Preparation,Characterization of Hydrophobic Drug in Combine Loaded Chitosan/Cyclodextrin/Trisodium Citrate Nanoparticles and in vitro Release Study

Chitosan/cyclodextrin/trisodium citrate(CS/CD/TSC) nanoparticles with ibuprofen(IBU) loaded were prepared via the ionic cross-linking method, with trisodium citrate selected as the cross-linking agent. The drug-loading capacity, particle size, zeta potential and surface morphology of the obtained nanoparticles were investigated. The results show a good drug-loading capacity. The prepared nanoparticles were spherical in shape with an average size of 293.7 nm and a zeta potential of +30.72 mV. The in vitro release studies show that the controlled release of IBU from the nanoparticles was followed. The drug release from CS/β-CD/TSC nanoparticles followed non-Fickian or anomalous diffusion.     

布洛芬插层类水滑石/淀粉凝胶复合物的制备及缓释行为

为设计新型布洛芬缓释体系提供实验依据,以氯化镁、氯化铝、布洛芬(IBU)及淀粉等为原料,采取共沉淀-焙烧还原法及冷冻-解冻法,制备了层状双氢氧化物-布洛芬插层复合物(LDH-IBU)、淀粉凝胶-布洛芬复合物(淀粉凝胶-IBU)及层状双氢氧化物/淀粉凝胶-布洛芬插层复合物(LDH/淀粉凝胶-IBU)。 通过傅里叶红外光谱仪(FT-IR)、X射线衍射仪(XRD)表征了上述3种复合物的结构,并研究了它们在模拟人体环境条件下的缓释性能。 结果表明,3种复合物中的IBU在不同的缓释介质中都具有一定的缓释效果,复合物释放速率大小为:LDH/淀粉凝胶-IBU>LDH-IBU>淀粉凝胶-IBU;在pH值为6.6和7.4以及0.9%生理盐水3种缓冲介质中释放速率依次减小。 释放动力学均符合准一级动力学方程。     

聚L-谷氨酸担载胰岛素口服微球的制备与评价

以聚L-谷氨酸为载体材料, 采用无水乳液法制备了口服胰岛素微球, 微球直径在5~20 μm, 载药质量分数为5%~9%. 载药微球具有良好的pH敏感释放行为, 在胃模拟液中2 h释放量约为5%, 在肠道模拟液中2 h释放90%以上. 考察聚合物分子量、溶液浓度、理论投药量及混合材料对微球释放行为的影响.     

Preparation and characterization of a novel pH-sensitive ion exchange resin

Methylacrylic acid/styrene cross-linked with divinylbenzene is a novel pH-sensitive ion exchange resin. Microspheres of this resin were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The microspheres showed a pulsatile swelling behavior when the pH of the media changed. The pH-sensitive microspheres were loaded with salbutamol sulfate and the drug-release characteristics were studied under both simulated gastric and intestinal pH conditions. The results obtained showed that the drug release also depended on the pH of the release media.     

Yolk‐Shell Porous Microspheres of Calcium Phosphate Prepared by Using Calcium L‐Lactate and Adenosine 5′‐Triphosphate Disodium Salt: Application in Protein/Drug Delivery

A facile and environmentally friendly approach has been developed to prepare yolk‐shell porous microspheres of calcium phosphate by using calcium L ‐lactate pentahydrate (CL) as the calcium source and adenosine 5′‐triphosphate disodium salt (ATP) as the phosphate source through the microwave‐assisted hydrothermal method. The effects of the concentration of CL, the microwave hydrothermal temperature, and the time on the morphology and crystal phase of the product are investigated. The possible formation mechanism of yolk‐shell porous microspheres of calcium phosphate is proposed. Hemoglobin from bovine red cells (Hb) and ibuprofen (IBU) are used to explore the application potential of yolk‐shell porous microspheres of calcium phosphate in protein/drug loading and delivery. The experimental results indicate that the as‐prepared yolk‐shell porous microspheres of calcium phosphate have relatively high protein/drug loading capacity, sustained protein/drug release, favorable pH‐responsive release behavior, and a high biocompatibility in the cytotoxicity test. Therefore, the yolk‐shell porous microspheres of calcium phosphate have promising applications in various biomedical fields such as protein/drug delivery.     

Flow Through Diffusion Cell Method: A Better Approach to Study Drug Release Behavior as Compared to Traditional Dissolution Test Method

Co‐polymeric hydrogels consisting of N‐vinyl‐2‐pyrrolidone (NVP) and acrylic acid (AAc) were synthesized and evaluated for release of a model drug, i.e., vitamin B₁₂. Release studies in simulated gastric fluid (pH 1.2) and intestinal fluid (pH 7.4), at 37°C, showed the hydrogels to be pH sensitive. An in vitro release study by ‘traditional dissolution test’ (TDT) showed that percent drug released from the hydrogel was nearly 8.6±2.1 and 83.2±4.8 in the media of pH 1.2 and 6.8, respectively. However, in order to incorporate in vivo GI conditions such as acidic pH and high water content in the stomach, low water content and the presence of a semi–solid mass in the large intestine, a new test model, called flow through diffusion cell (FTDC) was also used. The two approaches yielded almost different release profiles. The gels were characterized by thermogravimetric analysis and FTIR spectroscopy.     

Chitosan based hydrogel microspheres as drug carriers

Chitosan/tripolyphosphate (CHIT/TPP) and chitosan/tripolyphosphate/chondroitin sulfate (CHIT/TPP/CHS) core-shell type microspheres were prepared by polyelectrolyte complexation in order to develop a biocompatible matrix for drug delivery. The continual method using a multi-loop reactor under sterile conditions was applied for microsphere preparation. All the types of microspheres produced were spherical in shape and had a porous structure. The mechanical resistance of the microspheres increased in the presence of CHS as the second polyanion, which toughened the microsphere shell structure. For a drug release application, the process of microsphere preparation was modified by dissolving ofloxacin (OFL), the fluoroquinolone antibiotic, in CHIT solution before complex formation. This study shows the difference in OFL release comparing the microspheres CHIT/TPP and CHIT/TPP/CHS and implies the potential to control this process.     

A spheres-in-sphere structure for improving protein-loading poly (lactide-co-glycolide) microspheres

In present study, protein loaded poly (lactide-co-glycolide)/chitosan microspheres (PLGA/CS MSs) with spheres-in-sphere structure were prepared in order to weaken the burst release of protein from PLGA microspheres (PLGA MSs) and to buffer acidic micro-milieu. The PLGA MSs and PLGA/CS MSs were characterized in terms of their size distribution, morphology, drug-loading rate, zeta potential and physical-chemical properties. The incubation experiments of PLGA MSs and PLGA/CS MSs were manipulated in PBS solution at pH 7.4, 37 °C to monitor the release of BSA and the vehicles degradation. The release kinetic of BSA was illuminated mainly based on the degradation processes of the matrices. External CS crusts were proved to strikingly improve the release kinetic of the model protein by reducing initial burst release and extending continuous release while acting as a diffusion barrier. Moreover, using PLGA/CS MSs could avoid the decrease of pH value resulted from the acidic products of PLGA MSs because of the effective buffer action of the basic groups in CS. The results demonstrated that the spheres-in-sphere structure is an effective way to control the initial burst release of protein and to overcome the acidic problem of protein-loading PLGA MSs.     

CS/TPP纳米微胶囊的制备及其载药性能

利用离子凝胶法, 以三聚磷酸钠(TPP)为交联剂, 由壳聚糖(CS)制备了CS/TPP纳米微胶囊. 用红外光谱仪、扫描电镜和粒径分析仪进行了表征, 并以牛血清蛋白(BSA)作为模型药物, 考察了所制备的CS/TPP纳米微胶囊的包载和缓释性能. 结果表明, CS/TPP纳米微胶囊的红外光谱相对于CS和TPP的红外光谱发生了很大变化, 说明CS和TPP通过正负电荷吸引聚合成囊; 粒径分析表明, 离子凝胶法可以得到粒径约430 nm的均匀分散的壳聚糖纳米微胶囊, 经冷冻干燥后粒径变为300 nm左右; 微胶囊包封率最高可达79.74%, 模型药物的持续释放时间可达7 d以上.     

Dynamic Release of Riboflavin from Ethyl Cellulose Coated Barium Alginate Beads for Gastrointestinal Drug Delivery: An in vitro Study

The present work describes the dynamic release of model drug riboflavin form uncoated and ethyl cellulose coated barium alginate beads in the media of continuous varying pH at the physiological temperature 37°C. The drug release behavior has been studied in the simulating gastric fluid (SGF, pH 1.2) for 0–2 h and then in the simulating intestinal fluid (SIF pH 6.8) for 2–48 h. In addition to the traditional dissolution test (TDT, the dynamic release has also been studied by a newly developed method, called ‘flow through diffusion cell’ (FTDC). The release profiles, obtained by using these two methods have been found to differ appreciably from each other. Moreover, the nature of the solid mass surrounding the beads in the FTDC method also influences the release behavior of beads. The uncoated beads demonstrated faster drug release of drug in the medium of lower pH (i.e., 1.2) as compared to that in the medium of pH 6.8 and the release process was found to be diffusion controlled.     

Ultrasound-Triggered Release of Ibuprofen from a Chitosan-Mesoporous Silica Composite- a Novel Approach for Controlled Drug Release

Summary: In this work, an attempt was made to synthesize a novel Chitosan-Mesoporous silica (CS-MS) hybrid composite to design a drug delivery system based on ultrasound triggered stimuli-responsive smart release. The in-vitro drug release properties of both the Mesoporous Silica (MS) and Chitosan (CS) hybrids were investigated. Ibuprofen (Ibu) was used as a model drug. The results from powder X-Ray diffraction (XRD) patterns, and BET N₂ adsorption isotherms exhibited that MS can accommodate drug molecules into the lumen of the channels and pores. Drug release, stimulated by temperature and pH of the release media was also investigated. We studied the Ultrasound (US) triggered release of Ibu in a simulated body fluid (pH 7.4). The results exhibited that US can be used as a non-invasive technique for drug release from polymeric materials. The enhancing effect of ultrasound on drug release is due to the Cavitation effect, without causing any significant destruction on the polymer morphology.     

Controlled and targeted delivery of diclofenac sodium to the intestine from pH-Responsive chitosan/poly(vinyl alcohol) interpenetrating polymeric network hydrogels

pH-Responsive hydrogels comprised of chitosan and poly(vinyl alcohol) were explored for the controlled delivery of diclofenac sodium (DS) to the intestine. To regulate the drug delivery, preformed solid inclusion complex of DS with ß-cyclodextrin (ß-CD) was added into the hydrogels. Negligible drug release was observed in the simulated gastric fluid and sustained release in the intestinal fluid. The preliminary kinetics revealed that the drug release follows anomalous transport mechanism which is influenced by the presence of ß-CD. The pH-specific release behavior of these hydrogels suggests them to be ideal candidates for oral controlled delivery of DS to the intestine.     

PEC films prepared from Chitosan-Alginate coacervates

Chitosan-alginate polyelectrolyte complex (PEC) have been prepared in situ in beads and microspheres. This study examines the preparation of suitable chitosan-alginate coacervates for casting into homogeneous PEC films for potential applications in packaging, controlled release systems and wound dressings. Coacervation between chitosan and alginate was rapid, but the rate may be controlled with the addition of water miscible organic solvents. Compared with ethanol and PEG200, acetone was the more promising solvent moderator. Suspensions of fine, uniformly dispersed coacervates were produced by a dropwise addition of 0.25% w/v chitosan solution (solvent: 1: 1 v/v of 2% acetic acid and acetone) into 0.25% w/v sodium alginate solution in water under rapid agitation. The PEC films were transparent and flexible. They exhibited high permeability to water vapor, but resisted complete dissolution in 0.1 M HCI, distilled water and pH 7.4 phosphate buffer solution. Microscopic heterogeneity in the films could be reduced by immersion in aqueous media, but this was accompanied by modifications in the thickness, permeability and mechanical property of the films.     

Preparation and evaluation of nano-hydroxyapatite/poly(styrene-divinylbenzene) porous microsphere for aspirin carrier

A novel vehicle for the delivery of aspirin (ASA) was prepared from porous nano-hydroxyapatite/poly(styrene-divinylbenzene) [nano-HAP/P(St-DVB)] composite microspheres by grafting nano-HAP [Ca10(PO4)6(OH)2] onto porous P(St-DVB) microspheres. Four types of porous composite microspheres were prepared, each with different nano-HAP contents. The ASA-loaded composite microspheres prepared with 10% and 15% nano-HAP (mass ratio) exhibited excellent buoyancy with relatively short instantaneous floating time (within 10 min) and a long sustained floating time (12 h) in simulated gastric juice. They also offered good sustained release of ASA (up to 8 h). Furthermore, these composite microspheres displayed good buffering capacity that prevented the buildup of acidity caused by hydrolysis of ASA, keeping the pH of gastric juice within the normal range (pH 0.9 to 1.5). The results showed that porous nano-HAP/P(St-DVB) composite microspheres prepared with 10% and 15% nano-HAP could be used as a novel drug carrier for ASA, providing a sustained release dose without leading to stomach irritation, a side effect that is often associated with ASA medication.     

盐溶液调控海藻酸钙微球中的自由羧酸根及其对阿霉素的装载和释放行为研究

采用膜乳化-凝胶化法制备了粒径窄分布的海藻酸钙微球.用不同浓度的氯化钠溶液处理微球来调控微球中的自由羧酸根的含量.用原子吸收光谱和红外光谱表征了微球中钙、钠离子以及化学基团的变化,证明盐处理后海藻酸钙微球内发生了钠离子置换钙离子的过程,海藻酸中的羧酸根由螯合态转变为自由态.用盐处理后的微球吸附带正电荷的小分子抗癌药物阿霉素的能力大大提高,其中用浓度1.8%的氯化钠溶液处理后的微球载药量达到1310μg/mg,是未处理微球的10倍.负载药物的微球具有pH敏感的释放行为,在pH5.5的PBS溶液中的释放速率和释放量显著大于在pH 7.4的PBS溶液中.     

麦饭石含量对载药复合凝胶小球释药性能的影响

以瓜尔胶-g-聚丙烯酸/麦饭石复合水凝胶(GG-g-PAA/MS)和海藻酸钠(SA)为原料,双氯芬酸钠(DS)为模拟药物,采用离子凝胶法制备了载药复合凝胶小球,考察了pH敏感性以及MS含量对复合凝胶小球的包封率、载药率、溶胀性和药物释放行为的影响.结果表明:凝胶小球具有明显的pH敏感性,在不同pH介质中溶胀率和释放速率...     

Electrokinetically-controlled RNA-DNA hybridization assay for foodborne pathogens

Chitosan microspheres were prepared by an emulsion crosslinking method using glutaraldehyde as the cross-linker. Two auxins were dissolved in ethyl benzoate and encapsulated into the microspheres. The best encapsulation efficiency for naphthalene-1-acetic acid and indole-3-acetic acid, respectively, are 68% and 56% and depends on the selection of the appropriate extent of crosslinker, crosslinking time, and the ratio of the oil/water phase. The microspheres were characterized by FTIR spectroscopy. Differential scanning calorimetry was applied to study the thermal stabilities, and scanning electron microscopy to investigate the morphology of the loaded microspheres. In-vitro release studies performed in buffered aqueous methanol at pH 7.4 indicated that the cumulative release rate of the auxins from the particles reaches a maximum (60%) after about 120?h. The release rate in water is higher than the one in methanol. Based on data for the correlation coefficient it is concluded that the drug release is controlled by a diffusion mechanism that follows a super Case-II transport scheme.

基于HPMCP包覆介孔SBA-15的pH敏感药物缓释系统

以肠溶性包衣材料羟丙甲纤维素邻苯二甲酸酯(HPMCP)为原料,在负载法莫替丁(Famo)的SBA-15药片表面包覆聚合物膜,成功制备了一种新型的pH敏感药物缓释系统, 并考察了此缓释系统在不同pH释放环境中的释放行为. 结果表明: 在模拟胃液中(SGF, pH=1.2),HPMCP能致密包覆在药片表面,从而明显延缓Famo的释放速度;而在模拟肠液中(SIF, pH=7.5),HPMCP能够迅速溶于缓释溶液中,因而对Famo释放速度的影响甚微. 因此,可以将这种新型智能药物缓释系统应用于肠道靶向给药.     

磁性微胶囊的制备及其药物缓控释性能

用乳液-凝胶法制备了磁性壳聚糖/海藻酸钠微胶囊. 在壳聚糖/海藻酸钠微胶囊中掺入Fe3O4磁性中空球, 使微胶囊具有磁靶向性能. 以头孢拉定作为模型药物研究了载药磁性微胶囊的载药量、包封率及药物缓控释性能等. 结果表明, 提高头孢拉定的初始浓度可以提高载药量, 却不利于提高药物的包封率. 所制备的微胶囊在各种缓冲溶液中长时间内具有显著的缓释效果, 并具有pH 刺激响应释放的性能, 即在模拟胃液中的药物释放率大大降低, 而在模拟体液和肠液中的释放时间大大延长, 可达50 h以上. 另外, 在外加磁场作用下, 微胶囊表现出良好的磁定向运动性能, 为磁靶向药物输送提供基础.     

Superparamagnetic pH‐sensitive multilayer hybrid hollow microspheres for targeted controlled release

The superparamagnetic multilayer hybrid hollow microspheres have been fabricated using the layer‐by‐layer assembly technique by the electrostatic interaction between the polyelectrolyte cation chitosan (CS) and the hybrid anion citrate modified ferroferric oxide nanoparticles (Fe₃O₄‐CA) onto the sacrificial polystyrene sulfonate microspheres templates after etching the templates by dialysis. The saturation magnetization and magnetite contents of the superparamagnetic multilayer hybrid hollow microspheres were 32.46 emu/g and 51.3%, respectively. The hybrid hollow microspheres showed pH‐sensitive characteristics. The adsorption and release of the basic dye (methylene blue) were applied to investigate the interaction between the amino groups of CS and the carboxyl groups of the Fe₃O₄‐CA nanoparticles in different pH media. The superparamagnetic pH‐sensitive multilayer hybrid hollow microspheres are expected to be used for the targeted controlled release of drugs or in diagnostics. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3135–3144, 2010