Co-delivery of zinc and 5-aminosalicylic acid from alginate/N-succinyl-chitosan blend microspheres for synergistic therapy of colitis.

The present study developed novel zinc ion cross-linked alginate/N-succinyl-chitosan (NSC) blend microspheres (MS) for co-delivery of zinc and 5-aminosalicylic acid (5-ASA) for synergistic therapy of colitis. Physicochemical characterization of blend MS was assessed using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and energy dispersive X-ray spectrometer (EDS). In vitro release studies demonstrated that blend MS has a pH-dependent release property. Both 5-ASA and zinc have lower release in acid medium and higher release in colonic environment. The therapeutic efficacy of zinc cross-linked blend MS was evaluated using induced-colitis rat models, and showed a superior treatment effect in alleviating inflammation of colitis rats. No systemic toxicity was observed after oral administration of blend MS. Therefore, zinc ion cross-linked alginate/N-succinyl-chitosan blend MS appeared to be a good candidate for co-delivery of zinc and 5-ASA to colon, and had great potential application in inflammatory bowel diseases (IBD) treatment.

Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon.

In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease.

Injectable and Self-Healing Carbohydrate-Based Hydrogel for Cell Encapsulation.

With the fast development of cell therapy, there has been a shift toward the development of injectable hydrogels as cell carriers that can overcome current limitations in cell therapy. However, the hydrogels are prone to damage during use, inducing cell apoptosis. Therefore, this study was carried out to develop an injectable and self-healing hydrogel based on chondroitin sulfate multiple aldehyde (CSMA) and N-succinyl-chitosan (SC). By varying the CSMA to SC ratio, the hydrogel stiffness, water content, and kinetics of gelation could be controlled. Gelation readily occurred at physiological conditions, predominantly due to a Schiff base reaction between the aldehyde groups on CSMA and amino groups on SC. Meanwhile, because of the dynamic equilibrium of Schiff base linkage, the hydrogel was found to be self-healing. Cells encapsulated in the hydrogel remained viable and metabolically active. In addition, the hydrogel produced minimal inflammatory response when injected subcutaneously in a rat model and showed biodegradability in vivo. This work establishes an injectable and self-healing hydrogel derived from carbohydrates with potential applications as a cell carrier and in tissue engineering.

Anti-photobleaching flower-like microgels as optical nanobiosensors with high selectivity at physiological conditions for continuous glucose monitoring.

Optical glucose detection holds considerable promise for continuous in vivo glucose monitoring with wireless transdermal transmission and long-lasting activity. To construct a new class of optical glucose nanobiosensors with high sensitivity and selectivity at physiological conditions, the first generation of fluorescent poly(amido amine) (G1.0 PAMAM), serving as the optical code, was introduced into glucose-sensitive poly(N-isopropylacrylamide-(2-dimethylamino)ethyl methacrylate-3-acrylamidephenylboronic acid) copolymer microgels via a facile method. The fabricated microgels display the ability of adapting to the surrounding medium of different glucose concentrations over a clinically relevant range (0-20 mM) and convert biochemical signals into optical signals. As nanobiosensors, the G1.0 PAMAM functionalized microgels exhibit high selectivity for glucose over various kinds of potential primary interferents, such as lactate, human serum albumin and metal ions, in the physiologically important glucose concentration range. Compared to traditional fluorescent dyes and quantum dots, which are limited by photobleaching and toxicity, this microgel with remarkable anti-photobleaching property and low toxicity makes it possible to be used for long-term continuous glucose monitoring. Through in vivo investigations, it can be observed that G1.0 PAMAM functionalized microgels can achieve wireless transdermal detection, indicating that the fabricated microgels have potential applications as a new generation of nanobiosensors for the highly sensitive and minimally invasive continuous glucose monitoring.

Fluorescent and thermoresponsive supramolecular systems: synthesis, self-assembly and application in percutaneous optical monitoring.

Supramolecular systems were constructed by the non-covalent coupling between PAMAM dendrimers with adamantyl groups and ß-cyclodextrin graft PNIPAAm through host-guest interactions. Such supramolecular systems can further self-assemble into nanorods, which have thermoresponsive and excellent fluorescence properties. The injectable and percutaneous detection of fluorescent supramolecular systems will be of significant advantage in the future of biomedical monitoring.

The impact of drug transporters on adverse drug reaction.

In this review, we have highlighted the adverse drug reaction mediated by transporters from two aspects: (1) competitive interactions between drug and drug/metabolite/endogenous substance mediated by transporters; (2) the expression/function change of transporter due to physiologic factors, disease, and drugs induction. It indicated that transporters exhibited a broad substrate specificity with a degree of overlap, which could change the pharmacokinetics of drugs and cause toxicity due to competition interactions among substrates. In addition, the expression and function of transporters were regulated by physiological conditions, pathological conditions, and drugs induction, which could cause adverse drug reaction and interindividual differences. Furthermore, one substrate was always medicated by several transporters and often subjected to metabolism by CYP enzymes, so we should be more aware of the increased plasma concentration of drugs caused by drug transporters as well as drug metabolizing enzymes synergistically, especially for drugs with narrow therapeutic window. In addition, the weightiness for one transporter to induce drugs plasma/tissue concentration change could be different in different condition. On the whole, transporters were corresponding with systemic/organs exposure of drug/metabolites/endogenous compounds. So understanding the expression and function in drug transporters will result in better strategies for optimal dosage regimen and reduce the risk for drug adverse reaction as well as adverse drug-drug interactions.

Effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid in rats.

Pyridoxine is always simultaneously administered orally with isoniazid for tuberculosis patients in the clinic to prevent or treat the nervous system side effects induced by isoniazid. So the aim of this research was to investigate the effects of pyridoxine on the intestinal absorption and pharmacokinetics of isoniazid. The intestinal absorption of isoniazid with or without pyridoxine was investigated by the rat single-pass intestinal perfusion model in situ, and a high-performance liquid chromatographic method was applied to study the pharmacokinetics of isoniazid with or without pyridoxine. The results suggested that the intestinal apparent permeability (P app) and intestinal absorption rate constant (K a) for isoniazid (30 µg/ml) were decreased by 43.7 and 36.4 %, respectively, by co-perfused pyridoxine (40 µg/ml). In vivo, the effect of pyridoxine on isoniazid pharmacokinetic correlated with the doses of pyridoxine. The blood concentrations of isoniazid at the absorption phase were affected by co-administered pyridoxine, but the AUC and C max of isoniazid were not greatly affected by pyridoxine as expected from the inhibition by pyridoxine of the intestinal absorption of isoniazid, which could be caused by its rapid absorption phase. Therefore, although the intestinal absorption of isoniazid could be significantly inhibited by pyridoxine, the pharmacokinetics of isoniazid oral administration was not greatly affected by the decreased intestinal absorption of isoniazid due to its rapid absorption.

An integrated simultaneous distillation-extraction apparatus for the extraction of essential oils from herb materials and its application in Flos Magnoliae.

A large number of herb materials contain essential oils with extensive bioactivities. In this work, an integrated simultaneous distillation-extraction (ISDE) apparatus was developed. To demonstrate its feasibility, the performance of ISDE was evaluated for the extraction of essential oil from Flos Magnoliae and compared with conventional techniques including steam distillation (SD) and simultaneous distillation-extraction (SDE). According to the product yield, the time consumed and the composition of oil, the essential oils isolated by ISDE were better than that obtained by SD and similar to those obtained by SDE. ISDE was also better than SDE due to its simple operation and lower consumption of energy and organic solvent.

[Effects of Yuquan pills on pharmacokinetics of metformin hydrochloride in diabetic rats].

OBJECTIVE: To study effects of Yuquan pills on the pharmacokinetics process of metformin hydrochloride in diabetic rats. METHOD: After administration Yuquan pills 7 day to the diabetic rats, the metformin hydrochloride was orally administrated, then the blood samples were collected at different time. The concentrations of metformin hydrochloride in plasma were determined by HPLC method and the pharmacokinetic parameters were calculated. RESULT: The pharmacokinetic parameter Cmax of the controlling group and the testing group were respectively, 18.95, 21.76 mg x L(-1); t1/2 were 1,069.8, 1,767.4 min, respectively; CL/F were 0.013, 0.008 L x min(-1) x kg(-1); AUC were 10,042.1, 10,712.2 mg z L(-1) x min(-1) respectively. CONCLUSION: The pharmacokinetics process of metformin hydrochloride in diabetic rats fits one-compartment model. Yuquan pills has a significant effect on the pharmacokinetics of metformin hydrochloride in diabetic rats.