聚乳酸载药微球的制备研究

聚合物微球的粒径较小,可以很好地越过阻碍物到达患病部位;并且通过控制药物的释放速率,能够实现准确给药,提高药物的利用率。聚乳酸具有良好的生物可降解性,在药物载体领域得到了广泛的应用。通过实验研究影响药物载体性能的各项因素,以硝苯地平为模型药物,采用乳化蒸发法制备载药微球,研究范德华力、药物的形态对微球和药物相容性的影响。结果表明,随着聚乳酸用量的不断加大,微球粒径逐渐增大;药物含量减少时,微球的表面光滑,且分散性较好;基于相容性规则可用于选择和设计适宜的药物载体的聚合物材料。     

药库型微型胶囊囊材研究进展

微包囊、微球作为一种新的药物释放体系,具有极大的发展潜力.药物载体是药物释放体系的重要组成部分,也是影响药效的主要因素.磁性微球、纳米胶囊的出现对囊材与载体材料的研究提出了新的要求.对药库型微型胶囊囊材与载体材料的研究现状与发展趋势进行了综述.     

聚己内酯/纳米羟基磷灰石复合微球中的药物分布及体外释放

采用单乳化溶剂挥发法制备了聚己内酯[poly(ε-caprolactone),PCL]/纳米羟基磷灰石(nano-hydroxyapatite,n-HA)复合微球.使用两种具有不同水溶性的模型药物对硝摹苯胺(p-nitroaniline)和罗丹明B(RhodamineB,RhB),研究n-HA在复合微球中的作用.用扫描电子显微镜观察微球的表面形貌.通过紫外-可见光分光光度法计算药物载量和包封率.用共聚焦激光显微镜分析药物在微球中的分布.分别研究了PCL微球和PCL/HA复合微球的体外释放性质.复合微球可以持续释放药物4周以上,在前3 d的突释后,其释放曲线符合Higuchi扩散方程.n-HA的加入使较亲水药物RhB在复合微球中分布更均匀,对较疏水药物对硝基苯胺则影响不明显.n-HA减少了载亲水药物的复合微球在前 3d 的突释,并减缓了其后的释放速率.结果表明:PCL/n-HA复合结构的材料有希望作为一种新的长效药物释放载体应用.     

5-氟尿嘧啶/明胶纳米载药微球的制备及体外性能研究

目的：以5-氟尿嘧啶(5-FU)为模型药物,明胶为载体材料,制备5-氟尿嘧啶/明胶纳米载药微球,探究药物的缓释效果和抗肿瘤性能。方法：“单凝聚相法”制备明胶纳米载药微球;透射电镜（TEM）和粒径分析仪（DLS）分析纳米微球的形貌、粒径分布情况;计算其包封率和载药量,并对其体外缓释效果和抗肿瘤性能进行研究。结果：明胶纳米微球的表面形态良好,分散均一,平均粒径65.1?2.1 nm,明胶纳米微球的包封率为23.5?1.9 %,载药量为69.7?0.5 %;明胶微球具有良好的缓释性能,Higuchi方程对微球的体外药物释放情况拟合度较高。四甲基偶氮唑蓝实验结果表明,5-FU/明胶微球对胃癌细胞(SGC7901)具有明显的抑制作用。结论：5-FU/明胶微球缓释性好,抗肿瘤活性显著,可作为抗癌药物的缓释制剂。     

一种新型的负载蛋白质药物微球的制备和释药性能

为了制备具有蛋白药物结肠靶向释放性能的新型药物载体,采用了水相溶液滴定反应法,分别以牛血清白蛋白(BSA)和乳铁蛋白(LF)为模型蛋白质药物,制得壳聚糖/纤维素磷酸钠(NaCS)/三聚磷酸钠(TPP)载药微球。利用电镜SEM和显微镜观测拍照,对微球的表面和截面形貌进行了表征,发现微球球形规则且颗粒大小均一。同时进行了体外药物模拟释放试验,考察了载药微球先后经过模拟胃液、模拟小肠液和模拟结肠液时的释药性能,及不同的释放条件和制造条件对于微球释药性能的影响,尤其考察了不同蛋白药物和不同干燥方式的影响。结果表明由临界点干燥法制得的负载乳铁蛋白(LF)微球在模拟胃液和小肠液释放量中5 h内只释放出不到20%的蛋白药物,而后在结肠模拟液中4 h内释放出蛋白药物80%以上。这些结果表明,壳聚糖/NaCS/TPP体系具有一定的作为结肠靶向药物释放载体的应用潜力。     

羧甲基壳聚糖离子配位微球的制备及性能研究

以羧甲基壳聚糖(CMCHS)为主要原料,采用静电脉冲液滴发生器制备羧甲基壳聚糖离子配位微球。光学显微镜观察微球具备规整形貌,扫描电镜分析显示干球粒径约为100μm且表面呈多孔结构;红外光谱证明其内部具有由CMCHS上的羧酸根与Ca^2 配位形成的羧酸盐结构。溶胀实验表明,CMCHS溶液浓度、金属离子种类及其浓度等制备条件均影响微球的溶胀性能．且其溶胀行为对pH值较敏感。药物体外释放初步研究表明,CaCl2浓度和释放介质pH值均对微球的释放性能产生影响。研究对其进一步应用于药物释放等领域具有重要意义。     

淀粉微球作为药物载体的应用研究进展

淀粉微球因具有无毒性、良好的生物相容性以及能被细胞吸收等优点,是生物医药领域药物载体研究热点之一.总结了国内外构建淀粉微球作为药物载体的研究成果,分析了淀粉微球中淀粉的来源主要有玉米淀粉、马铃薯淀粉、木薯淀粉等,概述了淀粉微球作为药物载体的应用,指出淀粉微球作为药物载体存在的问题及淀粉微球药物载体的发展前景和方向,旨在...     

改性淀粉微球的研究进展

淀粉微球成本低廉,本身无毒,具有较好的生物相容性、药物靶向性、优良吸附性等性能,在医药学、废水处理等领域都有应用。随着淀粉微球开发研究的深入,通过改性等手段开发性能更加优异的微球成为新的研究热点。本文综述了近些年改性淀粉微球的常用制备方法,介绍了改性淀粉微球作为药物载体和吸附剂在医药学、吸附领域的研究应用,以及微球目前普遍存在的问题,最后对改性淀粉微球研究方向进行了展望,指出通过引入新基团对淀粉或淀粉微球进行改性制备新型改性淀粉微球,可以增加微球适用性,拓宽其应用范围,应用在贵重金属的吸附回收中,将带来巨大的经济效益,而研发对贵重金属有良好吸附效果的改性淀粉微球也将成为重要的研究方向之一。     

壳聚糖载药微球的制备及其应用进展

壳聚糖具有生物相溶性、可生物降解、无毒、吸附等特性。壳聚糖作为药物缓释制剂已受到越来越多的关注,文章综述壳聚糖微球的制备方法及其在药物载体中的应用进展。     

基于纤维素模板的聚合物空心微球作为药物载体的性能研究及分析

以羟丙基纤维素为模板材料,分别采用不同的聚合方法制备了2种不同形态和结构的聚合物空心微球--聚N-异丙基丙烯酰胺-co-聚丙烯酸(PNIPAm-co-PAA)微凝胶和聚N-异丙基丙烯酰胺-聚丙烯酸(PNIPAm-PAA)水凝胶微囊。以盐酸阿霉素(Dox)作为模型药物,考察了聚合物空心微球作为药物载体的载药能力和体外释放性能。研究表明,PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊和Dox分子能够通过正负电荷的相互吸引实现有效结合;载药微球具有良好的缓释性能,并对Dox的释放表现出明显的pH值敏感性和温度敏感性。体外细胞毒性实验表明,载药PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊具有很高的抗肿瘤活性,细胞相对存活率均可达20%左右。PNIPAm-co-PAA微凝胶、PNIPAm-PAA水凝胶微囊在作为水溶性药物或蛋白类药物载体方面,具有潜在的应用价值,同时有望应用于木材胶黏剂防腐等。     

Release of indomethacin from a novel chitosan microsphere prepared by a naturally occurring crosslinker: Examination of crosslinking and polycation–anionic drug interaction

Novel chitosan microspheres with lower cytotoxicity were fabricated in this study and their drug release characteristics were investigated. Genipin, a naturally occurring crosslinking reagent that has been used in herbal medicine and in the production of food dye, was used to prepare crosslinked chitosan microspheres by a water‐in‐oil dispersion method. The crosslinking mechanism examined by FTIR and ¹³C–NMR suggests that the crosslinking of chitosan by genipin leads to the formation of secondary amide and heterocyclic amino linkage. The polycation–anionic drug interaction between chitosan and indomethacin was pH dependent and could affect the dissolution property of indomethacin. By examination of the release profiles of the crosslinked chitosan microsphere, it was found that the release of indomethacin from the microsphere was sustainable and influenced by factors such as crosslinking of microsphere and chitosan–indomethacin interaction, thus establishing crosslinked chitosan microsphere as a very promising polymeric carrier for drug release. © 2001 John Wiley & Sons, Inc. J Appl Polym Sci 81: 1700–1711, 2001     

Preparation of Single,Heteromorphic Microspheres,and Their Progress for Medical Applications

Microspheres applied in medical applications experience explosive development in recent years, such as drug release, cell culture, and bone tissue engineering, etc. However, there are still some bottlenecks both in economy and technology lay that cannot be ignored. For instance, microsphere technology has not been used in cell culture widely because of its uneconomical cost; as the core of drug-loaded microsphere, targeted microsphere technology is still not mature enough. Besides, the common microsphere fabrication methods: microfluidic or emulsion technology is difficult to guarantee high biocompatibility of microsphere due to utilization of photoinitiator, crosslinking agent, surfactant, and other substances. Therefore, gas-shearing technology has been proposed to solve these above shortcomings successfully. This paper focuses more on heteromorphic microspheres rather than on single microspheres which begins with a minute introduction of microsphere preparation methods: microfluidic, coaxial electrospray, emulsion, and gas-shearing technology. Then its medical applications: drug release, cell culture, bone tissue engineering, and hemostasis are discussed in detail. The disadvantages of fabrication methods and bottlenecks for medical applications at present are also stated. At the end, perspectives of microsphere development are put forward.     

The effects of different amounts of drug microspheres on the vivo and vitro performance of the PLGA/β-TCP scaffold

OIC-A006 (BMPs osteogenesis compounds), can stimulate bone marrow mesenchymal stem cells ALP, OPN, OC, Cbfal expression. To stimulate new bone formation in the body. We postulate different amounts of drug microspheres on the PLGA/β-CPT scaffold can produce the effects on performance and sustained release characteristics. In this paper, through adding different amount of carrier drug microsphere, three concentrations scaffolds which are 12.5, 18.75 and 25 μmol/L are prepared by adding different amounts of drug-loaded microspheres. Hereafter called OICM/CPT-200, OICM/CPT-300, OICM/CPT-400. We implant them in rat femur diameter 3 mm depth of 3 mm hole for eight weeks. The degradation, microsphere, delivery properties, with X-ray, micro-CT and histology are tested. Results show that the contain carrier drug microsphere scaffolds become radiopaque, and the gaps between the scaffold and radial cut ends are often invisible. This preliminary study reveals that different carrier drug microsphere has a corresponding effect the performance of stent body, OICM/CPT – 200 scaffolds induction effect is best. Illustrates that the low concentration load OIC-A006 microspheres can promote bone healing, and high concentration of OIC-A006 micro ball is played a inhibitory effect on bone healing process.     

聚乳酸/纳米四氧化三铁载阿奇霉素缓释剂的制备及性能研究

采用乳化-溶剂挥发法,以可生物降解材料聚乳酸为载体,在其中加入医药级阿奇霉素和一定量纳米四氧化三铁制备聚乳酸/纳米四氧化三铁载阿奇霉素缓释微球,通过正交实验优化了制备工艺,并研究了微球的释药行为.结果表明,微球具有明显的药物缓释作用.     

阿司匹林壳聚糖纳米缓释微球的制备及体外释放性能的研究

以自制阿司匹林为药物,壳聚糖为载体,采用乳化-化学交联法制备了阿司匹林-壳聚糖载药微球,确定了阿司匹林-壳聚糖载药微球的制备工艺条件,探讨搅拌速度、阿司匹林/壳聚糖质量比、交联剂戊二醛、乳化剂Span-80用量对微球的药物包封率、载药量和释药性能的影响。研究结果表明,室温条件下,以液体石蜡为介质,选用3%的壳聚糖冰醋酸溶液、按阿司匹林∶壳聚糖=1.5∶1、4%的戊二醛为交联剂、Span-80用量为体积比6%、中等搅拌速度制备出的微球药物包封率可达79%,微球粒径最小可达20 nm,制得的载药微球在16 h内对药物有良好的缓释作用,在25 h之内仍存在缓药效果。     

Preparation and the controlled release effect study of graphene oxide-modified poly(ε-caprolactone)

Functionalized graphene oxide-modified poly(ε-caprolactone) composites ((graphene oxide)GO/PCL) were successfully synthesized by Steglich esterification for drug applications of controlled release. Lomefloxacin (LMF) was selected as a model drug to investigate its controlled release properties. The controlled release effect of the LMF-contained pills of the GO/PCL and polylactic acid blend was evaluated. In contrast to the pure PCL, GO/PCL could effectively adjust the time of drug release and release the drug at a constant rate, achieving the controlled release requirements. Furthermore, different additive amounts of graphene oxide have different effects on adjusting the time of controlled release, while the best result obtained under the ratio is 4% GO/PCL as carrier of drug. Thus, high-quality drug carrier materials are obtained which are more suitable for clinical use. Exploring the optimum addition of graphene oxide is very significant for the development of GO/PCL carrier material.     

pH‐sensitive alginate/soy protein microspheres as drug transporter

The complex microspheres based on alginate (AL) and soy protein isolate (SPI) were prepared by solution blending and then Ca²⁺ crosslinking, and their function as drug carrier was explored as well. The effects of composition on the structures of microspheres were studied, and the XRD results proved the miscibility between components. Meanwhile, FTIR results suggested that such miscibility was driven by strong hydrogen bonding. Especially, the complex microsphere with equal content of AL and SPI had the best miscibility by morphological analysis, shown as a smooth and uniform surface of SEM images. The controlled release function of the complex microspheres was verified using theophylline as a drug model, that is, the swelling and drug release were affected by pH conditions and showed obvious differences under given pH of stomach, intestine, and colon. Moreover, the intestine and colon may be optimal site for prompt release of drugs. Except for the attribution of AL component to pH sensitivity, the complex microspheres also inherited the bioactivity of SPI component, which may lower irritants of drug to the tissues in body. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007     

Functionalized silver doped hydroxyapatite scaffolds for controlled simultaneous silver ion and drug delivery

Bacterial infections are a major problem in bone tissue regeneration, thus it is essential to incorporate antibacterial properties within the bone scaffolds. Silver compounds are frequently used as antibacterial agents to prevent bacterial infections and numerous studies have shown that silver ions can be incorporated within the biocompatible and osteoconductive biomaterial hydroxyapatite (HAp) structure, but, so far, no study has thoroughly evaluated silver ion release rates in long term. Therefore, we have established a novel carrier system for local drug delivery based on functionalized silver doped hydroxyapatite with determined long term silver ion release rates. Silver ions from prepared scaffolds were released with a rate of 0.001±0.0005 wt%/h taking into account the incorporated silver amount. Moreover, lidocaine hydrochloride was incorporated in the prepared scaffolds, to provide local anesthetic effect. These scaffolds were functionalized with sodium alginate and chitosan and in vitro drug release rate in simulated body fluid was evaluated. The results suggested that the developed novel composite scaffolds possess the antibacterial activity up to one year as well as controlled anesthetic drug delivery up to two weeks.     

Chitosan microspheres: modification of polymeric chem‐physical properties of spray‐dried microspheres to control the release of antibiotic drug

Antibiotic drug releasing from chitosan and acylchitosan microspheres was studied. The acylchitosan microspheres were prepared by modifying the microencapsulation process from spray‐drying to spray in‐liquid coagulating process for the improvement of chem‐physical properties of polymer in controlling the release of antibiotic drug. A higher yield of microspheres was recovered by this improved process. Crystallinity, swelling ability, and the morphology of various microspheres were investigated by X‐ray, water adsorption, and scanning electron microscopy studies. Results show that by modifying the microencapsulation process from spray‐drying to spray in‐liquid coagulating process, the chemical properties of the microsphere were varied from a hydrophilic chitosan microsphere to a hydrophobic acylchitosan microsphere, while the physical structure of the microsphere was varied from a porous chitosan microsphere to a dense acylchitosan microsphere. For the reasons, drug release rate of acylchitosan microspheres prepared by the novel spray microencapsulation method were apparently depressed, and the long‐acting release of antibiotic drug was possible to be achieved. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 71: 747–759, 1999     

Influence of Surfactant on the Characteristics of W1/O/W2-Microparticles

The water-in-oil-in water (W₁/O/W₂) double emulsion evaporation technique is widely used when the microencapsulation of soluble agents like naloxone HCl is intended. The present work shows the effect of HLB emulsifiers added to phase O on microsphere morphology, size, release, drug encapsulation efficiency. The addition of sorbitan ester to first emulsion (W₁/O) and the HLB of the surfactant have an important effect on the characteristics of poly-lactide-co-glycolide (PLGA) microparticles (MP). This MP with sorbitan esters added were smaller and released the hydrophilic drug, naloxone, with no-significant difference at pH 5 versus pH 7.5 (phosphate medium). This is an important fact when long-drug release is considered since it is known that PLGA degradation leads to media acidification. The HLB value had an important effect on drug loading. Sorbitan monooleate led to the highest naloxone loading. Because of its low HLB (4.3), it is most suitable for stabilizing the W₁/O emulsion, which is fundamental for the successful entrapment of a hydrophilic compound in MP prepared by double emulsion technique. Finally, drug solubility in the MP matrixes cannot be considered as a predictive parameter for drug encapsulation. Both surfactants increased the naloxone solubility in the polymer PLGA and only sorbitan monooleate increased the drug entrapment.