Overall, this novel class of thiolated chitosans containing protected thiol groups, offer the advantage of not being subject to any oxidation at all, which opens the door for numerous additional applications. The reduced thiol functions on the chitosan backbone enable thiolated chitosans not only to form disulfide bonds with mucus glycoproteins, but also to form inter as well as intramolecular disulfide bonds. Optimization and development of insulin nanoparticles by. After continuous stirring at room temperature for 4 h, the mixture was dialyzed against deionized water for 5 days and lyophilized at 50 c and 20 pa in order to immobilize the peptide within the chitosan chitosan. Development of mucoadhesive thiolated chitosan nanoparticles for. Sep 15, 2011 chitosan and thiolated chitosan, by f. As free thiol moieties are essential for all the features mentioned above, it was the aim of. Correlation of the structure, properties, and antimicrobial activity of a soluble thiolated chitosan derivative bing han,1 yan wei,2 xiaolong jia,3 juan xu,3 gang li3 1department of orthodontics, peking university school and hospital of stomatology, beijing 81, peoples. In this research, three types of nanoparticle formulation from commercial pcl and selfsynthesized d. Li deparment of chemistry, sichuan college of education, chendu 610041, sichuan province, china.
The present study aimed to formulate thiolated chitosan nanoparticles of zolmitriptan for brain targeting via intranasal drug delivery. Thiolated chitosan nanoparticles enhance antiinflammatory. Stable and mucoadhesive, lyophilised, thiolated chitosan xerogels, loaded with insulin for buccal mucosa deliv ery, in place of the currently used parenteral route have been developed. Preparations, properties and applications of chitosan based.
Effect of thiolfunctionalisation on chitosan antibacterial. Nano express open access thiolated chitosanmodified. Enzymatic degradation of thiolated chitosan request pdf. Zeroorder controlled release of bmp2derived peptide p24. Low molecular weight chitosan was modified to thiolated chitosan in the laboratory and confirmed with ftir and dsc studies. A novel approach has been developed to synthesize thiolated sub100 nm organosilica nanoparticles from 3mercaptopropyltrimethoxysilane mpts through its selfcondensation in dimethylsulfoxide in contact with atmospheric oxygen.
Buccal mucosa, chitosan, enzyme inhibitor, insulin, permeation enhancement, xerogel. Obtained from the arthropod family members like lobster. The uptake of the cationic marker compound rhodamine 123 was 3fold higher in the presence of thiolated chitosan. Possible formation of thiourea and disulfide crosslinks. To improve water solubility and bioavailability, curcumin cur was encapsulated by liposomes curlip, which was further coated with thiolated chitosan cssh to form liposomal hydrogels csshcurlip gel. Mg of tcs which exhibited successful thiolation of the chitosan. To date, three different thiolated chitosan derivatives have been. Sustained release thiolated chitosan based nanoparticulate. Synthesis and characterization of thiolated hexanoyl glycol chitosan. Correlation of the structure, properties, and antimicrobial activity of a soluble thiolated chitosan derivative bing han,1 yan wei,2 xiaolong jia,3 juan xu,3 gang li3 1department of orthodontics, peking university school and hospital of stomatology, beijing 81, peoples republic of china 2department of geriatric dentistry, peking university school and hospital of stomatology, beijing 81. First of all have to synthesize methylated pyridinyl chitosan and then for tmpc lcysteine should be attached to methylated pyridinyl chitosan by the. Thiolated chitosan was synthesized by introducing thioglycolic acid tga to chitosan via amide bond formation mediated by a carbodiimide. Thiolated chitosan has several advantageous features compared to native chitosan such as enhancement of solubility at low degree of substitution and mucoadhesive and cellular permeation properties.
The aim of this study was to synthesize a novel thiolated chitosan with higher reactivity in order to further improve mucoadhesion. Research article synthesis and characterization of new. Oral chemotherapy is a key step towards chemotherapy at home, a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. Due to the immobilization of thiol groups on the chitosan. Thiolated chitosan nanoparticles for enhancing oral. Saremi s, atyabi f, akhlaghi sp, ostad sn, dinarvand r. Hec is inert cellulose and its properties such as biocompatibility, physiochem. Thiolated chitosan masked polymeric microspheres with.
Thiolated chitosan was synthesized by modifying the previously reported method. The formation of mpts nanoparticles proceeds through the condensation of methoxysilane groups and simultaneous disulfide bridging caused by partial oxidation. The hydrogels were thermosensitive with in situ injectable performance, which were fluidic at room temperature and gelled quickly at 37 c. The solubility test showed that the thiolated cs derivative was. The current insulin therapy is via subcutaneous injection, which often fails to mimic the glucose homeostasis that occurs in normal individuals. Stability of thiol moieties under different storage conditions 333 plasma calcium level after orally administered calcitonin being incorporated in thiolated chitosan15. Sustained release thiolated chitosan based nanoparticulate in. Thiolated chitosan nanoparticles as a delivery system for antisense therapy. The degree of thiolation was determined by reacting the thiol groups with ellmans reagent 5,5dithiobis2nitrobenzoic acid and reading the absorbance at 412 nm spectrophotometrically. Fabrication of gnrs by seedmediated growth method with the aid of cetyltrimethylammonium bromide ctab is a popular approach.
The modifications discussed here include amphiphilic chitosan derivatives, naminoalkyl chitosan, carboxymethyl chitosan, thiolated chitosans, phosphorylated chitosan, etc. Due to the formation of disulfide bonds with mucus glycoproteins. Thiolated chitosans also display, beside their strong mucoadhesive and permeation enhancing properties, excellent cohesive properties. Dec 18, 2010 gold nanorod gnr has great potential in the field of cancer therapy because of its photophysical property in converting nearinfrared nir laser light into heat. In order to understand the mechanism of the grafting of thiolated chitosan onto wool, glutathione was used as a model compound for wool in the research.
A glucomannan and chitosan fiber supplement decreases plasma cholesterol and increases cholesterol excretion in overweight normocholesterolemic humans. Multifunctional chitosan nanoparticles for tumor imaging and therapy, by j. It was hypothesized that adsorption of theophylline to chitosan. The increase was 7, 3 2, and 168 fold m t hiol groups per gra m of polymer, respectively. Synthesis and characterization of new thiolated chitosan. Buy chitosan for biomaterials i advances in polymer science. Preparation and evaluation of nanoparticles composed of. However, insulin cannot be well absorbed orally because of its rapid enzymatic degradation in the.
The synthesized peptide 5% or 10% of the weight of chitosan in 15 ml dmso was added into the thiolated chitosan solution. Asnonionicpolysaccharide,hydroxyethylcellulosehecisone of the obvious choices for pharmaceutical application. As a result, anticancer drugs show an improved bioavailability and residence time. Special emphasis has been given to the development of chitosan based polyelectrolyte complexes, graft copolymerized chitosan and chitosan based stimuliresponsive. Oral delivery is the most convenient administration route. Many biochemists have found that chitosan as biocompatible, biodegradable and non toxic which made wide applicability.
Synthesis and characterization of phsensitive thiol. Regarding the drug ee, it can be seen from table 1 that the 5% thiolated chitosan modified plapcltpgs nanoparticles achieved much higher ee than the 5% thiolated chitosan modified pcl nanoparticles. Docetaxel was obtained from cipla mumbai, india, taxotere, an injectable commercially available formulation of dtx, was from sano aventis france, and chitosan chitoclear with molecular weight of. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a pdf plugin installed and enabled in your browser. Jul 18, 2012 in the second step, 500 mg of chitosan was hydrated in 4 ml of 1 m hcl and dissolved by the addition of demineralized water to obtain a 2. Thiomers are thiolated polymers with excellent mucoadhesive properties. The structures of thiolated chitosan reacted with glutathione and wool fabrics grafted with thiolated chitosan were investigated by ftir, cnmr, xps, xrd, sem.
Thiol containing chitosan tcs, found to be soluble in water, was synthesized by. Synthesis of thiolated and sprotected thiolated conjugates. The thiolated chitosan was synthesized by reaction of thiogycolic acid and chitosan in presence of catalyst. Chitosan supplementation does not affect fat absorption in healthy males fed a highfat diet, a pilot study. Chitosan, a versatile natural polysaccharide, the second most abundant natural polymer. Correlation of the structure, properties, and antimicrobial. So far, the alkyl thiomers chitosan cysteine, chitosan thiobutylamidine, chitosan thioglycolic acid, chitosan nacetylcysteine, and chitosan thioethylamidine and the aryl thiomers chitosan 6mercaptonicotinic acid and chitosan 4mercaptobenzoic acid have been generated. Mg and the number of disulfide bonds was calculated to be 96. Thiolated polymers or designated thiomers are experimental polymers used in biotechnology product development with the intent to enhance absorption of drugs. Thiolated chitosan nanoparticles as a delivery system for.
Nov 20, 20 removal of cuii and cdii from wastewater using porous chitosan beads is likely to be enhanced by the introduction of thiol groups. Cd with thiol groups and to assess its solubilityimproving and permeationenhancing properties for a bcs class iv drug in vitro as well as in vivo. The thiolated chitosan display in situ gelling features due to the phdependent alkaline ph formation of intermolecular disulphide bonds which makes the application of thiolated chitosan on intestinal mucosa and can guarantee prolonged controlled release of embedded therapeutic ingredients. The mucoadhesive properties of chitosan can be increased by attaching a thiol sh containing side groups to its backbone chains through ionic. Thiolated chitosans constitute an integral part of designated thiomers, which are thiolated polymers widely investigated for noninvasive drug delivery. Research article open access synthesis and characterization of thiolated hexanoyl glycol chitosan as a mucoadhesive thermogelling polymer ik sung cho1, hye min oh1, myeong ok cho1,2, bo seul jang1, jungkyo cho3, kyoung hwan park1,2, sunwoong kang2,4 and kang moo huh1 abstract. Nair1, and rangasamy jayakumar1 1 amrita center for nanosciences and molecular medicine, amrita institute of medical sciences. Discriminated effects of thiolated chitosancoated pmma. This might be contributed to the selfemulsification effect of tpgs segment in the plapcltpgs copolymer 2, 8. Supporting information combinatorial photothermal and. The subphase solutions in the langmuir monolayer measurements were prepared by dissolving 1 mgml freeze dried chitosan and thiolated chitosan conjugates in a 0. Extraction of chitin from chitosan from exoskeleton of shrimp. However, due to high cytotoxicity of ctab, it is necessary to modify the surface of ctabpassivated. Discriminated effects of thiolated chitosan coated pmma paclitaxelloaded nanoparticles on different normal and cancer cell lines seyedeh parinaz akhlaghi, pharmda, shahrooz saremi, pharmda, seyed nasser ostad, phda, rassoul dinarvand, phda,b, fatemeh atyabi, phda,b.
Dtxloaded nanoparticles were prepared by emulsion polymerization method using cerium ammonium nitrate as an initiator. Chitosanbased particulate systems for noninvasive vaccine delivery, by s. Enhanced oral delivery of docetaxel using thiolated. Development and in vivo evaluation of an oral delivery system for leuprolide. In case of thiolated chitosan, for instance, a more than 10,000fold increase in viscosity within a few minutes was shown. Synthesis of thiolated chitosan and preparation nanoparticles with sodium alginate for ocular drug delivery xuan zhu, 1 meiqin su, shaoheng tang, 2 lingsong wang, xinfang liang, 1 feihong meng, ying hong, 1 zhiran xu 1 1school of pharmaceutical science, xiamen university, xiamen, china. This is a pdf file of an unedited manu script that has been accepted. Pdf controlled release matrix tablet formulation using. Preweighed thiolated chitosan was dissolved in deionized water at a concentration of 0.
Synthesis of thiolated chitosan and preparation nanoparticles. Thiolated mucoadhesive and pegylated nonmucoadhesive. So in order to increase the mucoadhesive properties of pla or plga microspheres, their surface could be coated with chitosan. In the second step, 500 mg of chitosan was hydrated in 4 ml of 1 m hcl and dissolved by the addition of demineralized water to obtain a 2. Enhanced oral delivery of docetaxel using thiolated chitosan. Lyophilized thiolated chitosan chitosan thioglycolic acid conjugates, fig. Synthesis and characterization of biodegradable thiolated. This is because, in accordance with the hard soft acid base concept, the soft lewis base of sh forms a strong bond with soft lewis acid of cdii or with borderline lewis acids such as cuii. Thereafter, the reactive nhsester was added dropwise into the chitosan hydrochloride solution, with the ph maintained at 5 using 10 m naoh. Preparation and in vitro evaluation of thiolated chitosan. Insulin therapy has been the best choice for the clinical management of diabetes mellitus. The hgc was further modified to include thiol groups to improve the mucoadhesive property of thermogelling hgc. So far, the alkyl thiomers chitosancysteine, chitosanthiobutylamidine, chitosanthioglycolic acid, chitosannacetylcysteine, and chitosanthioethylamidine and the aryl thiomers chitosan6mercaptonicotinic acid and chitosan4mercaptobenzoic acid have been generated. Development of mucoadhesive thiolated chitosan nanoparticles for biomedical applications a.
Above ph 6, cs loses its positivecharge density, and induces the formation of aggregates and precipitates. Design and synthesis of a novel cationic thiolated polymer. Synthesis of thiolated chitosan nanoparticles was as follows. Thiolated chitosanmodified plapcltpgs nanoparticles for. The aim of this study was to evaluate a nanoparticulate system with mucoadhesion properties composed of a core of polymethyl methacrylate surrounded by a shell of thiolated chitosan chgshpmma for enhancing oral bioavailability of docetaxel dtx, an anticancer drug. Chitosan thiolated nanoparticles were synthesized by adaptation of zhu et al. Controlled release matrix tablet formulation using. The lyophilized thiolated chitosan appeared as a white fibrous powder with improved aqueous solubility. The main objective of this work was to develop nanoparticles nps of a mucoadhesive polymer based on chitosan for biomedical applications. Tcs provides much better mucoadhesive properties than cs, which can be explained by the formation of covalent disulfide bonds between the thiol groups and the mucus glycoproteins, which are much stronger than non. Znonps embedded biodegradable thiolated bandage for. Preparation and evaluation of nanoparticles composed of thiolated methylated pyridinyl chitosan as a new strategy for bucaldrug delivery of insulin babak zolfagharnia1, elaheh mortazavian 2, davood kaviani3, morteza rafieetehrani 1department of pharmaceutics, faculty of pharmacy, tehran university of medical sciences, tehran, iran. The chemical structure of the cs derivative was confirmed by fourier transform infrared spectroscopy and 1 h.
The nanoparticles were suspended in thiolated chitosan solution at a concentration of 9. Functional characterisation and permeation studies of. Sprotected thiolated chitosan represents a stable and promising tool for the development of various mucoadhesive drug delivery systems. Characterization of thiolated chitosan nanoparticles. Pdf the polymer properties of chitosan are spectacularly modified with their conversion to sulfhydrylbearing derivatives. Thiomer compounds with low molecular mass are covalently bound to a polymeric backbone consisting of biodegradable polymers, such as chitosan, hyaluronic acid, gelatin, polyacrylates, cyclodextrins, or.
Chitosan is an amino polysaccharide prepared by processing shrimp waste shell which involves partial deacetylation of chitin. To solve this problem, thiolated chitosan tcs, comprising a new generation of mucoadhesive polymers thiolated polymers or thiolmers has been produced. Chitosan, a polymer derived from chitin, has been used for nasal drug delivery because of its biocompatibility, biodegradability and bioadhesiveness. The purpose of the study was to develop a per6thiolated. The polymer properties of chitosan are spectacularly modified with their conversion to sulfhydrylbearing derivatives. Research article enhanced oral delivery of docetaxel using. A further modification is based on the immobilization of thiol bearing moieties on the polymeric backbone of chitosan. Synthesis and characterization of thiolated hexanoyl. The purpose of this study is about the preparation and evaluation of nanoparticles composed of thiolated methylated pyridinyl chitosan tmpc which are made p. The goal of the present study was to synthesize mucoadhesive polymer thiolated chitosan. Optimization of thiolated chitosan nanoparticles for the. The measurements were performed with a langmuir trough nima, model 1232d1d2 mounted on an antivibration table and housed in an isolated box. Chitosan and its derivatives as promising drug delivery.
The purpose of the study was to formulate and evaluate thiolated chitosan based nanoparticulate mucoadhesive ophthalmic in situ gelling system of prulifloxacin for bacterial keratoconjunctivitis. Various properties of chitosan are improved by the immobilization of thiol groups. Gold nanorod gnr has great potential in the field of cancer therapy because of its photophysical property in converting nearinfrared nir laser light into heat. Synthesis and characterization of thiolated chitosan beads. The ph of the thiolated chitosan, providing the highest mucoadhesive properties, was identi ed to be ph 3 for chtba bernkopschnurch et a l. The synthesis of sprotected thiolated chitosan is a towstep procedure. Tmc, carboxyalkyl chitosan, thiolated chitosan, sugarbearing chitosan, bile acidmodified chitosan and cyclodextrinlinked chitosan 1520. Cd were replaced by iodine, followed by substitution with. Based on this conjugate, nanoparticles with pdna were.
The zeta potential of nanoparticles was determined to be 7. Chitosan the biodegradable polymer chitosan is prepared from removing acetyl group in alkaline condition from chitin, which is widely found polysaccharide in nature. Sustained release thiolated chitosan based nanoparticulate in situ gel for ocular delivery of prulifloxacin volume. The chemical modification in certain chitosan chains allows the formation of internal and external bisulfide bonds. Thiolated chitosan nanoparticles for enhancing oral absorption of docetaxel. In the thiolbearing derivatives, the mucoadhesive, cohesive properties and in situ gelling features are strongly improved. The xerogels were backed with impervious ethyl cellulose. These high in situ gelling properties can also be used for numerous further reasons such as for parenteral formulations, as coating material or for food additives. Pdf development of mucoadhesive thiolated chitosan. The nh 2 group of chitosan helps in preparation of various chitosan conjugates with acids. Injectable and in situformable thiolated chitosancoated. Carapace waste of shrimp, crab and lobster are the sources of chitin.
A thiolated chitosan cs derivative was synthesized by the introduction of thioglycolic acid to cs via amide. Because of its availability via an efficient synthetic pathway and its mucoadhesive properties based on the capability to bind cysteine subunits, chitosan tga seems to be a promising. For this purpose, 4mercaptobenzoic acid was chosen to be covalently attached to chitosan. Supporting information combinatorial photothermal and immuno. The thiolated chitosan was characterized using ftir and. Controlled release matrix tablet formulation using synthesized nacyl thiolated chitosan derivatives article pdf available. According to thermodynamics of the first phase, the structural arrangement of thiolated chitosan chains occurs as a spontaneous process. Yhee, heebeom koo, dong eun lee, kuiwon choi, ick chan kwon and kwangmeyung kim. It is made by treating the chitin shells of shrimp and other crustaceans with an alkaline substance, like sodium hydroxide. The number of thiol groups immobilized on chitosan was calculated to be 161. Theophylline is a drug that reduces the inflammatory effects of allergic asthma but is difficult to administer at an appropriate dosage without causing adverse side effects.
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