壳聚糖作为牙周引导性组织再生屏障膜的实验研究

目的制备壳聚糖屏障膜,观察其微观结构,并观察在体外培养条件下壳聚糖膜对牙周膜细胞增殖的影响。方法采用相分离法制备壳聚糖膜,利用扫描电镜观察微观结构,MTT法评价壳聚糖膜对牙周膜细胞体外增殖的影响。结果于-5℃将20g/L的壳聚糖液冷冻干燥可制备出孔隙率>90%,孔隙直径介于50μm与100μm之间的壳聚糖膜,这种壳聚糖膜具有促进牙周膜细胞体外增殖的效应。结论壳聚糖膜适合作为引导性组织再生屏障膜。     

洛美沙星壳聚糖口腔溃疡膜的制备及含量测定方法的建立

目的 :研制洛美沙星壳聚糖口腔溃疡膜 ,并建立其含量测定方法。方法 :以壳聚糖、甘油、明胶为辅料制备洛美沙星壳聚糖口腔溃疡膜 ,建立了含量测定方法。结果 :此品制备工艺可行。结论 :此品适用于临床。     

不同取代度的羟丙基壳聚糖生物降解性研究

目的：研究不同取代度的羟丙基壳聚糖膜的生物相容性及其取代度对生物降解性的影响。方法：通过体外降解及动物体内实验研究其降解性和生物相容性。结果：不同取代度的羟丙基壳聚糖均具有较好的生物相容性；随着取代度的增加，羟丙基壳聚糖膜的降解速度加快；并且溶茵酶对羟丙基壳聚糖膜的生物降解性有促进作用。结论：羟丙基壳聚糖膜具有良好的生物相容性。通过控制取代度，可以得到不同要求的羟丙基壳聚糖。     

替硝唑壳聚糖口腔膜剂的研制与临床疗效

目的制备替硝唑壳聚糖口腔膜剂 ,并应用于临床。方法以壳聚糖、卡波普、羧甲基纤维素为成膜材料制备替硝唑壳聚糖口腔膜剂 ,建立质量标准 ,并对其进行疗效观察。结果该膜剂制备工艺简单 ,质量控制方法可靠 ,临床疗效确切 ,总有效率达 96 .5 %。结论此品可试用于临床     

药用壳聚糖生物降解膜的研制

用不同性能的壳聚糖制膜，通过体外降解、酶解及动物试验，研究其降解性和生物相容性。结果表明，壳聚糖是一种很有发展前景的药用天然膜材料。     

壳聚糖-甘油膜的制备和表征

目的制备壳聚糖-甘油膜，用于解决术后粘连问题。方法通过将壳聚糖和甘油共混，充分利用两者的优点，达到生理功能的协同增效及物化性能的改善。结果实验表明，壳聚糖-甘油膜在湿态下仍具有良好的力学性能，在实际应用中能够承受缝合强度，其最大拉伸强度达到17．3MPa，断裂伸长率达到99％，并且壳聚糖-甘油膜具有良好的吸水率，最大吸水率为123％，在实际应用中减少了创伤面的积液。结论采用溶致沉淀法制备壳聚糖-甘油膜，大大节省了制备时间。甘油的加入有利于改善膜的柔韧性，满足实际应用需要，壳聚糖-甘油膜无色透明、表面光洁、无气泡、手感柔韧性较好。该膜经动物体内植入实验，与对照组相比，有明显的防粘连效果。     

磺胺嘧啶银壳聚糖膜的制备与质量控制

目的制备磺胺嘧啶银壳聚糖烧伤复层膜,建立其质量控制方法。方法以壳聚糖为外膜、磺胺嘧啶银壳聚糖为内膜制备烧伤复层膜;采用永停滴定法滴定磺胺嘧啶银含量。结果所制复层膜光滑、稳定、粘附力强、稳定性好,磺胺嘧啶银平均回收率为97.41%,RSD为1.09%。结论本制备工艺合理,含量测定方法简便,质量稳定可控。     

复方骨形成蛋白牙槽生物黏附膜的制备及质量控制

目的：制备复方骨形成蛋白牙槽生物黏附膜，并对其质量控制和体外释放进行研究。方法：以水溶性壳聚糖、聚乙烯醇（PVA）、甘油、明胶、海藻酸钠等作为膜材制备空白膜，利用正交设计对处方工艺进行优选。将凝血酶载入水溶性壳聚糖制成固定化凝血酶，与骨形成蛋白、头孢哌酮钠混合后加至空白膜基质中，制成复方骨形成蛋白牙槽生物黏附膜。通过定性、检查、定量试验制定其质量控制，并考察其释放行为。结果：水溶性壳聚糖的浓度对膜剂性能及主要控制指标的影响较为显著。水溶性壳聚糖经海藻酸钠交联后，药物在0．9％氯化钠溶液中溶解释放时间可达3—9h。结论：复方骨形成蛋白牙槽生物黏附膜处方组成合理，制备工艺可行，质量控制方法准确、可靠，可作为本品的质量控制方法，体外释放基本符合生物黏附膜要求。     

碳纳米管对镁合金基体上钙磷/壳聚糖膜层释药性能的影响

目的:研究碳纳米管对镁合金基体上钙磷/壳聚糖膜层负载的庆大霉素在模拟体液中释放性能的影响。方法:采用浸渍法分别将庆大霉素负载在钙磷/壳聚糖膜层和钙磷/壳聚糖/碳纳米管膜层中,采用紫外分光光度法测定庆大霉素在模拟体液中的释放浓度。结果:镁合金基体上钙磷/壳聚糖膜层负载碳纳米管后,膜层中庆大霉素负载量增加、庆大霉素释放速度降低。结论:碳纳米管有效改善了镁合金基钙磷/壳聚糖骨材料的释药性能。     

壳聚糖-聚乳酸及壳聚糖-聚(R)-3-羟基丁酸甲酯共混膜的制备及评价

用流延法制备壳聚糖与聚乳酸或聚(R)-3-羟基丁酸甲酯共混膜。壳聚糖-聚乳酸(1∶1,w/w)和壳聚糖-聚(R)-3-羟基丁酸甲酯(1∶1,w/w)共混膜的抗拉强度为(25.39±1.63)和(23.49±0.43)MPa,吸水率为(32.65±2.41)%和(33.72±3.11)%。该壳聚糖-聚乳酸膜在人工组织液中浸泡45 d后,降解率为(32.26±0.56)%,提示其可诱导新组织再生。     

The influence of multivalent phosphate structure on the properties of ionically cross-linked chitosan films for controlled drug release.

The aim of this paper was to investigate the electrostatic interactions between multivalent phosphates (phosphate (Phos), pyrophosphate (Pyro) and tripolyphosphate (TPP)) and chitosan, as well as the influence of electrostatic interactions on the properties of chitosan films ionically cross-linked by the above mentioned phosphates. The charge number of Phos was too low to interact with chitosan, while Pyro and TPP with more negative charges showed a significant ability to ionically cross-link chitosan. Solution pH played an important role on the charge numbers carried by Pyro, TPP and chitosan, especially for Pyro/chitosan. For instance, at pH less than 2.0 the interaction between Pyro and chitosan disappeared, while for TPP/chitosan even in solutions at pH less than 0.5 it still existed. Media pH and ionic strength also had a significant influence on the properties of cross-linked chitosan film with multivalent phosphates. Usually these films swelled and drug was released quickly in acidic conditions (such as in simulated gastric fluid) while under neutral conditions (such as in simulated intestinal fluid) they remained in a shrinkage state and drug was released slowly. Compared to TPP/chitosan films, Pyro/chitosan films exhibited much better pH-sensitive swelling and controlled release properties due to their relatively weak electrostatic interaction. The same reasoning was used to explain the significant acceleration of Pyro/chitosan film swelling and model drug release observed on adding sodium chloride. These films may be promising for site-specific drug delivery in the stomach.     

Preparation and Evaluation of Transdermal Drug Delivery System of Etoricoxib Using Modified Chitosan

In the present investigation chitosan has been chemically modified by treating with two different aldehydes like acetaldehyde and propionaldehyde to form Schiff’s bases. Schiff’s bases of chitosan with acetaldehyde and propionaldehyde were named as polymer A and polymer B, respectively. Fourier Transform Infra Red (FTIR) spectral data have confirmed the reaction carried out on chitosan. Drug free polymeric films of chitosan, chemically modified chitosan and chitosan/hydroxypropylmethylcellulose blend were prepared and evaluated for various physicochemical characters. Further, the films were incorporated with anti-inflammatory drug, etoricoxib using glycerol as plasticizer. The drug loaded films were cross-linked with sodium citrate and studied for permeation characteristics across dialysis membrane and rat skin. All the films were evaluated for bursting strength, swelling index, moisture uptake, thickness uniformity, drug content uniformity, tensile strength, percent elongation at break, percent flatness, water vapour transmission rate and in vitro drug permeation study.     

Physicochemical and cell adhesion properties of chitosan films prepared from sugar and phosphate-containing solutions.

This work was aimed at investigating a series of chitosan films obtained from chitosan, chitosan-phosphate, chitosan-phosphate-D-(+)raffinose or chitosan-phosphate-D-(+)sucrose solutions to preliminarily select a suitable biomaterial for developing a cell substrate for tissue engineering. The prepared films were characterized in terms of physicochemical properties (FT-IR, XRD, optical microscopy, wettability, water absorption, and tensile stress) and effects on proliferation of different types of human cells (endothelial, HUVEC; fibroblast, WI-38). The obtained results indicated that the presence of sucrose or raffinose at high concentration along with phosphate salts in the chitosan film-forming solution affords smooth, amorphous and highly hydrophilic materials in the form of soft and elastic film with optimal cytocompatibility. Owing to improved physicochemical and mechanical properties as well as affinity for differentiated human cells, these novel chitosan films appear as promising candidate biomaterials for tissue regeneration and repair. The major finding is the possibility to improve the biocompatibility of chitosan films by simply modifying their solid state characteristics.     

An investigation into the characteristics of chitosan/Kollicoat SR30D free films for colonic drug delivery

The purpose of the study was to establish the physico-mechanical, digestibility, permeability and swelling properties of chitosan/Kollicoat SR30D films as potential coatings for colonic drug delivery. Free films containing different ratios of chitosan to Kollicoat SR30D were prepared by casting/solvent evaporation method. The resultant mixed films were characterized in terms of puncture strength and elongation (%), glass transition temperature, swellability, polymer miscibility, permeability, and digestibility under different media. The mixed films possessed good mechanical properties, which could be used as film-coating materials for drug delivery. The extent of digestion was directly proportional to the amount of chitosan present within the film. No apparent miscibility was detected between the chitosan and Kollicoat SR30D, regardless of the film composition. The films were found to be susceptible to digestion by bacterial or β-glucosidase enzymes in simulated colonic fluid (SCF). The SCF with rat cecal bacterial enzymes had a more profound hydrolytic activity than that with β-glucosidase enzyme for the digestion of chitosan within the mixed films. Overall, the results indicated that such chitosan/Kollicoat SR30D films had potential as a coating system for drug delivery to the colon.     

Preparation and characterization of free mixed-film of pectin/chitosan/Eudragit RS intended for sigmoidal drug delivery.

Polyelectrolyte complex (PEC) film between pectin as an anionic polyelectrolyte and chitosan as a cationic species was prepared by blending two polymer solutions at weight ratio of 2:1 and then solvent casting method. Besides pectin/chitosan PEC film, Eudragit RS, pectin/Eudragit RS and pectin/chitosan/Eudragit RS films were also prepared by aforementioned method. In mixed-film formulations, a fixed weight ratio of 1:5 of pectin or pectin/chitosan complex to Eudragit RS was used. Characterizations of pectin/chitosan interaction in solution were investigated by turbidity and viscosity measurement and in the solid state by Fourier transform infrared (FTIR) spectroscopy, wide angle X-ray diffraction (WAXRD) and thermogravimetric analysis (TGA). It was observed that the swelling profile of pectin/chitosan film was pH-dependent and its swelling ratio in phosphate buffer solution (PBS) pH 7.4 was about 2.5-fold higher than that of PBS pH 6.0. Formulation containing only pectin/chitosan could not protect free film from high swelling in the aqueous media, therefore, Eudragit RS as a water-insoluble polymer must be included in the mixed-film. The formation of PEC between pectin and chitosan resulted in a decrease in the crystallinity and thermal stability caused by the interactions between polyions. Drug permeation or diffusion studies were carried out using Plexiglas diffusion cell consisting of donor and acceptor compartments. Theophylline was selected as a model drug to measure permeability coefficient. Drug permeation through pectin/chitosan/Eudragit RS showed a sigmoidal pattern; whereas drug diffusion through pectin/Eudragit RS and Eudragit RS films followed a linear characteristic. The drug permeation through the ternary mixed-film showed a burst release upon exposure to PBS pH 6.0. This mixed-film formulation showed the potential for sigmoidal drug delivery with an initial, controllable slow release followed by a burst release immediately after the change in pH. The burst drug permeation might possibly be due to change in film's porosity.     

Optimization of chitosan film as a substitute for animal and human epidermal sheets for in vitro permeation of polar and non polar drugs

The present investigation is aimed at preparing chitosan films capable of simulating the flux of modal drugs, 5-fluorouracil (5-FU) and indomethacin (INDO), across rat, rabbit and human cadaver epidermal sheets. Application of statistical design revealed that the concentration of chitosan, crosslinking time and concentration of crosslinking agent significantly influenced the in vitro flux of 5-FU and INDO across chitosan films. Multiple linear regression revealed a linear influence of all these active variables on 5-FU and INDO flux. It was deduced from atomic absorption spectroscopic analyses, DSC and IR spectroscopic data that 5% (m/V) sodium tripolyphosphate (NaTPP) produced optimum crosslinking of chitosan films. The in vitro permeation of both 5-FU and INDO across optimized film formulations was found to be comparable to that obtained across rat, rabbit and human epidermal sheets. These results indicate that optimized chitosan films have a potential to be developed as a substitute for animal and human cadaver epidermal sheets for preliminary in vitro permeation studies.     

Hybrid films from blends of chitosan and egg phosphatidylcholine for localized delivery of paclitaxel

Chitosan and egg phosphatidylcholine (ePC) were used as a unique combination to prepare composite films for localized drug delivery. In comparison to other phospholipids analyzed, ePC was found to produce chitosan-based films with minimal swelling and a high degree of stability. The properties of the chitosan-ePC films were characterized and found to be dependent on the ratio of chitosan:ePC present. FTIR analysis of chitosan-ePC films revealed that their high stability may be attributed to interactions present between these two biomaterials. In vitro evaluation of the cytotoxicity and protein adsorption properties of the films were used to provide a preliminary indication of their biocompatibility. The chitosan-ePC film was also evaluated as a matrix for the localized delivery of the anti-cancer agent, paclitaxel. Nanoparticles containing paclitaxel were dispersed throughout the chitosan-ePC film to result in a drug:material ratio of 1:8 (wt/wt). The film was found to provide a sustained release of paclitaxel over a 4-month period in biologically relevant media. The biological activity of paclitaxel loaded in the chitosan-ePC film was confirmed in SKOV-3 human ovarian cancer cells.     

Polymorph Farming of Acetaminophen and Sulfathiazole on a Chip

Purpose The aim of this paper is to understand at a given temperature (1) the role of template films, the droplet volume of a saturated sulfathiazole aqueous solution and the solvent on polymorph screening of sulfathiazole on a silicon wafer, and (2) the effect of template films on the acetaminophen crystal face at the template-crystal interface.Materials and Methods Template Effect: Spun cast template films of non-annealed chitosan and annealed chitosan at 140°C on silicon wafers were prepared. A 0.01-cm³ saturated sulfathiazole aqueous solution droplets were deposited on both kinds of chitosan film. Sulfathiazole crystals were produced on those films by evaporation at 25°C. Volume Effect: Different droplet volumes of a saturated sulfathiazole aqueous solution ranging from 0.01 to 0.14 to 2.7 cm³ were deposited on non-annealed chitosan films. Sulfathiazole crystals were generated on those films by evaporation at 25°C. Solvent Effect: 0.01 cm³ saturated sulfathiazole methanol solution droplets were deposited on non-annealed chitosan films and sulfathiazole crystals were formed on those films by evaporation at 25°C. The formation pathways of different sulfathiazole crystal polymorphs of the above mentioned effects were analyzed and verified by systematic studies. Template-crystal Interfacial Study: Millimeter-sized acetaminophen crystals were successfully grown on non-annealed chlorosulfonated poly(ethylene) (PE-Chl) and chitosan template films by cooling the saturated acetaminophen aqueous solution from 50 to 25°C in which those template films were immersed. The bonding energies for specific carbons collected by electron spectroscopy for chemical analysis (ESCA) at the acetaminophen crystal surface, together with the molecular interactions between acetaminophen and PE-Chl and between acetaminophen and chitosan in separately prepared solid dispersion film samples detected by Fourier transformed infrared (FTIR) spectroscopy, proved to be useful for identifying the crystal face of acetaminophen essential for its specific intermolecular interactions at the template-crystal interface.Results Thermodynamically metastable sulfathiazole Form I crystals were reproducibly obtained on the non-annealed chitosan films whereas the stable sulfathiazole Form III crystals were repeatedly formed on the annealed chitosan films. Droplet volumes and solvents were also found responsible for the polymorphic outcome of sulfathiazole in the kinetically driven area of two overlapping metastable zones from two competing polymorphs of Form I and Form III. Thermodynamically stable sulfathiazole Form III crystals were formed on the non-annealed chitosan films instead when the droplet volumes of a saturated sulfathiazole aqueous solution were increased from 0.01 to 0.14 cm³ and 2.7 cm³. When the solvent was changed from water to methanol, the thermodynamically stable sulfathiazole Form III crystals were again observed on the non-annealed chitosan films even from the 0.01 cm³ saturated sulfathiazole methanol solution droplets.Conclusions Template surfaces were thought to provide specific functional groups to either change the energy barrier for the nuclei formation of the thermodynamically metastable Form I or alter the droplet contact angle and the droplet surface area which was related to the droplet evaporation time. The evaporation time determines the amount of time available for the polymorphic transformation from Form I to Form III. Apparently, droplet volumes could also determine the amount of time needed to reach supersaturation and the amount of time available for a polymorphic transformation from Form I to Form III. In addition, the molecular conformation and viscosity of solvents such as methanol might alter the original nucleation kinetics in water and lead to a more rapid polymorphic transformation from Form I to Form III. Template films of PE-Chl and chitosan were found to be critical for determining the face of a millimeter-sized acetaminophen crystal at the template-crystal interface. The idea of performing polymorph screening on the template film deposited on a chip has opened up a new doorway to examine the roles of: (1) various kinds of drug carrier in the form of a template film, (2) the droplet volume of a saturated solution, and (3) the type of solvent used, in polymorphic control. Growing millimeter-sized crystals directly on the chip of template has also provided a convenient technology enabling platform for examining the crystal-template interface by solid-state characterization techniques such as ESCA.     

Development and characterization of biodegradable chitosan films for local delivery of paclitaxel

Intratumoral and local drug delivery strategies have gained momentum recently as a promising modality in cancer therapy. In order to deliver paclitaxel at the tumor site in therapeutically relevant concentrations, chitosan films were fabricated. Paclitaxel could be loaded at 31% wt/wt in films, which were translucent and flexible. Physicochemical characterization of paclitaxel via thermal, spectroscopic, x-ray diffraction, and electron microscopy techniques revealed information on solid-state properties of paclitaxel as well as chitosan in films. While chitosan was in amorphous form, paclitaxel seemed to be present in both amorphous and crystalline forms in film. The polymeric dispersion of paclitaxel in poloxamer formed fibrous structures generating discontinuities in the film matrix, thereby leading to the introduction of perturbations in the packing arrangement of polymer chains. These films released only 10% to 15% of loaded paclitaxel by a burst effect under in vitro testing conditions, with lysozyme having no effect on the release. However, films softened after implantation in mice and lost integrity over time. The implantable delivery system is not only biodegradable but also well tolerated in vivo and hence, biocompatible as revealed by histological studies. The lack of formulation-induced local inflammatory responses of paclitaxel chitosan films suggests a new paradigm for localized chemotherapy based on implantable systems.     

Biphasic drug release: the permeability of films containing pectin, chitosan and HPMC

The permeabilities of mixed films of pectin/chitosan/HPMC have been studied to assess their value in producing a dosage form with biphasic drug release characteristics. The inclusion of chitosan enhanced the properties of the films, rendering them stable at all physiological pH values. Pectin/HPMC films were soluble at pH values above 3.0. All pectin/chitosan/HPMC films were permeable to a model drug, paracetamol. HPMC initially increased the permeability of the films and subsequently reduced it at higher concentrations. The minimum permeability was obtained at pH 3 and at an HPMC level of 5% where the potential for polyelectrolyte complex formation between pectin and chitosan exists. The permeabilities of the films increased when they were exposed to pectinolytic enzymes, a system designed to mimic conditions in the colon. The film formulation thus show the potential for biphasic delivery with an initial, controllable slow phase that can be manipulated by changes in the formulation followed by a faster phase under conditions pertaining in the colon.