Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH-sensitive drug release property

Composite microparticle drug delivery systems based on chitosan, alginate and pectin with improved pH sensitivity were developed for oral delivery of protein drugs, using bovine serum albumin (BSA) as a model drug. The composite drug-loaded microparticles with a mean particle size less than 200 μm were prepared by a convenient shredding method. Since the microparticles were formed by tripolyphosphate cross-linking, electrostatic complexation by alginate and/or pectin, as well as ionotropic gelation with calcium ions, the microparticles exhibited an improved pH-sensitive drug release property. The in vitro drug release behaviors of the microparticles were studied in simulated gastric (pH 1.2 and pH 5.0), intestinal (pH 7.4) and colonic (pH 6.0 and pH 6.8 with enzyme) media. For the composite microparticles with suitable compositions, the releases of BSA at pH 1.2 and pH 5.0 could be effectively sustained, while the releases at pH 7.4, pH 6.8 and pH 6.0 increased significantly, especially in the presence of pectinase. These results clearly suggested that the microparticles had potential for site-specific protein drug delivery through oral administration.     

Studies in the development of nateglinide loaded calcium alginate and chitosan coated calcium alginate beads

Nateglinide loaded alginate-chitosan beads were prepared by ionic gelation method for controlling the drug release by using various combinations of chitosan and Ca2+ as cation and alginate as anion. IR spectrometry, scanning electron microscopy, differential scanning calorimetry and X-ray powder diffractometry were used to investigate the physicochemical characteristics of the drug in the bead formulations. The calcium content in beads was determined by atomic absorption spectroscopy. The swelling ability of the beads in different media (pH 1.2, 4.5, 6.8) has been found to be dependent on the presence of polyelectrolyte complex of the beads and the pH of the media. The ability to release the Nateglinide was examined as a function of chitosan and calcium chloride content in the gelation medium. It is evident that the rate of drug release and its kinetics could be controlled by changing the chitosan and the calcium chloride concentrations. Calcium alginate beads released more than 95% of drug with in 8 h; whereas coated beads sustained the drug release and released only 75-80% of drug. The drug release mechanism analyzed indicates that the release follows either "anomalous transport" or "case-II transport".     

Characteristics and antioxidant activity of catechin-loaded calcium pectinate gel beads prepared by internal gelation

Catechin-loaded calcium pectinate gel beads prepared by internal gelation were characterized for their catechin entrapment efficiency and release behavior. The entrapment efficiency was higher when the beads were prepared with a lower catechin-to-pectin ratio, shorter gelling time, higher pectin concentration, and lower acetic acid concentration. The entrapment efficiency was much higher under all tested conditions, when the beads were prepared by internal gelation instead of external gelation. The catechin release was slower for the beads prepared with lower catechin-to-pectin ratio, longer gelling time, and higher concentrations of pectin and acetic acid in both simulated gastric and intestinal fluids. Antioxidant power of catechin was effectively maintained in alkaline simulated intestinal fluid when catechin was entrapped within the beads, compared to cases where it was not entrapped, indicating that the beads can protect catechin molecules from the alkaline environment and release them in a sustained fashion.     

Preparation and properties of novel hydrogels from oxidized konjac glucomannan cross-linked chitosan for in vitro drug delivery

In this paper, a novel composite hydrogel was prepared by the use of dialdehyde konjac glucomannan (DAK) as macromolecular cross-linking agent for chitosan (CS). This biocompatible material cross-links and gels in minutes. The structure and morphology were characterized by various analyses. The results indicate that the hydrogels formed through the Schiff-base reaction between the amino groups of CS chains and the aldehyde groups of DAK. The cross-link density (rho(x)) increases with the enhancement of DAK content in hydrogels, while equilibrium swelling ratio (SR) and the average molecular weight between cross-links (Mc) value decrease. Drug release was evaluated by varying the pH of the release medium, reversed dependence of release rate on the equilibrium SR of hydrogel indicated that drug release may be impeded by the association of drug with the polymer. Importantly, this process offers an entirely new window of materials preparation when compared with the traditional preparation of CS-based hydrogels with small molecules cross-linking agent.     

Gelation of aqueous pectin solutions: a dynamic light scattering study

We report the dynamic light scattering study of the gelation of aqueous solutions of the biopolymer, pectin, induced by the addition of calcium chloride. The time correlation function data are analyzed under the framework of the coupling model. As the solution enters the semidilute regime where gelation sets in, the relaxation process shows a stretched exponential behavior. The stretching exponent decreases and the characteristic time of the stretched exponential diverges as the system evolves to a gel. Aqueous pectin solutions in the presence of 0.1 M NaCl show similar behavior. Thus, the molecular relaxation modes of pectin solutions can be well described by the coupling model.     

离子凝聚法制备负载流感疫苗的壳聚糖微球

采用三聚磷酸钠(TPP)作为离子交联剂, 应用离子凝聚法制备负载流感疫苗的壳聚糖微球. 筛选出壳聚糖起始质量分数为1%. TPP的浓度对壳聚糖微球的制备影响较大, 采用低浓度的TPP(200 μg/mL)制备的微球放置过夜均出现沉淀现象, 高浓度的TPP(800 μg/mL)在制备过程中出现絮状沉淀. 固化比影响微球的释放行为, 固化比为1∶1的微球爆炸式释放率达到90％, 固化比为1∶3的微球6 h后逐步释放, 12 h后释放率达到95％. 固化比为1∶5的微球6 h后没有明显的释放行为. 壳聚糖溶液的pH对微球的制备和释放没有显著的影响. 通过对负载流感疫苗的壳聚糖微球的制备条件和释放行为的研究结果表明, pH=5.6的壳聚糖溶液, 固化比为1∶3, TPP的质量浓度为400 μg/mL是较理想的流感疫苗壳聚糖微球的制备条件.     

Preparation, characterization of hydrophilic and hydrophobic drug in combine loaded chitosan/cyclodextrin nanoparticles and in vitro release study

The compound nanoparticles of chitosan (CS) and cyclodextrin (CD) loading with hydrophilic and hydrophobic drug simultaneously were prepared via the cross-linking method. Methotrexate (MTX) and calcium folinate (CaF) were selected as the model drugs. The prepared nanoparticles were characterized by FT-IR spectroscopy to confirm the cross-linking reaction between CS and cross-linking agent. X-ray diffraction (XRD) was performed to reveal the form of the drug after encapsulation. The average size of nanoparticles ranged from 308.4 ± 15.22 to 369.3 ± 30.01 nm. The nanoparticles formed were spherical in shape with high zeta potentials (higher than +30mV). In vitro release studies in phosphate buffer saline (pH 7.4) showed an initial burst effect and followed by a slow drug release. Cumulative release data were fitted to an empirical equation to compute diffusional exponent (n), which indicated the non-Fickian trend for drug release.     

Relationship between physicochemical characteristics and functional properties of chitosan

In order to select an ideal chitosan (CS) species as a material for implantation vehicle to control drug release in the body, the relationship between physicochemical characteristics (including molecular weight, degree of deacetylation, and viscosity) and functional properties (including ability to form spherical gel, control of drug release from CS gel, and biodegradation of CS) was investigated for various CS. The ease of spherical gel formation in aqueous amino acid solution or aqueous solution containing metal ions was affected mainly by viscosity of the CS solution. Drug diffusion rate from the CS gel was controlled by density of the gel matrix structure, which was governed by viscosity of the CS solution prior to gelation. Biodegradation of CS tended to vary with degree of deacetylation. However, linear relationships for these trends were not observed, and the possibility that characteristics other than CS molecular weight, degree of deacetylation, and viscosity of the CS solution, such as distribution of acetamide groups in the CS molecule affect functional properties of CS, was also indicated. These observations demonstrate that CS functions are affected by various CS characteristics and that investigation of individual CS characteristics is important for the selection of the appropriate CS as a material for drug delivery vehicles.     

Controlled Release of Sulfasalazine Release from “Smart” Pectin Gel Microspheres under Physiological Simulated Fluids

Sulfasalazine (SLZ) is a synthetic nonsteroidal anti-inflammatory drug used mainly for the treatment of an inflammatory bowel and other diseases. Two pectins with different methylation degrees were blended to synthesized gel microspheres by ionotropic gelation for SLZ encapsulation. The encapsulation efficiency was found to be around of 99% in all formulations tested. However, different SLZ release profiles related to the methylation degrees of pectin were observed. Mixture of low methylated (LM) and high methylated (HM) pectins in the presence of calcium(II) displayed the best microsphere morphologies among the formulations tested determined by optical and electronic microscopies. The percentage of drug release using a mixture of LM and HM pectins after 255?min in simulated gastric fluid (pH?=?1.2), simulated intestinal fluid (pH?=?6.8), and phosphate buffer (pH?=?7.4) were 15.0%, 47.0%, and 52.2%, respectively.     

低温辐射聚合制备聚合物药的慢释放研究

本文研究了低温辐射慢释放药的单体配比、药物含量及辐射刺量对药物释放速率的影响。结果表明,增加疏水性单体MMA,可以有效地控制大分子量药物消炎痛的释放速率;增加MMA及EDGMA,可以有效地控制小分子量药物5-Fu的释放速率;增加5-Fu的比例,可以降低5-Fu的释放速率;随辐照剂量的增加,聚合物药中5-Fu的释放量降低,二者之间成正比关系。     

Characterization and in vitro release kinetics of chitosan based biocomposites from Scotch Bonnets

The main aim of this study is to formulate the combination of the bioactive composite containing chitosan/β -tricalcium phosphate (CH/β-TCP) as potential drug delivery platforms for the sustained release of antibiotics. Herein the mode of amoxicillin (AMX) maintained in the β-TCP/chitosan composite was characterized using XRD, FT-IR to confirm the phase purity and functional groups. SEM was used to examine the size and shape of particles. The SEM images of the biocomposites after drug release confirmed that they are biodegradable. In vitro drug release experiments in PBS (pH 7.4) revealed a sustained release profile in a neutral medium. Drug release profiles were evaluated according to five different kinetic models including Zero Order, First Order, Higuchi, Hixon Crowel, and Korsmeyer-Peppas. The release profile was best expressed by the Korsmeyer Peppas model because the results showed high linearity. Overall, the positive effect of chitosan coating on the drug elution profile of β-TCP as carriers for the controlled delivery of antibiotics was regarded as biocompatible for the controlled drug delivery system.     

聚乳酸/壳聚糖纳米纤维结构形成的影响条件及其生物矿化活性

以二氧六环/冰醋酸为溶剂体系,采用相分离法制备了聚乳酸(PLA)/壳聚糖(CS)复合纳米纤维结构的组织工程支架,探讨了不同CS含量、不同凝胶温度及不同分子量对PLA/CS复合支架纳米纤维结构的影响以及支架的生物活性。结果表明,凝胶温度对PLA/CS复合材料的纳米纤维结构影响较大,且随着温度的降低,结构的微观尺寸也逐渐增大,从纳米级上升到普通的尺寸结构;CS含量对PLA/CS复合支架的基体结构影响不大;实验范围内PLA分子量对PLA/CS复合支架的纳米纤维结构有重要影响:分子量大的样品,较易得到PLA/CS复合纳米纤维结构的材料,而分子量小的样品则不能得到纳米纤维结构。另外,生物矿化实验表明CS的添加有利于PLA/CS复合材料生物活性的提高。     

Chitosan‐Based Thermo/pH Double Sensitive Hydrogel for Controlled Drug Delivery

A series of thermo/pH sensitive N‐succinyl hydroxybutyl chitosan (NSHBC) hydrogels with different substitution degrees of succinyl are prepared for drug delivery. Rheology analysis shows that the gelation temperature of NSHBC hydrogels is 3.8 °C higher than that of hydroxybutyl chitosan (HBC) hydrogels. A model drug bovine serum albumin (BSA) is successfully loaded and released. NSHBC hydrogels show excellent pH sensitivity drug release behaviors. After incubation for 24 h, 93.7% of BSA is released from NSHBC hydrogels in phosphate buffer saline (PBS) (pH 7.4), which is significantly greater than that of 24.6% at pH 3.0. In contrast, the release rate of BSA from HBC is about 70.0% at pH 3.0 and 7.4. Thus, these novel hydrogels have the prominent merits of high adaptability to soluble drugs and pH sensitivity triggered release, indicating that NSHBC hydrogels have promising applications in oral drug delivery.     

空心纳米磷酸钙载药体系的制备与表征

非离子表面活性剂Tween 80和PEG 6000在水溶液中以一定的比例混合可形成稳定的类磷脂囊泡结构,这些囊泡可以作为模板来合成磷酸钙纳米空球颗粒。所制备的磷酸钙材料的结构和形貌通过TEM,SEM,FTIR,XRD进行了表征,是尺寸为100～150 nm左右的无定形磷酸钙空心颗粒。磷酸钙具有良好的生物相容性,因此这些具有空心结构特征的磷酸钙可发展为理想的载药体系。我们以牛血清蛋白(BSA)为模型体系研究了材料的载药和释放性能,发现所获得的空心纳米磷酸钙不仅具有良好的蛋白质负载量而且还具有优异的可释放性,明显优于传统的羟基磷灰石体系。     

Preparation, characterization and in vitro release study of carvacrol-loaded chitosan nanoparticles

The fabrication of carvacrol-loaded chitosan nanoparticles was achieved by a two-step method, i.e., oil-in-water emulsion and ionic gelation of chitosan with pentasodium tripolyphosphate. The obtained particles possessed encapsulation efficiency (EE) and loading capacity (LC) in the ranges of 14-31% and 3-21%, respectively, when the initial carvacrol content was 0.25-1.25 g/g of chitosan. The individual particles exhibited a spherical shape with an average diameter of 40-80 nm, and a positively charged surface with a zeta potential value of 25-29 mV. The increment of initial carvacrol content caused a reduction of surface charge. Carvacrol-loaded chitosan nanoparticles showed antimicrobial activity against Staphylococcus aureus, Bacillus cereus and Escherichia coli with an MIC of 0.257 mg/mL. The release of carvacrol from chitosan nanoparticles reached plateau level on day 30, with release amounts of 53% in acetate buffer solution with pH of 3, and 23% and 33% in phosphate buffer solutions with pH of 7 and 11, respectively. The release mechanism followed a Fickian behavior. The release rate was superior in an acidic medium to either alkaline or neutral media, respectively.     

Preparation of poly(N-isopropylacrylamide) emulsion gels and their drug release behaviors

Stimuli-sensitive drug delivery systems (DDSs) have attracted considerable attention in medical and pharmaceutical fields; thermosensitive DDS dealing with poly(N-isopropylacrylamide) (poly(NIPA)) have been widely studied. Novel NIPA emulsion gels, i.e., NIPA hydrogels containing distributed oil (oleyl alcohol) microdroplets, were synthesized by means of an emulsion-gelation method in which the polymerization of hydrogels in an aqueous phase in an oil-in-water (O/W) emulsion and the loading of a lipophilic drug (indomethacin) dissolved in an oil phase were accomplished simultaneously. The pulsatile (on-off) drug release from the NIPA emulsion gel loading indomethacin to a phosphate buffered saline (PBS) solution was successfully controlled by a temperature swing between 25 degrees C (release off) and 40 degrees C (release on). The mechanism of the pulsatile drug release was discussed in relation to the diffusion rate, distribution ratio, solvent exchange of NIPA hydrogels, and drug release from an NIPA organogel. The mechanism was as follows: the solvent exchange occurred within the NIPA emulsion gel (the NIPA gel-network absorbed oleyl alcohol with indomethacin) at temperatures above the LCST, and the diffusion rate of indomethacin through the solvent-exchanged gel was higher at 40 degrees C than at 25 degrees C.     

Studies of Ciprofloxacin Encapsulation on Alginate/Pectin Matrixes and Its Relationship with Biodisponibility

Screening of ciprofloxacin (Cip) with selected biopolymers brings about 90% antibiotic interactions with a coacervate composed of alginate/high metoxylated pectin in 2:1 ratio. Fourier transform infrared spectroscopy analysis provides information about the nature of this interaction, revealing ionic and hydrophobic patterns among the molecules. Alginate/high methoxylated pectin gel microspheres developed by ionic gelation encapsulates 46.8?±?5.0% Cip. The gel matrix can release Cip in a sustained manner, releasing 42.7?±?0.2% in 2?h under simulated stomach pH conditions, and 83.3?±?1.1% Cip release in 80?mM phosphate at pH?=?7.40 (intestinal). The increase of sodium chloride from 50 to 200?mM implies a Cip release from 69.0?±?1.5% to 95.1?±?3.6% respectively in 2?h. Scanning electron microscopy revealed the cohesive effect of HM pectin over alginate molecules on the microsphere surface. Those results guarantee all Cip contained in the alginate/HM pectin microspheres could be released in an established kinetic profile along the gastrointestinal tract, avoiding the Cip undesirable side effects during absorption.     

香草醛交联壳聚糖载药微球的性能及其成球机理分析

以壳聚糖溶液为水相、液体石蜡为油相形成油包水型乳液, 以香草醛为交联剂, 采用乳化交联法制得壳聚糖微球. 结合IR光谱和XRD测试, 分析了壳聚糖交联固化成球的机理: 壳聚糖和香草醛之间所发生的Schiff碱反应和氢键的形成以及缩醛化反应, 以此为基础共同形成交联结构从而使壳聚糖交联固化成球. 探讨了交联后壳聚糖微球结晶度降低的原因: 壳聚糖固化时分子链未充分进行有序的结晶排列, 交联后的壳聚糖结构较复杂, 从而破坏了原壳聚糖分子的规整性. 选用盐酸小檗碱为模型药物, 制备了香草醛交联的壳聚糖载药微球, SEM结果显示, 载药微球表面致密且球形度好, 微球粒径在5-15 μm之间. 此外, 采用分光光度计对载药微球的载药率、药物包封率和药物体外释放性质进行了测试和分析, 结果表明载药微球缓释效果明显.     

海藻酸盐凝胶化及其在软骨组织工程和药物控释领域的应用（专题报道）

 介绍了海藻酸盐水溶液的凝胶化及其临界行为和松弛临界指数n.提出了将凝胶化按高分子的分子链长短分为生长型和交联型两类,前者为无规交联,符合逾渗连接的条件;后者大分子链间交联,不符合无规逾渗连接的条件.介绍了微囊化细胞载体、预成型支架和可注射支架,能够为软骨细胞提供良好的三维生长环境;通过LbL、二价离子交联等自组装技术,海藻酸能够实现对多种类型药物的包埋和控释.     

Gelation behavior of thermoplastic-modified epoxy systems during polymerization-induced phase separation

The rheological behavior and gelation characteristics of epoxy blends are of critical importance to property study and industrial application. In this work, we studied the rheological behavior and structural transition of different thermoplastics, including polyetherimide, polymethylmethacrylate, and polyethersulfone (PES), modified epoxy systems by using rheometry instrument, differential scanning calorimetry, time-resolved light scattering, and scanning electronic microscopes. At the same molecular weight level of thermoplastics, different epoxy blends show profound diversities on the rheological and gelation behavior due to the large differences in phase separation and curing process. For early phase-separation systems of PES-modified epoxy blends, two gel points are identified, which correspond to physical gelation and chemical gelation, respectively. With the variation of the PES molecular weight and curing rate, dramatic changes in gel time and critical exponent were observed. As the molecular weight of thermoplastics is increased, the gelation time becomes shorter and the gel strength gets lower, while the faster curing rate would increase the physical gel strength significantly.