Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Methylated N-(4-N,N-Dimethylaminobenzyl) Chitosan, a Novel Chitosan Derivative, Enhances Paracellular Permeability Across Intestinal Epithelial Cells (Caco-2)

The aim of this study was to investigate the effect of methylated N-(4-N,N-dimethylaminobenzyl) chitosan, TM-Bz-CS, on the paracellular permeability of Caco-2 cell monolayers and its toxicity towards the cell lines. The factors affecting epithelial permeability, e.g., degree of quaternization (DQ) and extent of dimethylaminobenzyl substitution (ES), were evaluated in intestinal cell monolayers of Caco-2 cells using the transepithelial electrical resistance and permeability of Caco-2 cell monolayers, with fluorescein isothiocyanate dextran 4,400 (FD-4) as a model compound for paracellular tight-junction transport. Cytotoxicity was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide viability assay. The results revealed that, at pH 7.4, TM-Bz-CS appeared to increase cell permeability in a concentration-dependent manner, and this effect was relatively reversible at lower doses of 0.05–0.5 mM. Higher DQ and the ES caused the permeability of FD-4 to be higher. The cytotoxicity of TM-Bz-CS depended on concentration, %DQ, and %ES. These studies demonstrated that this novel modified chitosan has potential as an absorption enhancer

Synthesis and characterization of water-soluble dendronized chitosan using newkome-type dendrons

With increasing emphasis on environmental care 7 and use of renewable resources, simple and effective dendroniza- 8 tion processes were performed to obtain chitosan derivatives. We 9 present different alternatives for the modification of chitosan: 10 dendronization with a biocompatible dendron; a quaternization 11 process with an ammonium salt, which confers a permanent 12 positive charge to the polymer; and a combination of method- 13 ologies allowing amphiphilic polymers. This process confers 14 unique multivalent properties to the native chitosan, and further 15 modifications reach multivalent water-soluble polymers. Hence, 16 the most important highlight of this work is the use of renewable 17 natural polymers and the different methodologies applied to nontoxic solvents with low temperatures. The process described in 18 this paper represents a sustainable alternative for obtaining a functionalized material with properties suitable for application in 19 different areas, such as biomedicine or environmental remediation.Fil: Rimondino, Guido Noé. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Strumia, Miriam Cristina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Martinelli, Marisa. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin