 (AG 050-P) greatly enhanced the solubility of this compound (15-fold). PEG-b-PLA was able to encapsulate AG 050-P in hydrophobic core with a significant increase in the amount of AG 050-P in aqueous solution (280-fold). Film sonication method provided greater results in drug-loading study as compared to micelles via solvent evaporation. In addition, the encapsulated AG 050-P exhibited sustained release pattern and excellent cytotoxicity activity against KKU-M213 with IC50 of 3.33 µM. CONCLUSION: Nanoencapsulation of AG 050-P implicated its potential development for clinical use in CCA treatment.

Comparative studies of poly(ε-caprolactone) and poly(D,L-lactide) as core materials of polymeric micelles.

Polymeric micelles have been successfully used to deliver a variety of therapeutic agents. Nonetheless, several limitations and considerations must be clarified and well-studied to achieve the highest therapeutic effect. In this study, a series of methoxy poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) and methoxy poly(ethylene glycol)-block-poly(D,L-lactide) (PEG-b-PLA) with varying molecular weight (MW) of hydrophobic core segment were synthesized. These block copolymers can form micelle with PCL or PLA as core-forming blocks and PEG as a coronal material. The effect of MW on micelle size and critical micelle concentration (CMC) was studied. DOX (DOX) was encapsulated inside the micelle core. Drug-loading content and size of micelles were studied. Drug release studies inside cells were evaluated by confocal laser scanning microscopy. In summary, the PLA core which is less hydrophobic than PCL showed higher CMC, smaller micelle size and faster DOX release inside nucleus.

PEG-b-PCL and PEG-b-PLA polymeric micelles as nanocarrieres for lamellarin N delivery.

Lamellarin N (Lam N) is a member of an interesting marine natural product class isolated from mollusks and subsequently found in ascidians and sponges. The limited aqueous solubility of Lam N hinders further studies on its cytotoxic activity against cancer cells. In this study, micelles comprising poly(ethylene glycol)-block-poly(ε-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-block-poly(D, L-lactide) (PEG-b-PLA) were developed to circumvent Lam N limited aqueous solubility. The results showed that an increase in the molecular weight of both core materials resulted in higher Lam N loading content, whereas the release of Lam N decreased as a function of molecular weight of PCL and PLA. With less hydrophobic property, PLA micelles provided faster Lam N release. Thus, polymeric micelles could be utilized as controlled-release delivery systems for poorly water soluble Lam N.

Pughiinin A, a sesquiterpene from the fungus Kionochaeta pughii BCC 3878.

A novel secondary metabolite, pughiinin A, together with pycnidione, mevalonolactone, and 7-hydroxy-2-methylchromanone, was isolated from the seed fungus Kionochaeta pughii BCC 3878. The chemical structure was established by spectroscopic methods and by single crystal X-ray crystallography. Pughiinin A and pycnidione exhibited in vitro antiplasmodial activity against Plasmodium falciparum (K1 strain). Pycnidione also showed anti-cancer activity against KB and BC cell lines with the IC 50 values of 2.0 and 1.6 microg/mL, respectively.