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Regarding safety concerns, nonviral gene delivery vehicles that have the required efficiency and safety for use in human gene therapy are being widely investigated. The aim of this study was to synthesize and evaluate a thiolated chitosan to improve the efficacy of oral gene delivery systems. Thiolated chitosan was synthesized by introducing thioglycolic acid (TGA) to chitosan via amide bond formation mediated by a carbodiimide. Based on this conjugate, nanoparticles with pDNA were generated at pH 4.0 and 5.0. Cytotoxicity of the thiolated chitosan/pDNA nanoparticles on Caco-2 cells was evaluated. The diameter of thiolated chitosan/pDNA nanoparticles was in the range of 100-200 nm. The zeta potential was determined to be 5-6 mV. Due to stability toward nucleases, the transfection rate of thiolated chitosan/pDNA nanoparticles was fivefold higher than that of unmodified chitosan/pDNA nanoparticles. Lactate dehydrogenase tests for thiolated chitosan/pDNA (pH 4.0 and 5.0) showed that (3.79 +/- 0.23)% and (2.9 +/- 0.13)% cell damage. According to these results, thiolated chitosan represents promising excipients for preparation DNA nanoparticles in nonviral gene delivery system.

This study was aimed at improving certain properties of pectin by introduction of thiol moieties on the polymer. Thiolated pectin was synthesized by covalent attachment of cysteine. Pectin-cysteine conjugate was evaluated for its ability to be degraded by pectinolytic enzyme. The toxicity profile of the thiolated polymer in Caco-2-cells, its permeation enhancing effect and its mucoadhesive and swelling properties were studied. Moreover insulin-loaded hydrogel beads of the new polymer were examined for their stability in simulated gastrointestinal conditions and their drug release profile. The new polymer displayed 892.27 +/- 68.68 micromol thiol groups immobilized per g polymer, and proved to have retained its biodegradability, upon addition of Pectinex Ultra SPL in-vitro, determined by viscosity measurements and titration method. Pectin-cysteine showed no severe toxicity in Caco-2 cells, as tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Moreover, the synthesized polymer exhibited a relative permeation enhancement ratio of 1.61 for sodium fluorescein, compared to unmodified pectin. Pectin-cysteine conjugate exhibited approximately 5-fold increased in in-vitro adhesion duration and significantly improved cohesive properties. Zinc pectin-cysteine beads showed improved stability in simulated gastrointestinal media; however, insulin release from these beads followed the same profile as unmodified zinc pectinate beads. Due to favourable safety and biodegradability profile, and improved cohesive and permeation-enhancing properties, pectin-cysteine might be a promising excipient in various transmucosal drug delivery systems.

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Pectinate (PEC) beads are multiparticulate dosage forms which have been extensively investigated for oral drug delivery; however their mucoadhesive properties in various sections of GI tract have, not been yet reported. This work evaluated the in vitro mucoadhesive properties of PEC bead formulations, on rat everted gastrointestinal sections, either with or without trimethyl chitosan (TMC), an absorption-enhancing and fairly mucoadhesive derivative of chitosan. Reference Carbomer 934P (C934P) granules, as an established mucoadhesive polymer, and ethyl cellulose (EC)-coated pellets, as a nonmucoadhesive dosage form, were also used for comparison. Water uptake studies were also performed to further explain the effect of hydration on mucoadhesive properties. PEC beads showed mucoadhesion, which was in some cases comparable to C934P granules, towards the gastrointestinal tissues with following ranking: duodenum approximately jejunum approximately ileum > cecum > colon > stomach. In the dry state, the beads containing TMC were more mucoadhesive, while in the moist state simple PEC beads were shown to be more mucoadhesive. Over-hydration of TMC-containing beads may account for this observation. The results of this study suggest that in cases which prehydration can be avoided, such as when the beads are protected in a site-specific oral capsule, prior to reaching the target tissue, the incorporation of TMC into beads might be useful, as a means of increasing the mucoadhesive properties; However, further studies are needed to clarify their in vivo feasibility.

The most critical point in pharmacotherapy of OCD is the need for the high-dose and long-term use of drugs. In OCD, generally the higher doses of applicable drugs than those used in depression are required, often exceeding the recommended maximum dose. Moreover, such high doses should be given for at least 10 - 12 weeks to ensure the adequate treatment duration for the clinical effects to emerge. This long-term high-dose maintenance therapy increases the risk of drug toxicity and adverse effects. Physicians should take extra care in periodical assessment of signs and symptoms of metabolic and toxicological complications in patients. Subjective symptoms reported by patients should be carefully assessed and not attributed to obsessive nature of the patients.