Liquid phase coating to produce controlled-release alginate microspheres

This study explored a liquid phase coating technique to produce polymethyl methacrylate (PMMA)-coated alginate microspheres. Alginate microspheres with a mean diameter of 85.6?µm were prepared using an emulsification method. The alginate microspheres, as cores, were then coated with different types of PMMA by a liquid phase coating technique. The release characteristics of these coated microspheres in simulated gastric (SGF) and intestinal (SIF) fluids and the influence of drug load on encapsulation efficiency were studied. The release of paracetamol, as a model hydrophilic drug, from the coated microspheres in SGF and SIF was greatly retarded. Release rates of Eudragit RS100-coated microspheres in SGF and SIF were similar as the rate-controlling polymer coat was insoluble in both media. Drug release from Eudragit S100-coated microspheres was more sustained in SGF than in SIF, due to the greater solubility of the coating polymer in media with pH greater than 7.0. The drug release rate was affected by the core:coat ratio. Drug release from the coated microspheres was best described by the Higuchi's square root model. The liquid phase coating technique developed offers an efficient method of coating small microspheres with markedly reduced drug loss and possible controlled drug release.     

Quantitative study of the production and properties of alginate/poly-L-lysine microcapsules

Alginate-polylysine-alginate (APA) microcapsules are of particular interest for their application as implants or for bioreactor cultures. Although their formation has been widely studied, there is still a lack of quantitative data describing resistance, membrance thickness and permeability. In this study, the quantitative application of a Texture Analyser for the measurement of capsule deformation yielded important results that permit comparison with other polymer systems used for encapsulation. Furthermore, single-membrane and multi-membrane capsules were formed in order to improve the modulation of the capsule properties. For single-membrane capsules, resistance was mostly affected by the incubation time in poly-L-lysine (PLL), the PLL molecular weight and concentration. The increase in resistance from 0.1 #45 0.01 g/capsules to 2 #45 0.2 g/capsules was linked to a membrane thickening (35-120 #181;m) and a decrease in permeability (150 to 40 kD). Thus, it was not possible to modify resistance and membrane permeability independently. Multi-membrane capsules with a resistance comparable to single-membrane capsules could be formed using various combinations of PLL molecular weights, and enabled uncoupling of permeability and resistance properties.     

Influence of viscosity and uronic acid composition of alginates on the properties of alginate films and microspheres produced by emulsification

This study investigated the influence of viscosity and uronic acid composition of alginates on the properties of alginate films and microspheres produced by emulsification. Tensile properties of films were determined while the yield, size, drug contents and release characteristics of the microspheres were examined. Tensile properties of calcium alginate matrix were significantly affected by the orientation and arrangement of the polymer chains. High viscosity alginates gave rise to higher yields and bigger microspheres. Generally, microspheres with high drug content and slower rate of drug release had high Ca²⁺ contents and were produced from alginates of higher viscosity. Within an alginate microsphere batch, small sized microsphere fractions had higher drug contents but showed faster drug release rates. Microspheres having a defined size range revealed great dependence of encapsulation efficiency and drug release rates on viscosity and extent of Ca²⁺-alginate interaction. Viscosity appeared to exert a predominant influence on the microsphere properties.     

Radiolabeling and evaluation of alginate blend-isoniazid microspheres by 99mTc for the treatment of tuberculosis in rabbit model

Isoniazid (INH) is the first line anti-tubercular drug that is widely used in the treatment of tuberculosis. ^99mTc-alginate-INH microsphere scintigraphy has been demonstrated to be a useful noninvasive imaging technique for microsphere deposits located in different organs of the rabbits. The aim of this study was to develop an improved formulation, to validate the formulation for long-time retention, as well as to assess radiotracer stability by novel quality control methods. Our study reports the labeling and evaluation of alginate blends-INH microspheres. The incorporation efficiency of optimized formulation was 89% w/w. The in vitro release study was carried out in simulated intestinal fluid at pH 7.4, and it was found that the formulation delivered the drug for 36 h. The labeling efficiency of ^99mTc-alginate blends-INH microspheres was seen at various pH (i.e. pH ranging from 5 to 7.5) and different concentration of stannous chloride dehydrate (i.e. 25–200 μg) and it was concluded that 96% labeling efficiency was achieved in case of pH 7.5 and 60 μg stannous chloride. The stability study was carried out in saline and serum and it was found that the complex was highly stable in vitro and in vivo. The blood clearance in rabbits showed bi-exponential pattern depicting that 50% of activity washed out at 2 h with t_1/2(Fast) was 2.1 h and t_1/2(Slow) was 12.5 h. Bio-distribution was normal and the experimental mice showed major accumulation of the radiolabeled formulation in liver, intestine, lungs and kidneys, indicating hepatobiliary and renal route of excretion. The distribution of the drugs to the lung was showing its efficiency in the treatment of tuberculosis.     

Bioefficacy of budesonide loaded crosslinked polyeletrolyte microparticles in rat model of induced colitis

A targeted delivery system for inflammatory bowel diseases, chitosan-Ca-alginate microparticles efficiently loaded with budesonide (BDS), were designed using one-step spray-drying process. They were eudragit-coated and examined for in vivo efficacy. Experimental colitis was induced by rectal instillation of 2,4,6-trinitrobenzene sulphonic acid (TNBS) into male Wistar rats. Drugs were administered by oral gavage daily for 5 days. Colon/body weight ratio, gross morphological and histological evaluation, and clinical activity score were determined as inflammatory indices. Individual clinical and histological evaluation showed that colitis severity was suppressed the most greatly in order BDS < BDS/C-Ca-A < E-BDS/C-Ca-A. Clinical activity score decreased in the same order. Statistical analyses of total score points indicate that the incorporation of BDS in microparticles had significant differences in favor of efficacy of designed delivery system with mucoadhesive and controlled release properties (one-way ANOVA, P?<?0.05). The results established the prediction by previous in vitro studies.     

Can alginate-based preloads increase weight loss beyond calorie restriction? A pilot study in obese individuals

This randomized, controlled, 2-week intervention study in 24 obese subjects tested the effect on body weight loss and gastrointestinal tolerance of consuming low viscous alginate fibre-based preloads of 3% concentration (500 ml volume) three times a day as an adjuvant to a calorie-restricted diet. The pilot study showed that intake of the alginate preloads was moderately acceptable to the majority of subjects but did not produce additional body weight loss beyond calorie restriction (−1.42 ± 0.38 kg) (n = 12) compared to control group (−1.56 ± 0.21 kg) (n = 8). These results do not support that alginate supplementation enhance the weight loss effects of a hypo-caloric diet, but a sufficiently powered long-term study is needed to explore whether alginate could be an aid for improving weight loss during caloric-restriction.     

壳聚糖／海藻酸钠-云南白药复合膜止血效果实验研究

目的观察壳聚糖/海藻酸钠—云南白药复合膜的止血性能。方法制备壳聚糖/海藻酸钠—云南白药复合膜组（Ⅰ组）同时设立模型对照组与明胶海绵对照组：壳聚糖/海藻酸钠复合止血膜组（Ⅱ组）,壳聚糖止血膜组（Ⅲ组）,明胶海绵组（Ⅳ组）进行比较。半定量评价改良壳聚糖止血膜的止血效果。结果 ：结果显示Ⅰ组与模型对照组及明胶海绵对照组的止血时间显著差异（P〈0.01）。结论壳聚糖/海藻酸钠—云南白药复合膜表现出显著的协同作用,止血作用显著强于其他各组,复合后膜的止血效果得到了较大提高,可望在创伤止血、外科手术上得到广泛应用     

Macrophage repolarization with targeted alginate nanoparticles containing IL-10 plasmid DNA for the treatment of experimental arthritis

In this study, we have shown for the first time the effectiveness of a non-viral gene transfection strategy to re-polarize macrophages from M1 to M2 functional sub-type for the treatment of rheumatoid arthritis (RA). An anti-inflammatory (IL-10) cytokine encoding plasmid DNA was successfully encapsulated into non-condensing alginate based nanoparticles and the surface of the nano-carriers was modified with tuftsin peptide to achieve active macrophage targeting. Enhanced localization of tuftsin-modified alginate nanoparticles was observed in the inflamed paws of arthritic rats upon intraperitoneal administration. Importantly, targeted nanoparticle treatment was successful in reprogramming macrophage phenotype balance as ∼66% of total synovial macrophages from arthritic rats treated with the IL-10 plasmid DNA loaded tuftsin/alginate nanoparticles were in the M2 state compared to ∼9% of macrophages in the M2 state from untreated arthritic rats. Treatment significantly reduced systemic and joint tissue pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) expression and prevented the progression of inflammation and joint damage as revealed by magnetic resonance imaging and histology. Treatment enabled animals to retain their mobility throughout the course of study, whereas untreated animals suffered from impaired mobility. Overall, this study demonstrates that targeted alginate nanoparticles loaded with IL-10 plasmid DNA can efficiently re-polarize macrophages from an M1 to an M2 state, offering a novel treatment paradigm for treatment of chronic inflammatory diseases.     

Pharmacokinetics,distribution, and excretion of sodium oligomannate,a recently approved anti-Alzheimer's disease drug in China

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease. In this study, an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices. The plasma pharmacokinetics, tissue distribution, and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were systematically investigated. Despite its complicated structural composition, the absorption, distribution, metabolism, and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate. Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration, with very low oral bioavailability in rats (0.6%–1.6%) and dogs (4.5%–9.3%). Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues. Sodium oligomannate could penetrate the blood-cerebrospinal fluid (CSF) barrier of rats, showing a constant area under the concentration-time curve ratio (CSF/plasma) of approximately 5%. The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability, supporting that excretion was predominantly renal, whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats. Moreover, only 33.7% (male) and 26.3% (female) of the oral dose were recovered in the rat excreta within 96 h following a single oral administration, suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.