Tailoring of alginate–gelatin microspheres properties for oral Ciprofloxacin-controlled release against Pseudomonas aeruginosa

Abstract

Context: Ciprofloxacin (Cip) is a broad spectrum antibiotic frequently used in the treatment of infectious diseases caused by Pseudomonas aeruginosa. Cip oral administration is commonly associated with poor drug biodisponibility, gastrointestinal tract irritation, and toxic undesirable side effects.

Objective: The aim of this work is to provide an oral biopolymeric system for controlled release of Cip.

Materials and methods: Alginate–gelatin blend microspheres were crosslinked in the presence of 1,2-propylene glycol, calcium, and glutaraldehyde. Studies of Cip encapsulation and release were performed. Matrix characteristics were studied simultaneously by optical microscopy and Fourier transform infrared spectroscopy (FTIR) using synchrotron light, and by texturometric analysis. Microsphere surface topologies were observed by scanning electron microscopy (SEM), atomic force microscopy (AFM), and epifluorescence microscopy.

Results: Microspheres crosslinked with glutaraldehyde showed about 80% Cip encapsulation and less than 10% Cip release under simulated gastric conditions in 15?min, while a controlled release profile was observed at intestinal environment conditions. Antimicrobial activity against P. aeruginosa showed an increasing bacterial growth inhibition in time. Finally, bovine serum albumin (BSA) was used as model protein for binding of macromolecules onto active surface of microspheres, with a consequently modulation of Cip release.

Discussion and conclusions: The results are indicating that alginate/gelatin matrix crosslinked via Ca²⁺ and glutaraldehyde can be tailored by decorating the microsphere surface with biological active molecules useful for targeting, making a potential tool to improve Cip oral administration for infection diseases.     

Matrix-Type Transdermal Patches of Verapamil Hydrochloride: In Vitro Permeation Studies Through Excised Rat Skin and Pharmacodynamic Evaluation in Rats

The objectives of this study were to develop matrix-type transdermal patches of verapamil hydrochloride (VRP) with pectin as a matrix polymer to investigate the influence of several terpenes on in vitro permeation of VRP through rat skin and to evaluate pharmacodynamic activity of transdermal formulations in rats. Matrix-type transdermal patches containing VRP were prepared using pectin as a matrix agent and propylene glycol as a plasticizer agent. Terpenes such as nerolidol, d-limonene, eucalpytol, menthone, and menthol were also used as a chemical enhancer to improve the skin penetration of VRP. The permeation studies were perfomed using Franz-type diffusion cells and full-thickness excised abdominal rat skin. Effects of terpenes on the permeation parameters of VRP were evaluated. In vitro skin permeation studies showed that nerolidol was the most promising enhancer among the enhancers examined in the present study, followed by d-limonene. Pharmacodynamic activity of the transdermal patches containing nerolidol or d-limonene was evaluated in rats by the measurement of systolic blood pressure for 360 min with the use of the tail cuff method. VRP transdermal patches significantly decreased the systolic blood pressure after 30 min and transdermal patches containing nerolidol and d-limonene maintained the decrease in blood pressure during the observation of 360 min.     

载胰岛素壳聚糖-果胶微球的制备及性能研究

目的以壳聚糖与果胶为载体,三聚磷酸钠、氯化钙为固化剂,制备载胰岛素的壳聚糖-果胶微球,并对微球的基本性质、载药性能及成型机制进行考察。方法采用离子移变胶凝法制备载胰岛素的壳聚糖-果胶微球,采用高效液相色谱法测定包封率,以微球形态、粒径、包封率作为考察指标,进行处方工艺的单因素筛选。用差示扫描量热法与傅里叶变换红外光谱法对微球的成型机制进行初步探讨。初步考察了载胰岛素壳聚糖-果胶微球的体外释药行为。结果胰岛素在0.8～60μg.mL-1内呈现良好的线性,相关系数r=0.999 8。所制备的微球形态圆整,平均粒径为（38.06±3.89）μm,包封率为（44.06±1.63）%。由DSC图谱推断,形成微球时,壳聚糖与果胶之间发生了相互作用。微球的FTIR图谱中未出现新的特征峰,推断在形成微球时,壳聚糖、果胶、胰岛素之间未发生化学反应。初步考察了载胰岛素壳聚糖-果胶微球体外释药呈现明显的缓释作用。结论本法制备工艺简单,重复性好,所制备的胰岛素微球外观圆整,粒径大小分布较均匀,具有明显缓释作用,但包封率不够理想,尚需进一步提高。     

酮洛芬果胶钙凝胶小球和海藻酸钙凝胶小球的制备及性能比较

目的酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球的制备及性能比较。方法利用果胶、海藻酸钠及二者不同比例,以酮洛芬为模型药物采用滴制法制备凝胶小球,考察2种多糖物质对药物包封率和释放行为的影响。利用大鼠肠囊外翻实验对凝胶小球的生物黏附性能进行比较,通过对释放机理的探讨和凝胶小球溶胀性的测定进一步证明2种凝胶小球释药行为的不同。结果酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球均具有良好的生物黏附性能,果胶钙凝胶小球主要通过溶胀作用缓慢释药,而海藻酸钙凝胶小球的释药与凝胶小球慢慢吸水后骨架溶蚀有关。结论酮洛芬果胶钙凝胶小球和酮洛芬海藻酸钙凝胶小球通过与生物黏膜的紧密结合缓慢释药,而二者的释放行为有所不同。     

果胶及果胶酶研究进展

果胶分子是由HGA、RG-Ⅰ和RG-Ⅱ3个结构区域构成，后二者为结构复杂的杂多糖成分，因此参与果胶分解的酶类也是复杂多样的，逐渐延伸了果胶酶概念的内涵．其应用已不再停留在最初的食品加工上，而是在纺织、造纸、化妆品等行业都有所发展，在天然产物提取以及果胶低聚糖的生理活性研究等方面也有了阶段性的进展，果胶酶的固定化研究也在逐步深入．     

汉麻果胶皂苷类成分分离及其抗真菌活性研究

目的获得汉麻果胶皂苷类成分的主要部位,进行抗真菌试验,测定其最小抑菌浓度值（M/C）。方法利用D101大孔树脂进行梯度洗脱,通过试管定性试验以及薄层色谱（TLC）法确定富集皂苷类成分洗脱部位,并采用微量液基稀释法研究其对4种常见致病真菌红色毛癣菌、须癣毛癣菌、犬小孢子菌和白色念珠菌的生物活性。结果80%浓度的洗脱物对红色毛癣菌、须毛癖菌、犬小孢子菌均具有抑制作用,其M/C值分别为16,8,2 ｜ig/mL。结论汉麻果胶皂苷类成分具有显著的抗真菌作用。     

稀有糖L-半乳糖及其衍生物的合成研究

目的 制备L-半乳糖及其中间体D-半乳糖醛酸、L-半乳糖酸-1,4-内酯,并优化工艺。方法 采用酶法水解果胶,制备D-半乳糖醛酸,并用正交试验设计法确立最佳酶水解工艺;D-半乳糖醛酸经还原、脱水转化为L-半乳糖酸-1,4-内酯,进一步还原合成L-半乳糖。结果 酶水解最佳条件为50℃反应2 h,酶-果胶比为1.5：10。合成产物结构经¹H-NMR、¹³C-NMR表征。合成产率为31.4%。结论 方法操作简便,步骤短,反应收率高,具有工业化生产前景。     

Fabrication and Characterization of Chitosan and Pectin Nanostructured Multilayers

Chitosan has been used for drug delivery applications for many years, and pectin has been recently used for several biomedical applications too. Both chitosan and pectin have shown to possess mucoadhesive properties. We report the assembly and characterization of biocompatible and biodegradable multilayers based on the layer‐by‐layer (LbL) deposition of chitosan and pectin. The dependence of the multilayer properties on the degree of esterification of pectin, as well as on the assembly pH, is characterized, and the mucoadhesiveness of the multilayers is estimated at oral and gastric pHs. The LbL assembly of chitosan and pectin for the fabrication of hollow capsules is carried out for the first time, and its potential use for drug delivery applications opens new prospects for the production of novel drug delivery materials.

     

In Vitro Evaluation of Calcium Pectinate: A Potential Colon-Specific Drug Delivery Carrier

Calcium pectinate (CaP)—the insoluble salt of pectin—can potentially be used as a colon-specific drug delivery system. The use of CaP as a carrier was based on the assumption that, like pectin, it can be decomposed by specific pectinolytic enzymes in the colon but that it retains its integrity in the physiological environment of the small bowel. The biodegradation of the carrier was characterized by monitoring the percent cumulative release of the insoluble drug indomethacin, incorporated into pectin or CaP matrices. Compressed tablets of pectin and indomethacin were analyzed for degradation in the presence of Pectinex 3XL, a typical pectinolytic enzyme mixture, and in the presence of the human colonic bacterium Bacteroides ovatus. The degradation of CaP-indomethacin tablets was assessed in the presence of Pectinex 3XL and in rat cecal contents. The release of indomethacin was significantly increased (end-time percentage cumulative release vs control) in the presence of Pectinex 3XL (89 ± 20 vs 16 ± 2 for CaP tablets), Bacteroides ovatus (12 and 22 vs 5.2 for pectin tablets), and rat cecal contents (61 ± 16 vs 4.9 ± 1.1 for CaP tablets). The weight loss of tablet mass was significantly higher (end-time dry weight vs control) in the presence of Pectinex 3XL (0 vs 75 ± 6% of initial weight for CaP tablets). These findings indicate the potential of CaP, compressed into tablets with insoluble drug, to serve as a specific drug delivery system to the colon.     

膳食纤维不同成分对大鼠脂质代谢的影响

本文观察了3种不同膳食纤维(DF)制成品(纤维素、果胶、琼脂)对高胆固醇膳大鼠脂质代谢的影响。结果发现:果胶和纤维素组自实验2周末,琼脂组于6周末与对照组相比有明显的降低血清TC作用;3种DF均有不同程度降低肝胆固醇作用;各组血清TG、HDL-C,HDL_2-C,HDL_3-C间无显著差异;纤维素组和果胶组HDL-C/TC比值明显高于对照组。3种DF均可使大鼠排粪量增加,对大鼠摄食量及生长无影响。