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1.
The main objective of this study was to develop a local, oral mucoadhesive metronidazole benzoate (MET) delivery system that can be applied and removed by the patient for the treatment of periodontal diseases. The results of present study revealed that the retention time of MET at its absorption site could be increased by formulating it into nanoparticles using thiolated chitosan (TCS)-poly(methacrylic acid) (PMAA). The nanoparticles of MET prepared from TCS-PMAA may represent a useful approach for targeting its release at its site of absorption, sustaining its release and improving its oral availability.  相似文献   

2.
The film-forming ability of chitosan and binary mixtures of chitosan and native amylose corn starch (Hylon VII) was evaluated with free films prepared by a casting/solvent evaporation method. Unplasticized and plasticized free chitosan films in aqueous acetic acid and respective films containing a mixture of chitosan and native amylose starch in acetic acid were prepared. Glycerol, sorbitol, and i-erythritol were used as plasticizers. Solid-state and mechanical properties of the films were studied by powder x-ray diffractometry (XPRD), differential scanning calorimetry (DSC), and a materials testing machine. The films composed of a mixture of chitosan and native amylose starch in acetic acid were clear and colorless. A plasticizer concentration of 20% wt/wt (of the polymer weight) ws sufficient to obtain flexible films with all samples tested. X-ray diffraction patterns and DSC thermograms indicated an amorphous state of the films independent of the type of plasticizer used. In conclusion, incorporation of native amylose com starch into chitosan films improves the consistency and the mechanical properties of the films.  相似文献   

3.
The present work is focused on the development of thiolated film for fluconazole buccal delivery. To this end, unmodified polymers chitosan and sodium carboxymethylcellulose (NaCMC) backbone was covalently modified by thioglycolic acid (TGA) and cysteine, respectively. The thiolated buccoadhesive film was evaluated in terms of thickness, weight uniformity, water-uptake capacity, drug content, and release patterns. Moreover, mucoadhesion profile was investigated on buccal mucosa. The resulting chitosan–TGA and NaCMC–cysteine conjugates displayed 171?±?13 and 380?±?19 μmol thiol groups per gram of polymer (mean?±?SD; n?=?3), respectively. The water binding capacity of the thiolated film was significantly ~2-fold higher (p?<?0.05) as compared to unmodified film. The obtained thiolated film displayed 5.8-fold higher mucoadhesive properties compared with corresponding film. Controlled release of drugs from film was observed over 8 h. The transport of fluconazole across excised buccal mucosa was enhanced up to 17-fold in comparison with fluconazole applied in buffer. Based on these findings, thiolated film seems to be promising for fluconazole buccal delivery.  相似文献   

4.
Ryu JH  Lee Y  Kong WH  Kim TG  Park TG  Lee H 《Biomacromolecules》2011,12(7):2653-2659
Bioinspired from adhesion behaviors of mussels, injectable and thermosensitive chitosan/Pluronic composite hydrogels were synthesized for tissue adhesives and hemostatic materials. Chitosan conjugated with multiple catechol groups in the backbone was cross-linked with terminally thiolated Pluronic F-127 triblock copolymer to produce temperature-sensitive and adhesive sol-gel transition hydrogels. A blend mixture of the catechol-conjugated chitosan and the thiolated Pluronic F-127 was a viscous solution state at room temperature but became a cross-linked gel state with instantaneous solidification at the body temperature and physiological pH. The adhesive chitosan/Pluronic injectable hydrogels with remnant catechol groups showed strong adhesiveness to soft tissues and mucous layers and also demonstrated superior hemostatic properties. These chitosan/Pluronic hydrogels are expected to be usefully exploited for injectable drug delivery depots, tissue engineering hydrogels, tissue adhesives, and antibleeding materials.  相似文献   

5.
Chitosan, a polysaccharide, having structural characteristics similar to glycosaminoglycans, seems to be nontoxic and bioabsorbable. This study highlights the use of chitosan matrix for controlled drug delivery systems. The steroid drugs, namely testosterone, progesterone and beta-oestradiol were mixed with chitosan and the films were prepared by evaporation technique. The in vitro release profile of these steroids from the film matrix was monitored, as a function of time, in phosphate buffered saline (PBS, pH 7.4) at 37 degree C using a U-V-spectrophotometer. The degradation, of these chitosan and drug loaded chitosan films, was also investigated by weight loss and tensile strength studies. The steroid release from chitosan films was compared with the release of these drugs from their microbeads. It appears, the films and the microbeads stayed intact during the dissolution study of 90 days and the possibility of using these systems in contraceptive applications and novel drug delivery systems are discussed.  相似文献   

6.
The aim of this study was to evaluate the impact of various vehicles on mucoadhesive properties of thiolated chitosan nanoparticles both in vitro and in vivo. Nanoparticles (NPs) were prepared by in situ gelation technique followed by labeling with fluorescein diacetate. Comparative studies on mucoadhesion were done with these thiolated chitosan NPs and unmodified chitosan NPs (control). The obtained nanoparticles displayed a mean diameter of 164.2 ± 6.9 nm and a zeta potential of 21.5 ± 5 mV. In an in vitro adhesion study, unhydrated thiolated NPs adhered strongly to freshly excised porcine small intestine, which was more than threefold increase compared to the control. In contrast, in the presence of various vehicles (PEG 300, miglyol 840, PEG 6000, cremophor EL, and caprylic triglyceride), the mucoadhesive properties of thiolated NPs were comparatively weak. Thiolated NPs suspended in caprylic triglyceride, for example, had a percent mucoadhesion of 22.50 ± 5.35% on the mucosa. Furthermore, results from in vivo mucoadhesion studies revealed that the dry form of nanoparticles exhibits the strongest mucoadhesion, followed by nanoparticles suspended in PEG 300, miglyol, and 100 mM phosphate buffer, in that order. Three hours after administration, the gastrointestinal residence time of the dry form of thiolated NPs was up to 3.6-fold prolonged. These findings should contribute to the design of highly effective oral mucoadhesive nanoparticulate drug delivery systems.  相似文献   

7.
Two mucoadhesive thiolated polymers were synthesized by the covalent attachment of homocysteine thiolactone (HT) to chitosan and N,N,N-trimethyl-chitosan (TM-chitosan) at various chitosan:HT ratios. The amount of thiol and disulphide groups immobilized on the chitosan influenced the polymer's mucoadhesion positively and negatively, respectively, with the optimal chitosan:HT (w/w) ratio being found to be 1:0.1. The interaction between mucin and chitosan and its three derivatives was highest for the thiolated chitosan derivatives but was pH dependent. HT-chitosan and TM-HT-chitosan, with the thiol groups of 64.15 and 32.48 μmol/g, respectively, displayed a 3.67- and 6.33-fold stronger mucoadhesive property compared to that of the unmodified chitosan at pH 1.2, but these differences were only ∼1.7-fold at pH 6.4. The swelling properties of TM-HT-chitosan and HT-chitosan were higher than that of chitosan and TM-chitosan, attaining a swelling ratio of up to 240% and 140%, respectively, at pH 1.2 within 2 h.  相似文献   

8.
Chitosan has wide range of applications as a biomaterial, but barriers still exist to its broader use due to its physical and chemical limitations. The present study evaluated the properties of the polymeric blend films obtained from chitosan and potato starch by the casting/solvent evaporation method. The swelling properties of the different films studied as a function of pH showed that the sorption ability of the blend films increased with the increasing content of starch. Fourier transform infrared (FTIR) analyses confirmed that interactions were present between the hydroxyl groups of starch and the amino groups of chitosan in the blend films while the x-ray diffraction (XRD) studies revealed the films to exhibit an amorphous character. Thermogravimetric analyses showed that in the blend films, the thermal stability increased with the increasing starch content and the stability of starch and chitosan powders reduced when they were converted to film. The differential scanning calorimetry (DSC) studies revealed an endotherm corresponding to water evaporation around 100 degrees C in all the films and an exotherm, corresponding to the decomposition in the chitosan and blend films. Scanning electron microscopy (SEM) observations indicated that the blend films were less homogenous and atomic force microscopy (AFM) studies revealed the chitosan films to be smooth and homogenous, while the starch films revealed characteristic granular pattern. The blend films exhibited an intermediate character with a slight microphase separation. The starch-chitosan blend films exhibited a higher flexibility and incorporation of potato starch into chitosan films improved the percentage elongation.  相似文献   

9.
Nanoparticles composed of naturally occurring biodegradable polymers have emerged as potential carriers of various therapeutic agents for controlled drug delivery through the oral route. Chitosan, a cationic polysaccharide, is one of such biodegradable polymers, which has been extensively exploited for the preparation of nanoparticles for oral controlled delivery of several therapeutic agents. In recent years, the area of focus has shifted from chitosan to chitosan derivatized polymers for the preparation of oral nanoparticles due to its vastly improved properties, such as better drug retention capability, improved permeation, enhanced mucoadhesion and sustained release of therapeutic agents. Chitosan derivatized polymers are primarily the quaternized chitosan derivatives, chitosan cyclodextrin complexes, thiolated chitosan, pegylated chitosan and chitosan combined with other peptides. The current review focuses on the recent advancements in the field of oral controlled release via chitosan nanoparticles and discusses about its in vitro and in vivo implications.  相似文献   

10.
The control over the crystallinity of chitosan and chitosan/ovalbumin films can be achieved via an appropriate balance of the hydrophilic/hydrophobic interactions during the film formation process, which then controls the release kinetics of ovalbumin. Chitosan films were prepared by solvent casting. The presence of the anhydrous allomorph can be viewed as a probe of the hydrophobic conditions at the neutralization step. The semicrystalline structure, the swelling behavior of the films, the protein/chitosan interactions, and the release behavior of the films were impacted by the DA and the film processing parameters. At low DAs, the chitosan films neutralized in the solid state corresponded to the most hydrophobic environment, inducing the crystallization of the anhydrous allomorph with and without protein. The most hydrophilic conditions, leading to the hydrated allomorph, corresponded to non-neutralized films for the highest DAs. For the non-neutralized chitosan acetate (amorphous) films, the swelling increased when the DA decreased, whereas for the neutralized chitosan films, the swelling decreased. The in vitro release of ovalbumin (model protein) from chitosan films was controlled by their swelling behavior. For fast swelling films (DA?=?45%), a burst effect was observed. On the contrary, a lag time was evidenced for DA?=?2.5% with a limited release of the protein. Furthermore, by blending chitosans (DA?=?2.5% and 45%), the release behavior was improved by reducing the burst effect and the lag time. The secondary structure of ovalbumin was partially maintained in the solid state, and the ovalbumin was released under its native form.  相似文献   

11.
Recent concern that the increased use of triclosan (TCS) in consumer products may contribute to the emergence of antibiotic resistance has led us to examine the effects of TCS dosing on domestic-drain biofilm microcosms. TCS-containing domestic detergent (TCSD) markedly lowered biofouling at 50% (wt/vol) but was poorly effective at use levels. Long-term microcosms were established and stabilized for 6 months before one was subjected to successive 3-month exposures to TCSD at sublethal concentrations (0.2 and 0.4% [wt/vol]). Culturable bacteria were identified by 16S rDNA sequence analysis, and their susceptibilities to four biocides and six antibiotics were determined. Microcosms harbored ca. 10 log(10) CFU/g of biofilm, representing at least 27 species, mainly gamma proteobacteria, and maintained dynamic stability. Viable cell counts were largely unaffected by TCSD exposure, but species diversity was decreased, as corroborated by denaturing gradient gel electrophoresis analysis. TCS susceptibilities ranged widely within bacterial groups, and TCS-tolerant strains (including aeromonads, pseudomonads, stenotrophomonads, and Alcaligenes spp.) were isolated before and after TCSD exposure. Several TCS-tolerant bacteria related to Achromobacter xylosoxidans became clonally expanded during dosing. TCSD addition did not significantly affect the community profiles of susceptibility to the test biocides or antibiotics. Several microcosm isolates, as well as reference bacteria, caused clearing of particulate TCS in solid media. Incubations of consortia and isolates with particulate TCS in liquid led to putative TCS degradation by the consortia and TCS solubilization by the reference strains. Our results support the view that low-level exposure of environmental microcosms to TCS does not affect antimicrobial susceptibility and that TCS is degradable by common domestic biofilms.  相似文献   

12.
To enhance the intracellular delivery potential of plasmid DNA using nonviral vectors, we have developed thiolated gelatin nanoparticles that can release the payload in the highly reducing environment, such as in response to glutathione. Thiolated gelatin was synthesized by covalent modification of the primary amino groups of Type B gelatin using 2-iminothiolane (Traut's reagent). The degree of thiolation of the polymers ranged from 0 to 43.71 mmol of reduced sulfhydryl (SH) groups when the amount of 2-iminothiolane was increased up to 100 mg per gram of the biopolymer. Cytotoxicity evaluations carried out by the formazan (MTS) assay showed that the thiolated gelatin prepared with 20 mg and 40 mg of 2-iminothiolane (SHGel-20 and SHGel-40) per gram of gelatin had comparable cell viability profile to that of the unmodified gelatin. In vitro release studies of fluorescein isothiocyanate (FITC)-labeled dextran (mol wt. 70 000 Da), when encapsulated in gelatin and thiolated gelatin nanoparticles (150-250 nm in diameter), was found to be affected by the presence of glutathione (GSH) in the medium. The presence of GSH was found to enhance the release by about 40% in case of thiolated gelatin and about 20% in gelatin nanoparticles under similar conditions of temperature and GSH concentrations. Qualitative and quantitative analysis of transfection in NIH-3T3 murine fibroblast cells by the nanoparticles carrying plasmid DNA encoding for enhanced green fluorescent protein (EGFP-N1) was done by fluorescence confocal microscopy and fluorescence-activated cell sorting (FACS). Qualitative results showed highly efficient expression of GFP that remained stable for up to 96 h. Quantitative results from FACS showed that the thiolated gelatin nanoparticles (SHGel-20) were significantly more effective in transfecting NIH-3T3 cells than other carrier systems examined. The results of this study show that thiolated gelatin nanoparticles would serve as a biocompatible intracellular delivery system that can release the payload in a highly reducing environment.  相似文献   

13.
The purpose of this research was to study the influence of type of chitosan with different molecular weights, ie, 190 and 419 kDa, on properties of pellets prepared by extrusion/ spheronization. The formulations, consisting of acetaminophen as model drug, chitosan, microcrystalline cellulose (MCC), and dibasic calcium phosphate dihydrate with/without sodium alginate, were extruded using a twin-screw extruder and water as the granulating liquid. With 30% wt/wt MCC and no added sodium alginate, spherical pellets were produced containing low and high molecular weight chitosan at a maximum amount of 60% and 40% wt/wt, respectively. With sodium alginate (2.5% wt/wt), pellets with either type of chitosan (60% wt/wt), MCC (17.5% wt/wt), and acetaminophen (20% wt/wt) could be produced indicating an improved pelletforming ability. Type and amount of chitosan and added sodium alginate affected physical properties of pellets including size, roundness, crushing force, and drug release. Low molecular weight chitosan produced pellets with higher mean diameter, sphericity, and crushing force. Additionally, the pellets made of low molecular weight chitosan and added sodium alginate showed faster drug release in 0.1 N HCl but had slower drug release in pH 7.4 phosphate buffer. This indicated that drug release from pellets could be modified by the molecular weight of chitosan. In conclusion, the molecular weight of chitosan had a major influence on formation, physical properties, and drug release from the obtained pellets. Published: August 10, 2007  相似文献   

14.
Nanocrystalline cellulose (NCC) reinforced chitosan-based biodegradable films were prepared by solution casting. The NCC content in the films was varied from 1 to 10% (dry wt. basis). It was found that the tensile strength (TS) of the nanocomposite films with 5% (w/w) NCC content was optimum with an improvement of 26% compared to the control chitosan films. Incorporation of NCC also significantly improved barrier properties. Water vapor permeability (WVP) of the chitosan/NCC films was decreased by 27% for the optimum 5% (w/w) NCC content. Swelling studies revealed a decrease in water uptake of the NCC-reinforced chitosan films. Analyses of thermal properties showed no significant effect of NCC whereas X-ray diffraction studies confirmed the appearance of crystalline peaks in the nanocomposite films. Surface morphology of the films was investigated by scanning electron microscopy and it was found that NCC was dispersed homogenously into chitosan matrix.  相似文献   

15.
Recent concern that the increased use of triclosan (TCS) in consumer products may contribute to the emergence of antibiotic resistance has led us to examine the effects of TCS dosing on domestic-drain biofilm microcosms. TCS-containing domestic detergent (TCSD) markedly lowered biofouling at 50% (wt/vol) but was poorly effective at use levels. Long-term microcosms were established and stabilized for 6 months before one was subjected to successive 3-month exposures to TCSD at sublethal concentrations (0.2 and 0.4% [wt/vol]). Culturable bacteria were identified by 16S rDNA sequence analysis, and their susceptibilities to four biocides and six antibiotics were determined. Microcosms harbored ca. 10 log10 CFU/g of biofilm, representing at least 27 species, mainly gamma proteobacteria, and maintained dynamic stability. Viable cell counts were largely unaffected by TCSD exposure, but species diversity was decreased, as corroborated by denaturing gradient gel electrophoresis analysis. TCS susceptibilities ranged widely within bacterial groups, and TCS-tolerant strains (including aeromonads, pseudomonads, stenotrophomonads, and Alcaligenes spp.) were isolated before and after TCSD exposure. Several TCS-tolerant bacteria related to Achromobacter xylosoxidans became clonally expanded during dosing. TCSD addition did not significantly affect the community profiles of susceptibility to the test biocides or antibiotics. Several microcosm isolates, as well as reference bacteria, caused clearing of particulate TCS in solid media. Incubations of consortia and isolates with particulate TCS in liquid led to putative TCS degradation by the consortia and TCS solubilization by the reference strains. Our results support the view that low-level exposure of environmental microcosms to TCS does not affect antimicrobial susceptibility and that TCS is degradable by common domestic biofilms.  相似文献   

16.
The purpose of this research was to investigate 5-methyl-pyrrolidinone chitosan (MPC) films as carriers for buccal delivery of protein drugs. Placebo and protein-loaded MPC films were prepared by casting and were then cross-linked with tripolyphosphate at different pH conditions. Myoglobin (MHb) was chosen as the model protein because its molecular weight is under the permeability limit of the buccal mucosa. The observed characteristics like bioadhesiveness, swelling behavior, and in vitro release of MHb from loaded films furnish information on the functional behavior of these films. The results obtained show that the modulation of Mhb release was achieved only through chitosan cross-linking; the best results in release rate control were obtained by cross-linking performed at pH 6.5. Good bioadhesion properties were maintained even with high cross-linking degrees; the swelling index of MHb-loaded films at different cross-linking degrees evaluated at pH 7.4 and pH 6.4 were comparable to those of placebo films. By setting suitable tripolyphosphate cross-linking conditions for MPC films, one can control protein release without affecting bioadhesion. Published: September 1, 2006  相似文献   

17.
Chitosan is an abundantly common, naturally occurring, polysaccharide biopolymer. Its biocompatible, biodegradable, and antimicrobial properties have led to significant research toward biological applications such as drug delivery, artificial tissue scaffolds for functional tissue engineering, and wound-healing dressings. For applications such as tissue scaffolding, formation of highly porous mats of nanometer-sized fibers, such as those fabricated via electrospinning, may be quite important. Previously, strong acidic solvents and blending with synthetic polymers have been used to achieve electrospun nanofibers containing chitosan. As an alternative approach, in this work, polyethylene oxide (PEO) has been used as a template to fabricate chitosan nanofibers by electrospinning in a core-sheath geometry, with the PEO sheath serving as a template for the chitosan core. Solutions of 3 wt % chitosan (in acetic acid) and 4 wt % PEO (in water) were found to have matching rheological properties that enabled efficient core-sheath fiber formation. After removing the PEO sheath by washing with deionized water, chitosan nanofibers were obtained. Electron microscopy confirmed nanofibers of approximately 250 nm diameter with a clear core-sheath geometry before sheath removal, and chitosan nanofibers of approximately 100 nm diameter after washing. The resultant fibers were characterized with IR spectroscopy and X-ray diffraction, and the mechanical and electrical properties were evaluated.  相似文献   

18.
This report presents a new route to enhance the wet properties of chitosan-acetic-acid-salt films using microfibrillated cellulose (MFC). The enhancement makes it easier to form chitosan-acetic-acid-salt films into various shapes at room temperature in the wet state. Chitosan with MFC was compared with the well-known buffer treatment. It was observed that films containing 5 wt % MFC were visually identical to the buffered/unbuffered films without MFC. Field-emission scanning electron microscopy indicated that MFC formed a network with uniformly distributed fibrils and fibril bundles in the chitosan matrix. The addition of MFC reduced the risk of creases and deformation in the wet state because of a greater wet stiffness. The wet films containing MFC were also extensible. Although the stiffness, strength and extensibility were highest for the buffered films, the wet strength of the MFC-containing unbuffered films was sufficient for wet forming operations. The effects of MFC on the mechanical properties of the dry chitosan films were small or absent. It was concluded that the addition of MFC is an acceptable alternative to buffering for shaping chitosan films/products in the wet state. The advantages are that the "extra" processing step associated with buffering is unnecessary and that the film matrix remains more water-soluble.  相似文献   

19.
Crystallization behavior and environmental biodegradability were investigated for the films of bacterial poly(3-hydroxybutyric acid) (PHB) blends with chitin and chitosan. The blend films showed X-ray diffractive peaks that arose from the PHB crystalline component. It was suggested that the lamellar thickness of the PHB crystalline component in the blends was large enough to show detectable X-ray diffractive peaks, but this was too small to show observable melting endotherm in the DSC thermogram and the crystalline band absorption in the FT-IR spectrum. In the PHB/chitin and PHB/chitosan blends, thermal transition temperatures of PHB amorphous region observed by dynamic mechanical thermal analysis were almost the same as that of neat PHB. Both the PHB/chitin and the PHB/chitosan blend films biodegraded in an environmental medium. Several blend films showed faster biodegradation than the pure-state component polymers.  相似文献   

20.
Peng XW  Ren JL  Zhong LX  Sun RC 《Biomacromolecules》2011,12(9):3321-3329
Interest in xylan-rich hemicelluloses (XH) film is growing, and efforts have been made to prepare XH films with improved mechanical properties. This work described an effective approach to produce nanocomposite films with enhanced mechanical properties by incorporation of cellulose nanofibers (CNFs) into XH. Aqueous dispersions of XH (64-75 wt %), sorbitol (16-25 wt %), and CNF (0-20 wt %) were cast at a temperature of 23 °C and 50% relative humidity. The surface morphology of the films was revealed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). The thermal properties and crystal structure of the films were evaluated by thermal analysis (TG) and X-ray diffraction (XRD). The surface of XH films with and without CNF was composed primarily of nanonodules, and CNFs were embedded in the XH matrix. Freeze-dried XH powder was amorphous, whereas the films with and without CNF showed a distinct peak at around 2θ = 18°, which suggested that XH molecules aggregated or reordered in the casting solution or during water evaporation. Furthermore, the nanocomposite films had improved thermal stability. XH film with 25 wt % plasticizer (sorbitol, based on dry XH weight) showed poor mechanical properties, whereas incorporation of CNF (5-20 wt %, based on the total dry mixture) into the film resulted in enhanced mechanical properties due to the high aspect ratio and mechanical strength of CNF and strong interactions between CNF and XH matrix. This effective method makes it possible to produce hemicellulose-based biomaterials of high quality.  相似文献   

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