Formulation and evaluation of ketorolac tromethamine-loaded albumin microspheres for potential intramuscular administration

The objective of this work was to prepare and evaluate ketorolac tromethamine-loaded albumin microspheres using a factorial design. Albumin microspheres were prepared by emulsion cross-linking method. Selected formulations were characterized for their entrapment efficiency, particle size, surface morphology, and release behavior. Analysis of variance (ANOVA) for entrapment efficiency indicated that entrapment efficiency is best fitted to a response surface linear model. From the statistical analysis it was observed that as the drug:polymer (D∶P) ratio and volume of glutaraldehyde increased, there was a significant increase in the encapsulation efficiency. Scanning electron microscopy of the microspheres revealed a spherical, nonporous and uniform appearance, with a smooth surface. Based on the entrapment efficiency and physical appearance, 9 formulations were selected for release study. The maximum particle size observed was below 40 μm. The release pattern was biphasic, characterized by an initial burst effect followed by a slow release. All selected microspheres, except those having less polymer proportion (D∶P ratio is 1∶1), exhibited a prolonged release for almost 24 hours. On comparingr ² values for Higuchi and Peppas kinetic models, different batches of microspheres showed Fickian, non-Fickian, and diffusion kinetics. The release mechanism was regulated by D∶P ratio and amount of cross-linking agent. From the experimental data obtained with respect to particle size and extent of drug relaase, it could be concluded that the prepared microspheres are useful for once-a-day intramuscular administration of ketorolac tromethamine. Published: February 23, 2007     

高分子药物缓释用壳聚糖微球的制备

本文采用了先交联制备可溶胀的壳聚糖载体微球,后将模型高分子药物以被动吸咐方式担载在溶胀的微球内的两步法,制备缓释高分子药物微球,避免了高分子药物接触有机试剂引起的活性损失。     

Preparation of biodegradable microspheres and matrix devices containing naltrexone

In this study, the use of biodegradable polymers for microencapsulation of naltrexone using solvent evaporation technique is investigated. The use of naltrexone microspheres for the preparation of matrix devices is also studied. For this purpose, poly(L-lactide) (PLA) microspheres containing naltrexone prepared by solvent evaporation technique were compressed at temperatures above the Tg of the polymer. The effect of different process parameters, such as drug/polymer ratio and stirring rate during preparation of microspheres, on the morphology, size distribution, and in vitro drug release of microspheres was studied. As expected, stirring rate influenced particle size distribution of microspheres and hence drug release profiles. By increasing the stirring speed from 400 to 1200 rpm, the mean diameter of microspheres decreased from 251 μm to 104 μm. The drug release rate from smaller microspheres was faster than from larger microspheres. However, drug release from microspheres with low drug content (20% wt/wt) was not affected by the particle size of microspheres. Increasing the drug content of microspheres from 20% to 50% wt/wt led to significantly faster drug release from microspheres. It was also shown that drug release from matrix devices prepared by compression of naltrexone microspheres is much slower than that of microspheres. No burst release was observed with matrix devices. Applying higher compression force, when compressing microspheres to produce tablets, resulted in lower drug release from matrix devices. The results suggest that by regulating different variables, desired release profiles of naltrexone can be achieved using a PLA microparticulate system or matrix devices.     

施氮深度和水分胁迫对藜麦幼苗生理及产量的影响

为了探讨藜麦应对施肥深度和水分胁迫的响应,该文以藜麦(Chenopodium quinoa)为材料,在盆栽条件下,设置3种施氮处理[D1(控释尿素施在0～8 cm深度)、D2(控释尿素施在8～16 cm深度)、D3(控释尿素施在16～24 cm深度)]和3种水分处理[W1(正常供水)、W2(中度干旱)、W3(重度干旱)],分析施氮深度和水分胁迫对藜麦幼苗生理及产量的影响。结果表明：(1)相同水分条件下,随着施肥深度的增加,藜麦生长指标(株高、茎粗、叶面积、地上部生物量、主根长、根系表面积、根系体积)、生理指标[超氧化物歧化酶(SOD)活性、过氧化物酶(POD)活性、过氧化氢酶(CAT)活性、可溶性糖含量、可溶性蛋白含量、叶绿素总量]和产量指标呈先升高后降低趋势。D2处理(适当的深施氮肥)均高于D1处理(浅层施氮)和D3处理(底层施氮)。(2)相同施氮深度条件下,随着干旱胁迫程度的增加,藜麦生长指标和产量指标呈逐渐降低的趋势,生理指标均呈先升高后降低的趋势。说明藜麦幼苗对水分需求明显,可通过增加抗氧化酶活性和渗透调节物质适应一定程度的干旱,生产实践中应注意苗期水分的供应,以促进生育后期产...     

左旋多巴甲酯缓释微球的研究

目的：由于长期服用左旋多巴治疗帕金森病,其药物浓度波动刺激易引起异动症,本实验旨在制备突释小,药物释放浓度稳定的左旋多巴甲酯微球制剂。方法：将左旋多巴甲酯用复乳法包裹于PLGA微球内,采用C18反相色谱研究药物包封率和体外释放行为。结果：通过调节药物浓度和不同高分子组合筛选出突释小,包封率高且缓慢释放的处方。结论：左旋多巴甲酯包裹于PLGA能实现理想的缓释效果,降低药物浓度波动,为后期药效学实验提供基础。     

淹水条件下控释氮肥对污染红壤中重金属有效性的影响

采用淹水培养方法研究了不同氮水平(100、200和400 mg/kg,分别记为1、2、3)下普通尿素(PU)、硫包膜尿素(SCU)、树脂包膜尿素(PCU)和硫加树脂双层包膜尿素(SPCU)对污染红壤中Cd、Pb、Cu、Zn有效性的影响.结果表明,不同包膜尿素对土壤pH值和水溶性SO42-含量有较大影响.各施氮处理红壤pH值随着施氮量的增加(除5d时PU和60 d时SCU)而增加,不同包膜尿素对土壤中水溶性SO42-含量有较大影响,在同一施氮水平下不同包膜尿素处理间土壤pH值和土壤中水溶性SO42-含量差异较大.60 d培养期间PU、SCU、PCU和SPCU处理pH值比对照分别升高0.17-0.38、0.08-0.27、0.07-0.36和0.10-0.21;水溶性SO42-含量PU、SCU和PCU处理比对照分别升高39.5％-157.3％、40.9％-94.5％和7.55％-55.8％,而SPCU处理降低5.67％-90.7％.不同尿素类型和氮肥的施用量对红壤Cd、Pb、Cu和Zn有效性的影响均存在显著差异.60 d培养期间红壤有效态Cd含量以树脂包膜尿素100 mg N/kg下最低,其有效态Cd含量比对照显著降低20.7％-69.8％;有效态Pb、Cu和Zn含量以普通尿素400 mg N/kg下最低,其有效态Pb、Cu和Zn含量比对照分别显著降低17.0％-54.2％、18.5％-34.6％和15.6％-59.5％.随施氮量提高,PU处理有效态Cd含量先升高后降低,有效态Pb、Cu和Zn含量逐渐降低;SCU处理有效态Pb含量逐渐降低,有效态Cd、Cu和Zn含量变化规律不一致;PCU处理有效态Cd含量逐渐升高,有效态Pb、Cu和Zn含量变化规律不一致;SPCU处理有效态Cd、Pb、Cu和Zn含量逐渐降低.有效态Pb和Zn含量与pH值和水溶性SO42-含量呈显著负相关,有效态Cd与水溶性SO42-含量呈显著正相关.在多重金属污染红壤中,可考虑不同控释氮肥的配合使用,降低土壤中重金属的有效性.     

固定化微球降解土壤中PAEs效果及影响因素

旨为研究土壤邻苯二甲酸酯污染修复中,固定化微球降解土壤中邻苯二甲酸酯的效果及影响因素。以海藻酸钠为载体,采用包埋法对课题组前期提取的微小杆菌进行固定化,比较固定化微球和游离菌降解土壤中邻苯二甲酸酯(Phthalates esters,PAEs)的效果及pH、温度、重金属、无机盐等对降解菌降解目标物的影响。结果显示:(1)在土壤环境相同条件下,固定化微球对邻苯二甲酸二甲酯(Dimethyl ortho-phthalate,DMP)、邻苯二甲酸二正丁酯(Di-n-butyl ortho-phthalate,DnBP)和邻苯二甲酸二(2-乙基己)酯(Bis(2-ethylhexyl)ortho-phthalate,DEHP)的降解效果高于游离菌,DMP在7 d可降解完全,DnBP在10 d内可降解完全,DEHP在20 d降解率63.73%;而游离菌则在15 d内完全降解DMP,20 d内完全降解DnBP,DEHP在20 d降解率48.77%;(2)不同pH值时,固定化微球对DMP、DnBP、DEHP的降解率均高于游离菌,pH9时,固定化微球对于DMP、DnBP、DEHP的降解率最高分别为96.81%、89.39%、58.35%;(3)不同温度,固定化微球对DMP、DnBP、DEHP的降解率也均高于游离菌,温度为30℃时,固定化微球对于DMP、DnBP、DEHP的降解效率达到最高,分别为96.27%、89.19%、59.01%;(4)重金属使游离菌对DMP、DnBP、DEHP降解率下降较多,而使固定化微球对DMP、DnBP的降解率仅下降了16.35%、9.95%,DEHP不仅没有降低,反而增加2.49%,说明重金属对游离菌起到很强的抑制作用,但对于固定化微球的降解效果影响较小;(5)盐碱条件下,中性盐极大降低了游离菌和固定化微球降解DMP、DnBP、DEHP的降解能力,碱性盐和混合盐对降解菌影响较小,且增强了固定化微球对DnBP、DEHP的降解能力。固定化微球降解PAEs效果明显高于游离菌,对外界环境有更好的适应能力,且对重金属、无机盐污染环境有一定的抵御能力。     

丝素微球的制备方法研究进展

丝素蛋白因其特殊的物理化学性质,为制备不同形态的材料提供了依据;丝素蛋白也因其良好的生物相容性、生物降解性为生物材料应用提供了重要的临床选择。本文综述了国内外学者对丝素微球的制备方法的探究,包括乳化法、喷雾干燥法、层流射流技术以及自组装方法,并比较了各种制备方法的优缺点。此外,本文还介绍了丝素微球在药物缓释领域中的应用进展,并提出了几个针对制备丝素微球亟需解决的问题。     

Characteristics of microspheres formed in PCR with bacterial genomic DNA or plasmid DNA as templates

Earlier, we discovered that, along with linear DNA fragments, nano- and microparticles of DNA and their aggregates are formed in the PCR with yeast genomic DNA used as a template and gene-specific or partially complementary primers. The size of the microparticles (microspheres) varied in the range of 0.5 to 3–4 μm. Only thermostable KlenTaq polymerase but not Taq polymerase could effectively generate microspheres. In this work, we demonstrate that KlenTaq polymerase can produce microspheres of variable size (1 to 7 μm in diameter) if genomic DNA of the bacterium Acidithiobacillus ferrooxidans and partially complementary primers are present in the PCR mixture. Conditions for generation of DNA microparticles in PCR with Taq-polymerase and bacterial genomic DNA as template were also elaborated. It was also found that mainly large microspheres of up to 7 μm accumulated in PCR with plasmid DNAs used as templates and gene-specific primers in the presence of KlenTaq polymerase or mixtures of KlenTaq and Pfu polymerases. Besides, small aggregates, as well as linear branched structures and three-dimensional conglomerates of fused microspheres, were also revealed in the PCR mixtures. UV absorption spectra of native DNA microspheres and microspheres that had undergone heating at 93°C were registered. The key role of Mg²⁺ cations in the formation and stabilization of the microsphere structure was established.     

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting

An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500–2000 rpm) and emulsifier concentrations (0.75%–1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat: core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU. Published: February 16, 2007