Evaluation of dibutyrylchitin as new excipient for sustained drug release

Dibutyrylchitin (DBC), a lipophilic chitin diester, has been synthesized from chitin and butyric anhydride with methanesulfonic acid as catalyst. Exhaustive esterification of free alcoholic groups of chitin was assessed by FT-IR and 1H-NMR spectroscopy. High degree of alkyl substitution allowed DBC to acquire an almost completely lipophilic character. Tablets of paracetamol and metformin employing DBC as major excipient, in comparison with starch, microcrystalline cellulose, lactose and polyvinylpyrrolidone, were prepared and rates of drug release were checked by dissolution test assays. DBC released drug at a lower rate than that of the other tested materials. A comparison study of rate release of metformin from DBC tablets and from metformin-hydroxypropyl methylcellulose prolonged release oral formulation available on the market has been also curried out. Under the same conditions and in the presence of the same amount of loaded drug, DBC released 64% of metformin whereas hypromellose-based tablets released 87%

ORAC of chitosan and its derivatives

Chitosan and chitosan derivatives are receiving a lot of attention as materials of natural origin which possess radical scavengers, antioxidants and antimicrobial properties, especially in food applications. With the aim to apply the Oxygen-Radical Absorbance Capacity assay (ORAC), to detect the polysaccharides capacity to scavenge the peroxyl radical, four different grafted chitosan derivatives were synthesized.Among the synthesized derivatives, N-acetyl cysteine-g-chitosan was found to have the highest ORAC value, while gallic acid-g-chitosan and p-hydroxybenzoic acid-g-chitosan had respective 70% and 42% of ORAC values of the former. On the contrary, p-methoxybenzoic acid-g-chitosan did not show any significant difference in antioxidant activity from the unmodified chitosan. A linear correlation between ORAC values and total phenols measured with the Folin-Ciocalteau reagent was shown. The combination of ORAC and Folin-Ciocalteau assays is a useful system to monitor the growth of the acquired antioxidant capacity in relation to the type of phenolic compound used for grafting

PEGylated chitosan derivatives: synthesis, characterizations and pharmaceutical applications

This review sets out to describe and discuss the synthetic approaches and the fields of application of PEGylated chitosan copolymers especially for medical use. The PEGylation of chitosan and chitosan derivatives is able to add new physicochemical properties to the cationic polysaccharide polymers, thereby overcoming some limitations, especially regarding their solubility and their use in drug and gene delivery (DNA and siRNA). All methods of derivatization have been considered and described together with the different methods of characterization of the copolymers. The capacities of PEGylated chitosan to reduce chitosan toxicity, to enhance membrane permeation and to form thermosensitive hydrogels have also been discussed

Surface Characterisation of Bioadhesive PLGA/Chitosan Microparticles Produced by Supercritical Fluid Technology

Purpose: Novel biodegradable and mucoadhesive PLGA/chitosan microparticles with the potential for use as a controlled release gastroretentive system were manufactured using supercritical CO 2 (scCO 2) by the Particle Gas Saturated System (PGSS) technique (also called CriticalMix TM). Methods: Microparticles were produced from PLGA with the addition of mPEG and chitosan in the absence of organic solvents, surfactants and crosslinkers using the PGSS technique. Microparticle formulations were morphologically characterized by scanning electron microscope; particle size distribution was measured using laser diffraction. Microparticle surface was analyzed using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) to evaluate the presence of chitosan on the surface. Mucoadhesiveness of the microparticles was evaluated in vitro using a mucin assay employing two different kinds of mucin (Mucin type III and I-S) with different degrees of sialic acid contents, 0.5-1.5% and 9-17%, respectively. Results: The two analytical surface techniques (XPS and ToF-SIMS) demonstrated the presence of the chitosan on the surface of the particles (<100 μm), dependent on the polymer composition of the microparticles. The interaction between the mucin solutions and the PLGA/chitosan microparticles increased significantly with an increasing concentration of mucin and chitosan. Conclusions: The strong interaction of mucin with the chitosan present on the surface of the particles suggests a potential use of the mucoadhesive carriers for gastroretentive and oral controlled drug release

Radical scavenging activity of 5-methylpyrrolidinone chitosan and dibutyryl chitin

This study compares the behaviour of 5-methylpyrrolidinone chitosan (MPC), a substituted hydrophilic polymer bearing free -OH and -NH2 groups, and dibutyryl chitin (DBC), a novel lipophilic O- and N-persubstituted chitin, toward free radicals. By means of EPR measurements their capacity of trapping radicals photochemically generated from PTOC esters was assessed. The fate of radicals inside the polysaccharides was checked on the basis of the structure of products obtained after photolysis and characterized by NMR spectroscopy. The experimental data clearly demonstrated that hydrophilic chitosans and persubstituted chitins possess remarkable radical blocking activity even though the nature of the process should be rather different between MPC and DBC. The DBC substrate hosts the radicals in protected and poorly reactive environment, whereas hydrophilic chitosan substrates favor a more rapid annealing of the radicals. MPC takes part in radical reactions with a consequent likely fragmentation of the polymer chain. A photochemical experiment carried out on chitosan confirmed the behaviour observed for MPC