Pectin/lignocellulose nanofibers/chitin nanofibers bionanocomposite as an efficient biosorbent of cholesterol and bile salts.

A new biosorbent Ca-crosslinked pectin/lignocellulose nanofibers/chitin nanofibers (PLCN) was synthesized for cholesterol and bile salts adsorption from simulated intestinal fluid during gastric-intestinal passage. The physico-chemical properties of PLCN were studied using SEM, FTIR, XRD, DSC and BET. Before gastrointestinal passage, PLCN had an amorphous single-phase, compact structure formed via hydrogen and van der Waals bonds that revealed an irregular shape with the shriveled surface but watery condition and enzymatic digestion led to create a porous structure without destruction because of the water-insoluble nanofibers, therefore increasing the adsorption capacity. The maximum adsorption capacity reached 37.9 and 5578.4 mg/g for cholesterol and bile salts, respectively. Freundlich isotherm model indicated the reversible heterogeneous adsorption of both cholesterol and bile salts on PLCN. Further, their adsorption followed pseudo-second order kinetic model. These results suggest that PLCN has potential as a gastrointestinal-resistant biosorbent for cholesterol and bile salts adsorption applicable in medicine and food industry.

Biodistribution and excretion of radioactivity after the administration of 166Ho-chitosan complex (DW-166HC) into the prostate of rat.

PURPOSE: The objective of this study was to determine the fate of the 166Ho-chitosan complex (DW-166HC) in rats by examining its absorption, distribution and excretion after administration into the prostate. METHODS: About 100 microCi of DW-166HC [containing 0.1875 mg of Ho(NO3)3.5H2O and 0.25 mg of chitosan] was administered intraprostatically. The level of radioactivity in blood, urinary and faecal excretion, and radioactivity distribution were examined. To determine the effect of chitosan in DW-166HC, 166Ho nitrate alone [0.1875 mg of Ho(NO3)3.5H2O] was administered into the prostate of male rats, and radioactivity distribution was examined using whole-body autoradiography. RESULTS: After administration of DW-166HC into the prostate, cumulative urinary and faecal excretion over the period 0-72 h was 0.35% and 0.11%, respectively. The radioactivity at the administration site was extremely high at all time points up to 144 h (>98% of injected dose). The small amount of radioactivity which did transfer from the administration site distributed mainly to the liver, spleen, kidney cortex and bone. Compared with the DW-166HC group, the group that received 166Ho nitrate alone displayed three- to fourfold higher levels of radioactivity in the main tissues, including liver, spleen, kidney cortex and bone, at 24 h after administration (P < 0.05). CONCLUSION: The results of this study show clearly that most of the administered DW-166HC remained at the administration site. It is concluded that the chitosan complex may be used to retain 166Ho within a limited area in cancer of the prostate.

Preparation of alginate/chitosan microcapsules and enteric coated granules of mistletoe lectin.

The aqueous extract of European mistletoe (Viscum album, L.) has been used in cancer therapy. The purified mistletoe lectins, main components of mistletoe, have demonstrated cytotoxic and immune-system-stimulating activities. Korean mistletoe (Viscum album L. coloratum), a subspecies of European mistletoe, has also been reported to possess anticancer and immunological activities. A galactose- and N-acetyl-D-galactosamine-specific lectin (Viscum album L. coloratum agglutinin, VCA) with Mr 60 kDa was isolated from Korean mistletoe. Mistletoe preparations have been given subcutaneously due to the low stability of lectin in the gastrointestinal (GI) tract. In the present study, we investigated the possibility of alginate/chitosan microcapsules as a tool for oral delivery of mistletoe lectin. In addition, our strategy has been to develop a system composed of stabilizing cores (granules), which contain mistletoe lectin, extract or powder, coated by a biodegradable polymer wall. Our results indicated that successful incorporation of VCA into alginate/chitosan microcapsules has been achieved and that the alginate/chitosan microcapsule protected the VCA from degradation at acidic pH values. And coating the VCA with polyacrylic polymers, Eudragit, produced outstanding results with ideal release profiles and only minimal losses of cytotoxicity after manufacturing step. The granules prepared with extract or whole plant produced the best results due to the stability in the extract or whole plant during manufacturing process.

Thiolated chitosans: development and in vitro evaluation of a mucoadhesive, permeation enhancing oral drug delivery system.

It was the aim of this study to develop a mucoadhesive, permeation enhancing delivery system for orally administered poorly absorbed drugs. Chitosan was modified by the immobilisation of thiol groups utilising 2-iminothiolane (Traut's reagent). The permeation enhancing effect of the resulting chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) in combination with the permeation mediator glutathione (GSH) was evaluated in Ussing chambers on freshly excised small intestinal mucosa from guinea pigs using rhodamine 123 as marker for passive drug uptake. The mucoadhesive properties of the chitosan-TBA conjugate adjusted to pH 3, 5 and 7 were evaluated via the rotating cylinder method and via tensile studies. Release studies were performed with tablets comprising 10% cefadroxil used as model drug, 10% GSH and 80% chitosan-TBA conjugate pH 3 in 100 mM phosphate buffer pH 6.8 at 37 degrees C. Results showed a 3-fold higher permeation enhancing effect of the chitosan-TBA conjugate/GSH system in comparison to unmodified chitosan. Mucoadhesion studies revealed that the lower the pH of the thiolated chitosan is, the higher are its mucoadhesive properties. Release studies showed a sustained release of both cefadroxil and GSH over several hours. This delivery system might represent a promising novel tool in order to improve the therapeutic efficacy of various drugs which are poorly absorbed from the gastrointestinal tract.

The formation and permeability of drugs across free pectin and chitosan films prepared by a spraying method.

This study has investigated the permeation of drugs through free films made of pectin and chitosan. The background for this study is the intended use of the films as coating material in a colon-specific drug delivery device. The factors that varied when making the films were the pectin source and grade of the pectin, degree of deacetylation of the chitosan and ratio between pectin and chitosan. The permeability of the model drug in 0.1 M HCl was low with an average drug release of 1.3 x 10(-3)%/cm. The films containing high content of chitosan showed exponential kinetics while the films containing high content of pectin showed 0-order kinetics. The release of drug in phosphate buffer pH 6.8 showed 0-order kinetics. The lowest permeability was obtained for a film consisting of a high content of pectin to chitosan, chitosan with a high degree of deacetylation and non-amidated low methoxylated citrus pectin. The permeation of paracetamol for this combination was 9.4 x 10(3)%/cm. This film combination had a combined diffusion of only 0.046%/cm after 1 h in 0.1 M HCl and 4 h in phosphate buffer pH 6.8.

Release of albumin from chitosan-coated pectin beads in vitro.

The release behavior of albumin from chitosan-coated pectin beads in vitro was investigated. The factors, such as concentration of CaCl(2), molecular weight of chitosan, pH of chitosan solution, and pH of release medium, which can have a significant effect on the release behavior from the beads, were discussed in this study. The loading efficiency (LE) of albumin showed maximum value when the concentration of CaCl(2) and the weight ratio of pectin to albumin were 2 wt.% and 2, respectively. The release of albumin from pectin beads could be retarded by coating with chitosan at various pH medium. The increase of the concentration of CaCl(2) induced the decrease of albumin release for uncoated-pectin beads, but not much difference of release for coated-pectin ones. The higher molecular weight of chitosan showed less albumin release than the lower one. The release of albumin from the chitosan-coated pectin beads was dependent on pH of coating solution and release medium, which might affect the degree of swelling of pectin beads.

5-Fluorouracil in topical liposome gels for anticancer treatment--formulation and evaluation.

Liposome gels bearing an antineoplastic agent, 5-fluorouracil, intended for topical application have been prepared and drug release properties in vitro have been evaluated. Different formulations of liposomes were prepared by the film hydration method by varying the lipid phase composition (PL 90H/cholesterol mass ratio) and hydration conditions of dry lipid film (drug/aqueous phase mass ratio). Topical liposome gels were prepared by incorporation of lyophilized liposomes into a structured vehicle (1%, m/m, chitosan gel base). Also, hydrogels containing different concentrations of 5-fluorouracil were prepared and drug release properties were investigated. The rate of drug release from liposome gels was found to be dependent on the bilayer composition and the dry lipid film hydration conditions. Also, liposomes embedded into a structured vehicle of chitosan showed significantly slower release than hydrogels. The drug release obeyed the Higuchi diffusion model, while liposomes acted as reservoir systems for continuous delivery of the encapsulated drug.

Development and in vitro evaluation of novel floating chitosan microcapsules for oral use: comparison with non-floating chitosan microspheres.

Floating (F) microcapsules containing melatonin (MT) were prepared by the ionic interaction of chitosan and a negatively charged surfactant, sodium dioctyl sulfosuccinate (DOS). The DOS/chitosan complex formation was confirmed employing infrared spectroscopy, differential scanning calorimetry (DSC), solubility and X-ray diffraction analysis. The characteristics of the F microcapsules generated compared with the conventional non-floating (NF) microspheres manufactured from chitosan and sodium tripolyphosphate (TPP) were also investigated. The effect of various factors (crosslinking time, DOS and chitosan concentrations, as well as drug/polymer ratio) on microcapsule properties were evaluated. The use of DOS solution in coagulation of chitosan produced well-formed microcapsules with round hollow core and 31.2-59.74% incorporation efficiencies. Chitosan concentration and drug/polymer ratio had a remarkable effect on drug entrapment in DOS/chitosan microcapsules. The dissolution profiles of most of microcapsules showed near zero order kinetics in simulated gastric fluid (S.G.F: pH 1.2). Moreover, release of the drug from these microcapsules was greatly retarded with release lasting for several hours (t(50%) (S.G.F.): 1.75-6.7 h, depending on processing factors), compared with NF microspheres where drug release was almost instant. Most of the hollow microcapsules developed tended to float over simulated biofluids for more than 12 h. Swelling studies conducted on various drug-free formulations, clearly indicated that DOS/chitosan microcapsules showed less swelling and no dissolution in S.G.F. for more than 3 days, whereas, TPP/chitosan microspheres were markedly swollen and lost their integrity in S.G.F. within 5 h. Therefore, data obtained suggest that the F hollow microcapsules produced would be an interesting gastroretentive controlled-release delivery system for drugs.

In vitro evaluation of microcrystalline chitosan (MCCh) as gel-forming excipient in matrix granules.

Although much research has been carried out into the effects of chitosan and its chemical properties on drug release, less attention has been paid to the effects of its physical properties. The aim of this study was to characterize microcrystalline chitosan (MCCh) as a gel-forming excipient. Matrix granules containing chitosans of differing physicochemical properties (crystallinity, molecular weight, degree of deacetylation) and ibuprofen or paracetamol as model drugs were prepared. Gel formation by the chitosans in the granules and subsequent effects on drug release were studied at pH 1.2 and pH 5.8. The chitosan granules acted as slow-release formulations in the case of ibuprofen (a class-II drug in the Biopharmaceutics Classification System) but with paracetamol (class-I) no controlled-release formulation could be developed. Microcrystalline grades of chitosan had the most marked retardant effects on drug release, with the efficacy of gel formation by MCCh explaining the results. The kinetic constant for ibuprofen release (at pH 5.8) ranged from 22%.h(-1) (MCCh) to 31%.h(-1) (unmodified chitosan). The release rate was easily controlled by varying the amount or molecular weight of MCCh, and to a lesser extent by the degree of deacetylation. The effects were most pronounced when pH was markedly acidic, suggesting that MCCh granules might be particularly useful in preparing stomach-specific slow-release dosage forms.

Formulation and in vivo evaluation of chlorhexidine buccal tablets prepared using drug-loaded chitosan microspheres.

This investigation deals with the development of buccal formulations (tablets) based on chitosan microspheres containing chlorhexidine diacetate. The microparticles were prepared by a spray-drying technique, their morphological characteristics were studied by scanning electron microscopy and the in vitro release behaviour was investigated in pH 7.0 USP buffer. Chlorhexidine in the chitosan microspheres dissolves more quickly in vitro than does chlorhexidine powder. The anti-microbial activity of the microparticles was investigated as minimum inhibitory concentration, minimum bacterial concentration and killing time. The loading of chlorhexidine into chitosan is able to maintain or improve the anti-microbial activity of the drug. The improvement is particularly high against Candida albicans. This is important for a formulation whose potential use is against buccal infections. Drug-empty microparticles have an anti-microbial activity due to the polymer itself. Buccal tablets were prepared by direct compression of the microparticles with mannitol alone or with sodium alginate. After their in vivo administration the determination of chlorhexidine in saliva showed the capacity of these formulations to give a prolonged release of the drug in the buccal cavity.

Stomach-specific anti-H. pylori therapy. I: Preparation and characterization of tetracyline-loaded chitosan microspheres.

The main objective of the study was to develop a stomach-specific drug delivery system to increase the efficacy of tetracycline against Helicobacter pylori. Chitosan microspheres were prepared by ionic cross-linking and precipitation with sodium sulfate. Two different methods were used for drug loading. In method I, tetracycline was mixed with chitosan solution before the simultaneous cross-linking and precipitation. In method II, the drug was incubated with pre-formed microspheres for 48 h. The cumulative amount of tetracycline that was released from chitosan microspheres and the stability of the drug was examined in different pH medium at 37 degrees C. Microspheres with a spherical shape and an average diameter of 2.0-3.0 microm were formed. When the drug was added to the polymer solution before cross-linking and precipitation only 8% (w/w) was optimally incorporated in the final microsphere formulation. When the drug was incubated with the pre-formed microspheres, on the other hand, a maximum of 69% (w/w) could be loaded. Thirty percent of tetracycline either in solution or when released from microspheres was found to degrade at pH 1.2 in 12 h. The preliminary results from this study suggest that chitosan microspheres can be used to incorporate antibiotic drugs and may be effective when administered locally in the stomach against H. pylori.

[Internal pharmacokinetical study on genistein chitosan microsphere capsule].

OBJECTIVE: To compare the distribution of genistein chitosan microsphere capsule (M.C) in vivo in rats with that of genistein common capsule (C.C). To research slow-released target microsphere capsule. METHOD: The study on pharmacokinetics of M.C and C.C were analyzed by HPLC and 3P97 software. RESULTS: The concentration of M.C distributed among various organs decreased slower than those of C.C and were able to keep a certain concentration for a long time. Genistein common capsule mainly distributed in livers of rats, while genistein chitosan microsphere capsule distributed mainly in lungs and spleens of rats. CONCLUSION: The chitosan microsphere capsule of genistein has better slow-release and has tendency to distribute in lungs and spleens.