Thiolated Chitosans: Novel Polymers for Mucoadhesive Drug Delivery – A Review

Chitosan is a natural polycationic copolymer consisting of glucosamine and N-acetylglucosamine units. The polymer has valuable properties as a biomaterial because it is considered to be biocompatible, biodegradable and non-toxic. The purpose of this review article is to provide detailed information about thiolated chitosans which are gaining popularity because of their high mucoadhsiveness and extended drug release properties. The derivatization of the primary amino groups of chitosan with coupling reagents bearing thiol functions leads to the formation of thiolated chitosans. Various properties of chitosan are improved by the immobilization of thiol groups. Due to the formation of disulfide bonds with mucus glycoproteins, mucoadhesiveness is augmented. The permeation of paracellular markers through mucosa can be enhanced by utilizing thiolated instead of unmodified chitosan. Moreover, thiolated chitosans display in situ gelling features due to the pH-dependent formation of inter- as well as intra-molecular disulfide bonds. This latter process provides, strong cohesion and stability of carrier matrices, being based on thiolated chitosans. The in situ gel formation within the pH range of 5 to 6.8 makes the application of thiolated chitosans on vaginal, nasal and ocular mucosa also possible. Thiolated chitosans can guarantee prolonged controlled release of embedded therapeutic ingredients. Keywords: Thiolated chitosan,Thiomers, Mucoadhesion, Permeation enhancement, In situ gelation Tropical Journal of Pharmaceutical Research Vol. 7 (3) 2008: pp. 1077-108

Pharmacological effects of aqueous–ethanolic extract of Hibiscus rosasinensis on volume and acidity of stimulated gastric secretion

ObjectiveTo explore the effects of extract of Hibiscus rosasinensis (H. rosasinensis) on the volume, free and total acidity of gastric secretion induced by carbachol.MethodsAnimals were kept on fasting for 48 h, then the pylorus of each animal was ligated. They were randomly divided into 5 groups and treated by carbachol at 600 μg/kg. Then animals in group II – V were treated by H. rosasinensis extract at 250 and 500 mg/kg body weight, cimetidine at 2.5 mg/kg and verapamil at 10 mg/kg body weight intraperitoneally, respectively. The volume, free and total acidity of gastric secretion were observed and compared.ResultsIt was found that the extract significantly reduced the volume, free and total acidity of gastric secretion (P<0.01). These reductions were comparable to cimetidine and verapamil. And the reduction in the volume and free acidity were more significant in cimetidine and verapamil treated group indicating that cimetidine and verapamil were more effective.ConclusionsThe extract of H. rosasinensis can reduced the volume, free and total acidity of gastric secretion, and can be used effectively in the treatment of peptic ulcer

Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan

Purpose: Poly (L-lactic acid) (PLA) microparticles encapsulating Hepatitis B surface antigen (HBsAg) with alum and chitosan were investigated for their potential as a vaccine delivery system. Methods: The microparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method with polyvinyl alcohol (PVA) or chitosan as the external phase stabilising agent showed a significant increase in the encapsulation efficiency of the antigen. Results: PLA-Alum and PLA-chitosan microparticles induced HBsAg serum specific IgG antibody responses significantly higher than PLA only microparticles and free antigen following subcutaneous administration. Chitosan not only imparted a positive charge to the surface of the microparticles but was also able to increase the serum specific IgG antibody responses significantly. Conclusions: The cytokine assays showed that the serum IgG antibody response induced is different according to the formulation, indicated by the differential levels of interleukin 4 (IL-4), interleukin 6 (IL-6) and interferon gamma (IFN-γ). The microparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-4, IL-6 and IFN-γ

Functionalized Calcium Carbonate as a Novel Pharmaceutical Excipient for the Preparation of Orally Dispersible Tablets

PURPOSE: To overcome the limitation of insufficient hardness during the production of rapidly disintegrating orally dispersible tablets (ODTs). Furthermore, we investigated the properties and usefulness of functionalized calcium carbonate (FCC) as a new pharmaceutical excipient for the production of ODTs. METHODS: A highly sensitive tensiometer-based method was developed to measure kinetics of weight loss during tablet disintegration. With this method we were able to determine the residence time of tablets placed on a basket immersed into a test medium. The shapes of tensiometer plots allowed us to categorize substances into four different types of disintegration. RESULTS: At the same volume and hardness, the tablet formulations with FCC showed a significantly higher porosity (over 60%) than all other formulations. Residence time depended mainly on the tablet composition rather than on porosity. When combined with disintegrants, FCC formulations exhibited favorable disintegration properties, comparable to those of the marketed drug risperidone oro (disintegration time ca. 10 s). CONCLUSIONS: Oral dosage forms - based on the new pharmaceutical excipient FCC - can be designed to have a short disintegration time combined with good mechanical strength. Due to these properties, FCC can be used for the preparation of ODTs

MYOD-SKP2 axis boosts tumorigenesis in fusion negative rhabdomyosarcoma by preventing differentiation through p57Kip2 targeting.

Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27Kip1 and p57Kip2, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic features and prevents in vivo tumor growth. These effects are mirrored by the investigational NEDDylation inhibitor MLN4924. Results demonstrate a crucial crosstalk between transcriptional and post-translational mechanisms through the MYOD-SKP2 axis that contributes to tumorigenesis in FN-RMS. Finally, NEDDylation inhibition is identified as a potential therapeutic vulnerability in FN-RMS