Optimization of Preparation of Oregano Oil Microspheres by Box-Behnken Response Surface Methodology

[Objectives]To optimize the formulation and preparation of oregano oil microspheres by Box-Behnken response surface methodology.[Methods]Chitosan was used as the carrier material to prepare oregano oil microspheres by emulsion crosslinking method.The encapsulation efficiency,drug loading and ID 50 were used as the evaluation indicators,and the comprehensive score(OD)obtained by"coefficient of variation-AHP comprehensive weighting method"was used as the final evaluation indicator.The formulation design and preparation process were optimized by single factor experiment and Box-Behnken response surface methodology,and the optimal process parameters were determined.[Results]The optimal formulation and preparation process parameters of oregano oil microspheres were as follows:the ratio of oregano oil to chitosan was 2∶1,the emulsifying speed of double emulsion was 200 r/min,the amount of emulsifier in the colostrum was 4%,and the volume of curing agent was 1.0 mL.The average encapsulation efficiency was 45.33%±1.32%,the average drug loading was 30.59%±2.45%,and the median diameter(ID 50)was 52.596μm±0.023%.[Conclusions]The encapsulation efficiency,drug loading and ID 50 of oregano oil chitosan microspheres prepared by emulsion crosslinking method met the requirements.The drug-loaded microsphere not only can be used as a preparation finished product for direct application,but also be used as a product intermediate to lay a foundation for the research and development of subsequent dosage forms.

Research Progress on the Preparation of Inorganic/Natural Materials Composite Microspheres

Microspheres are a new type of drug carrier with great potential for development and application.Natural polymers have good biocompatibility,biodegradability,and are easily dispersed in living organisms,making them suitable for preparing microspheres.Inorganic materials(mainly inorganic minerals)have excellent mechanical properties and are inexpensive and easy to obtain.Through the coupling and hybridization of natural polymers and inorganic materials,they can complement each other's advantages and synergistically enhance efficiency,resulting in many excellent physical and chemical properties.Inorganic materials/natural polymer composite microspheres can be prepared by modifying natural polymers with inorganic materials through various methods such as emulsification crosslinking,solution mixing,in-situ synthesis,extrusion,etc.The application of inorganic materials/natural polymer composite microspheres in drug delivery systems has significant sustained-release effects,is safe and non-toxic,and the cost of carrier materials is relatively low,which has certain significance for the development of new drug carriers.This article reviews the recent research on the preparation,drug loading and release properties of inorganic material/natural polymer composite microspheres,analyzes the advantages and disadvantages of commonly used preparation methods,and looks forward to the development direction of composite microspheres.

Preparation, Characterization and in Vitro Release of Ciprofloxacin Polylactic Acid Microspheres

Aim Ciprofloxacin polylactic acid microspheres (CFX-PLA-MS) were preparedusing solvent evaporation method from a solid-in-oil-in-water emulsion system. Methods Orthogonalexperiment was used to optimize the method of CFX-PLA-MS preparation. Microspheres werecharacterized in terms of morphology, size, encapsulation efficiency, drug loading and in vitro drugrelease. Results The physical state of CFX-PLA-MS was determined by scanning electron microscopy(SEM) and differential scanning calorimetry (DSC) . Microspheres formed were spherical with smoothsurfaces. Drug was enveloped in microspheres without mixing physically with PLA. The averageparticle size was 280.80 ± 0.15 μm, with over 90% of microspheres falling in the range of 250 -390 μm. The encapsulation efficiency was 65.8% ± 0.58% and the drug loading was 34.1% ± 0.51% .In vitro release study revealed a profile of sustained release of Ciprofloxacin from CFX-PLA-MS. Theaccumulated release percentage and half-life (T_(1/2) of Ciprofloxacin microspheres were 84.0% in53.2 h, and 31.9 h, respectively. Higuchi equation was Q= -0.0043 + 0.003 9 t^(1/2), r = 0.9941.Conclusion Ciprofloxacin microspheres have been successfully prepared and sustained release of CFXfrom microspheres is achieved.

Poly(lactic acid)-aspirin microspheres prepared via the traditional and improved solvent evaporation methods and its application performances

Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.

A review of recent progress in preparation of hollow polymer microspheres

The preparation methods of hollow polymer microspheres both at home and abroad are summarized, and their preparation mechanisms and developmental states are presented. These methods include the liquid droplet method, dried-gel droplet method, self-assembly method, microencapsulation method, emulsion polymerization method and the template method. Hollow polystyrene microspheres are the most extensively studied in the research of hollow polymer microspheres. Through comparison of the advantages and disadvantages of different preparation methods, it is concluded that microencapsulation method is most suitable for preparing polystyrene hollow microspheres.

Preparation of Adriamycin Magnetic Albumin Microspheres and Their Experimental Antitumor Effects in vitro and in vivo

The adriamycin magnetic microspheres (ADM-MAMs) were prepared by the heat-stabilized protein methods. Their physico-chemical properties were examined; their cytotoxicities against tumor cells in vitro were assayed by a modi-fied MTT method, and their effects were observed on the implanted gastric tumor in Wistar rats given ADM-MAMs via alimentary canal at the presence of the ex-ternal magnetic fields. The results showed that the ADM-MAMs were successful-ly prepared and had cytotoxic effect on tumor cells in vitro similar to the free ADM (P>0. 05). The inhibitory effects of ADM-MAMs on the implanted gastric tumor in vivo were significantly increased as compared with the controls (P<0.01). Our results suggested that ADM-MAMs were a new type of adriamycin (ADM) preparation and its form alteration did not affect its anticancer effects.

Controllable preparation of hierarchical NiO hollow microspheres with high pseudo-capacitance

Nickel oxide(NiO)hollow microspheres with hierarchical structure were fabricated through a process consisting of a self-assembling,hydrothermal reaction and calcination.The prepared NiO hollow microspheres composed of many nanoflakes,are about 2-3μm in diameter.The length of the NiO flakes,having clear edges,is about 500-700 nm,while the thickness is only about 40-50 nm.This indicates that the NiO microspheres possess a hierarchical structure that can provide porous channels to facilitate the transmission of both electrons and electrolyte ions.NiO microspheres exhibit a high specific capacitance of about 1340 F/g at a current density of 1 A/g and high capacitance retention about 96.5%after 1000 cycles.What’s more,the conductive mechanism of nickel oxide for electrochemical capacitor electrodes was also studied.

A supercritical CO_2 fluid technique for the preparation and evaluation of rhBMP-2-loaded PLLA microspheres

Introduction The use of supercritical fluids such as supercritical CO2（scCO2） has provided a ’clean’ and effective alternative to traditional methods of protein delivery systems.Here。

Fabrication of Porous Silica Microspheres Under the Assistance of Solid Template

Spherical porous silica microparticles were synthesized by a sol-gel process in the presence of porous CaCO3 particles, followed by removal of the carbonate templates. The resulting silica particles had very high porosity and wide pore size distribution, whose surface area and pore volume reached up to 367.3 m2/g and 0.72 mL/g, re- spectively. With a larger amount of the tetraethyl orthosilicate used, hollow silica microspheres were further obtained. Characterization was made to confirm the chemical and physical structures and purity of the silica microspheres. Spontaneous deposition of tetramethyl rhodamine isothiocyanate labeled dextran into the microspheres was also ob- served due to the charge attraction.

可膨胀微球制备方法和影响因素及应用进展

可膨胀微球是一种典型的单壁单芯的核-壳结构,由高分子聚合物壳和烷烃液体核组成。因其优异的发泡性能和可控的泡孔结构广泛应用于发泡剂等领域。然而,可膨胀微球的制备周期长、影响因素多且相互制约,导致其制备和研究困难。本综述总结了可膨胀微球的5种制备方法,概括了粒径、膨胀温度和膨胀倍率的影响因素,分析了性能调控的手段,分类总结了应用领域,尤其是热-机械转变特性的应用。最后对可膨胀微球的研究方向和发展前景进行了展望,以期望为可膨胀微球的持续研究提供参考。

基于液滴微流控技术的药物研发及研究进展

单分散性载药缓释微球作为新型药物释放系统,已成为缓释药物制剂研究的热点之一。传统制备方法获得的载药微球大多存在大小不均一、粒径分布宽、载药量低、缓释效果不明显等问题,极大地限制了其应用。液滴微流控技术是一种通过芯片微通道结构,实现在微尺度上对流体进行精细操控,形成高通量的结构和微液滴尺寸精确可调的新型制备工艺。微流控芯片作为微液滴技术的载体,可采用多种材料及制备工艺制备,以适用于不同种类的溶剂,进一步拓展其应用范围。通过微流控技术生产出的液滴具有体积小、尺寸均匀、封闭环境和内部稳定等特点,并能形成特定结构与功能的微球,在纳米材料、制药工程和生命科学等相关领域中具有巨大的应用潜力。相对于传统的微球制备方法,液滴微流控技术不仅可以构建多种形态的微球,还能提供优秀的模板,丰富和扩展微球的应用领域。以科学原理及应用实例为综述主线,概括了微液滴生成的机理及流道设计(包括T型通道法、流动聚焦法和共轴流法等),对不同结构形貌与特定功能的微球进行了归纳梳理(实心微球、Janus颗粒、核壳结构、多孔结构和不规则结构等),重点介绍了其在药物研发中的应用。通过对微液滴技术的研究现状的概括总结,提出了未来研究的方向及建设性意见。

二氧化硅空心微球的制备及应用研究进展

综述了二氧化硅(SiO_(2))空心微球的制备方法,包括模板法、斯托伯法(stober)制备法、微乳法、高温溶解法、喷雾反应法、超声波法等,对比了不同制备方法的优缺点。介绍了SiO_(2)空心微球在磁性材料、催化、生物医学、光电材料等多个领域的应用及发展前景。

微球制剂的研究进展

近年来,因生物可降解高分子材料制备的载药微球制剂可以进行缓控释放给药而备受关注,是当前高端新型药物制剂的研究热点。制备微球制剂的关键因素在于选择合适的高分子材料和生产工艺技术。然而,微球的制备工艺繁杂、质量控制困难,至今只在少数产品上应用,现在越来越多的口服难吸收的生物药物开始产品化,缓释微球在提高患者依从性方面备受瞩目。通过文献研究,对目前较为经典的微球制备技术和一些制备微球的新技术进行了综述分析,并总结了微球制剂的形态、大小及颗粒分布,载药量和包封率,释放度等质量评价相关成果,以期为微球制剂的研究提供一定的参考价值。

膜乳化工艺制备微球的应用进展

膜乳化工艺是一种重要的乳化分散技术,具有广泛应用前景。本文综述了膜乳化工艺在微球制备领域的工艺原理、制备方法和未来发展,并讨论了其在药物传递、化妆品和纳米材料制备等方面的应用进展。

Preparation of magnetic chitosan microspheres and its applications in wastewater treatment

The methods of preparation of magnetic chitosan microspheres have been introduced. In addition, their applications in the wastewater treatment, based on different kinds of wastewater, have been reviewed, and their mechanisms have been discussed.

Alprostadil liposome microsphere preparation stabilizes vascular plaques and inhibits intra-plaque inflammation

Background Vulnerable plaques play an important role in the onset of sudden cardiac events and strokes. How to stabilize vulnerable plaques is still a challenge to medical science. Alprostadil is a biologically active substance with strong activity on vessel. Our study assessed the stabilizing effects of an alprostadil liposome microsphere preparation （ALMP） on vulnerable plaques in the brachiocephalic artery of apolipoprotein E （Apo E） knockout mice. Methods Seventy-two male Apo E-knockout mice were fed a high-fat diet beginning at eight weeks of age. At week 17, they were divided randomly into groups for treatment with a high dose （3.6 μg, kg-1. d-1） or low dose （1.8 μg. kg-1 . d-1） of an ALMP, or 0.2 ml/d normal saline （control group）, The drug was administered using a micro-capsule pump. Twenty weeks after drug administration, pathological changes in the vulnerable plaques within the brachiocephalic artery were assessed, and levels of anti-mouse monocyte/macrophage monoclonal antibody （MOMA-2） and superoxide anions in the plaques were detected using immunofluorescence. The soluble intercellular adhesion molecule-1 （ICAM-1） expression was measured by ELISA, and the expression of matrix metalloproteinase-9 （MMP-9） and CD40 mRNA was measured using RT-PCR. Thrombospindin-1 （TSP-1） expression was detected using Western blotting. Results Compared with the control group, ALMP treatment significantly reduced the plaque area in the brachiocephalic artery （P 〈0.01）, significantly lowered the contents of the lipid core （P 〈0.01 ）, significantly reduced the number of ruptured fibrous caps （P 〈0.05）, and increased the thickness of the fibrous cap and significantly reduced the incidence of intra-plaque hemorrhage （P 〈0.05）. ALMP treatment significantly reduced the expression of MOMA-2, superoxide anion, MMP-9, ICAM-1 and CD40 in the plaques （P 〈0.01）, decreased plasma ICAM-1 expression （P 〈0.01 ）, and increased the expression of TSP-1. Conclusions Treatment with ALMP can stabilize vulnerable plaques by inhibiting inflammation.

Preparation and characterization of conducting polymer-coated thermally expandable microspheres

The thermally expandable microspheres（TEMs） were prepared via suspension polymerization with acrylonitrile（AN）, methyl methacrylate（MMA） and methyl acrylate（MA） as monomers and n-hexane as the blowing agent. Meanwhile, a novel type of functional and conductive thermal expandable microsphere was obtained through strongly covering the surface of microsphere by conductive polymers with the mass loading of 1.5%. The optimal conditions to prepare high foaming ratio and equally distributed microcapsules were investigated with AN-MMA-MA in the proportion of 70%/20%/10%（m/m/m）, and 25 wt% of n-hexane in oil phase. The further investigation results showed that the unexpanded TEMs were about 30 μm in diameter and the maximum expansion ratio was nearly 125 times of original volume. The polypyrrole（PPy） was smoothly coated on the surface of the TEMs and the expansion property of PPy-coated TEMs was almost the same as the uncoated TEMs. Moreover, the structure and expanding performance of TEMs and PPy-coated TEMs were characterized by scanning electron microscopy（SEM）, laser particle size analyzer and dilatometer（DIL）.

空心玻璃微珠制备技术及应用研究进展

综述空心玻璃微珠结构与发展历史,玻璃粉末法、喷雾造粒法、液滴法、干凝胶法、软化学法等空心玻璃微珠制备方法,在塑料、橡胶、树脂、乳化炸药、涂料、电磁屏蔽、微波吸收等方面的应用。提出空心玻璃微珠具备质量轻、强度高、流动性好,隔热、耐腐蚀等优点,在发展隔热、耐磨等复合材料中发挥越来越大的作用,在新能源产业和生物材料中的应用获得快速发展。认为在抗压强度、粒径等方面,空心玻璃微珠达不到高性能微珠的高强度和细粒径水准,微珠化学稳定性和精细化控制程度方面也有欠缺;在改进原料配方、优化生产工艺、提高后处理技术方面,以及针对全海深浮力材料、隔热涂料、乳化炸药等的应用方面应深入开展。

基于白及多糖多孔载药微球的制备与质量评价

目的 以白及多糖(BSP)为骨架材料制备糖尿病溃疡用多孔生物载药微球(Ms),并对其进行质量评价。方法 采用乳化-交联法制备载黄连素(BBR)的白及多糖微球(BBR-BSP-Ms),观察其外观形态、结构特点,评价粒径、载药量与体外释药行为等药剂学性质。结果 BBR-BSP-Ms处方和工艺:当BSP浓度为0.05%、BBR浓度为12%时,乳化时间为130min、交联温度为40℃、交联剂体积分数为11%、交联时间为70min、搅拌速度为960r·min^(-1)时,BBR-BSP-Ms粉末流动性好、互不粘连、分散性好,呈圆形、大小均匀,粒径分布为20~30μm,包封率为(86.92±0.03)%,载药量为(19.78±0.08)%;体外释药实验表明,BBR在48h内的累积释放率达82.12%,缓释效果良好。结论 以BSP为骨架材料载药微球工艺稳定可行,缓释效果明显,在糖尿病溃疡方面具有较好应用开发前景。