异烟肼肺靶向性微球的制备及其小鼠体内分布

目的：制备异烟肼肺靶向性微球,评价其体外释药特性及在动物体内的肺靶向性。方法：采用溶剂挥发法制备微球,动态透析法考察其体外释药性能,实验动物静脉注射后测定其各组织的药物浓度,研究其体内相对分布百分率及肺靶向性。结果：制得的微球粒径在7～30μm的占微球总数的88．8％,平均粒径为（16.7±4．6）μm,包封率为86．92％,载药量为（40．7±3.6）％（n=5）,体外释药T50为68min,轻对照组延长了4.5倍。动物实验表明,制得微球后,药物在肺内的相对分布百分率明显高于其它组织与血液,并轻对照组提高了4倍。结论：本法制得的异烟肼微球具有明显的缓释性及肺靶向性。     

肺靶向阿奇霉素脂质体的制备及其在小鼠体内的分布

目的研究肺靶向阿奇霉素阳离子脂质体的制备方法并考察其在小鼠体内的分布。方法利用旋转薄膜-冻融法制备肺靶向阿奇霉素脂质体。用高效液相色谱法测定给药后小鼠体内各组织中的药物浓度。结果制得的脂质体平均粒径为6.582 μm，表面电荷为+19.5 mV，包封率大于75%，稳定性好。药物体外释药符合Higuchi方程。小鼠尾静脉给药后，阳离子脂质体主要被肺摄取，在肺部的滞留时间明显延长，AUC值约为阿奇霉素溶液的8.4倍。结论采用薄膜-冻融法，添加十八胺可制得具有较高包封率及稳定性的阿奇霉素阳离子脂质体，在小鼠肺部的分布优于注射液，能达到肺靶向目的。     

肺靶向羟基喜树碱脂质体的制备及其在小鼠体内的组织分布研究

目的： 研究羟基喜树碱脂质体的制备方法并考察其肺靶向及在小鼠体内的分布。方法： 采用薄膜分散－冻融法制备,添加D-甘露糖和十八胺修饰可得到肺靶向羟基喜树碱脂质体;用HPLC法测定给药后小鼠体内不同组织中的药物浓度。结果： 制得的脂质体平均粒径大于2 μm,表面电荷为+21.5 mV,包封率大于65%,稳定性好,符合要求。羟基喜树碱脂质体和注射液经小鼠尾静脉给药后,脂质体主要被肺摄取,在肺部停留的时间较普通注射剂显著延长,其相对摄取率r_e为60.72,脂质体组的肺靶向效率t_e为17.57。结论： 本实验制得羟基喜树碱脂质体具有较高包封率及稳定性,在小鼠肺部浓度高、滞留时间长,能达到肺靶向目的。     

肺靶向利福平聚乳酸微球的研究

在单因素考察的基础上进行正交试验设计,筛选出肺靶向利福平聚乳酸微球的最佳制备工艺条件;利用桨板法研究了微球的体外释药规律;考察了微球在不同温度下的稳定性;用新西兰兔为实验对象,研究了利福平聚乳酸微球的体内药动学及组织药物分布。结果制得的微球形态圆整,粒径在5～15μm范围内的占总体积的86.54%,微球平均粒径为9.00±4.08μm;包封率为31.9%;载药量为16.0%;体外释药方程为Q=20.77+10.12T_1/2(γ=0.9892);微球在冰箱4℃和室温(20～25℃)条件下性质稳定;体内实验表明微球具有长效和肺靶向双重作用。     

肺靶向硫酸链霉素明胶微球的制备

目的:用生物可降解材料明胶制备肺靶向硫酸链霉素明胶微球.方法:用乳化法制备微球,正交试验设计考察影响制备工艺的因素,用扫描电子显微镜观察微球表面形态,用红外光谱分析确证含药微球的形成.并对所制备的硫酸链霉素明胶微球的粒径及其分布、载药量、包封率、稳定性等进行了研究.结果:微球形态圆整,药物确己存于微球中.微球的平均粒径为12.269 μm,粒径在5.0～25.0 μm的微球占总数的91.5%,达到肺靶向要求.载药量为42.6%,包封率为53.8%.最佳工艺条件重现性好.经37℃、RH75%放置3个月,其含量、外观形态及大小基本不变.结论:该微球制备工艺稳定,可用于肺靶向注射剂的研究.     

柔性纳米脂质体构建肺部靶向给药系统的研究

目的 研究以胶体为核心的柔性纳米脂质体（flexible nano-liposomes,FNLs）包载蛋白类药物在肺部靶向递药的有效性和安全性。方法 应用注入法结合W/W乳化法制备FNLs,并通过制剂学方法检测FNLs的理化性质。通过肺部滴注insulin-FNLs,检测相应血糖值;将异硫氰酸荧光素经肺部滴注给药,评估FNLs经肺转运进入体循环后药物在肺泡的沉积情况;通过对肺组织进行苏木素-伊红染色,初步评价FNLs经肺部给药的安全性。结果 FNLs形态圆整,表面光滑,粒径为（153±0.94）nm,Zeta电位为-（20.9±0.21）mV;FNLs能增强降血糖效果,提高相对生物利用度,最低血糖值百分比可以达到（18.25±4.19）%。FNLs能延长药物在肺内的滞留时间,在肺部具有较好的耐受性。结论 FNLs作为肺部靶向递药载体,经肺部给药可以克服蛋白类药物肺内吸收屏障,增加生物利用度,为新型肺内给药系统的研发奠定基础。     

肺靶向卡铂明胶微球的研究

目的:为提高卡铂的疗效,降低毒副作用,制备了该药的明胶微球。方法:用乳化法制备卡铂明胶微球,紫外分光光度法测定药物的含量,二阶导数法测定体外释药情况;用静脉注射肿瘤细胞建立了肺肿瘤模型,计算瘤结节数来考察疗效。结果:卡铂明胶微球平均粒径为13-20 μm ,粒径范围5-0～28-6 μm 的微球数占总数的91-8% 。微球平均载药量为23-76%(n=3) 。冰箱、室温和37℃,RH75% 考察3个月,几乎无变化,体外释药符合一级动力学规律,释药T_1/2 比原药延长约10倍。药效学实验表明,卡铂明胶微球对小鼠肺部S180肿瘤生长有明显的抑制作用,抑瘤作用较原药卡铂大大提高。结论:卡铂明胶微球在体内有良好的肺靶向性,对提高药物的疗效,降低药物毒副作用等方面有重大意义。     

脑靶向3′,5′-二辛酰基-5-氟脲嘧啶脱氧核苷药质体研究

目的　为提高氟苷的脑靶向性,以增强疗效,降低毒副作用,制备其前体药物3′,5′-二辛酰基-氟苷的药质体。方法　用薄膜 超声分散法制备药质体,中心组合设计优化制备工艺,反向动态透析法测定体外释药情况,HPLC法测定小鼠iv后在体内各组织的分布。结果　药质体平均粒径为76nm ,载药量为29.02% ,包封率为96.62% ;体外释药过程符合双指数方程;以氟苷注射液为对照,药物在小鼠脑中靶向指数为对照液的10.97倍;并可显著延长药物在血液中的滞留时间。结论　氟苷酯化前体药物的药质体在体内有良好的脑靶向性,可作为新型的脑给药系统     

经内耳途径靶向脑给药的初步研究

本文探寻经内耳途径输送药物到脑部的可行性，为脑靶向给药提供一条崭新的研究思路。制备醋酸地塞米松(DA)固体脂质纳米粒(SLN)，建立相应的HPLC含量测定方法。经静脉和鼓室注射DA-SLN，并与地塞米松磷酸钠(DSP)溶液相比较，测定药物在脑脊液(CSF)和内耳外淋巴液(PL)中的浓度及药代动力学参数。结果表明，与静脉注射比较，鼓室注射药物在CSF的局部生物利用度显著提高，鼓室注射DA-SLN比静脉注射高2.5倍，鼓室注射DSP溶液比静脉注射高4.3倍。与DSP溶液比较，鼓室注射DA-SLN能明显增加进入CSF的药量和延长药物的作用时间，AUC和MRT分别较前者高13和19倍；并且药物在PL中分布减少，其AUC低76%。提示经内耳途径给药有望成为一种新的脑靶向方法，值得进一步研究。     

肺靶向卡铂囊泡的研究

目的制备卡铂非离子型表面活性剂囊泡,以提高卡铂对肺癌的疗效并降低其毒副作用。方法用薄膜分散法制备卡铂囊泡,紫外分光光度法测定药物的含量,二阶导数法测定体外释药。小鼠体内分布试验,用iv.S-180肿瘤细胞建立了肺肿瘤模型,计算瘤结节数。结果卡铂囊泡平均粒径为3.72μm,最小粒径为2.0μm,最大粒径为10.0μm,跨距为0.66。卡铂囊泡包封率为29.2%。体外释药符合双指数方程的规律,释药T_1/2比原药延长9.14倍。体内分布研究表明,卡铂囊泡与原药相比,有明显的肺靶向性。卡铂泡囊对小鼠肺脏S-180肿瘤生长较原药的抑瘤作用有明显提高。结论卡铂囊泡在体内有良好的肺靶向性。     

肝动脉栓塞米托蒽醌乙基纤维素微球的研究

利用正交实验设计法,优选适用于肝动脉栓塞的米托蒽醌乙基纤维素微球制备条件和工艺;采用动态透析法研究了该微球的体外释药规律;根据混悬液的稳定性理论,优选并制备了适于临床肝动脉介导栓塞使用的米托蒽醌乙基纤维素微球混悬注射液。结果表明∶在优化工艺条件下制得的米托蒽醌乙基纤维素微球外形圆整,球径在40～200μm范围内的占总数的91.9%,平均球径为110.24±38.19μm;包封率为55.6%;载药量为12.5%;体外释药符合单指数模型,释药方程为lg(Y_∞-Y)=-0.116t-1.198×10^-3(γ=0.9992,t₅₀=2.6h);其混悬液适于临床应用。用狗进行的实验表明肝血药浓度高,平均驻留时间比注射剂长2.45倍。     

Development of gelatin microspheres loaded with diclofenac sodium for intra-articular administration

We have previously reported on the targeting of diclofenac sodium in joint inflammation using gelatin magnetic microspheres. To overcome complications in the administration of magnetic microspheres and achieve higher targeting efficiency, the present work focuses on the formulation of gelatin microspheres for intra-articular administration. Drug-loaded microspheres were prepared by the emulsification/cross-linking method, characterized by drug loading, size distribution, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), gas chromatography, and in vitro release studies. The targeting efficiency of microspheres was studied in vivo in rabbits. The microspheres showed drug loading of 9.8, 18.3, and 26.7% w/w with an average size range of 37–46 µm, depending upon the drug–polymer ratio. They were spherical in nature and free from surface drug as evidenced by the SEM photographs. FT-IR, DSC, and XRD revealed the absence of drug–polymer interaction and amorphous nature of entrapped drug. Gas chromatography confirms the absences of residual glutaraldehyde. The formulated microspheres could prolong the drug release up to 30 days in vitro. About 81.2 and 43.7% of administered drug in the microspheres were recovered from the target joint after 1 and 7 days of postintra-articular injection, respectively, revealing good targeting efficiency.     

盐酸川芎嗪肺靶向微球的研究

用乳化法制备盐酸川芎嗪明肢微球,优化了工艺。对微球的外观、粒径与其分布、含量、体外释药、稳定性及体内分布等进行研究。结果表明平均粒径为12.65μm,粒径范围5.0～24.9μm占总数的87.5%,球内含药量平均为16.49%±0.49%(n=3),冰箱或室温放置稳定,体外释药符合一级动力学规律,释药t_1/2比原药延长约5倍。小鼠静注微球后20 min,在肺内的相对分布百分率明显高于其它组织与血液,与溶液对照组相比,提高近6倍。     

A Comparison of Two Methods for the Preparation Cefquinome-Loaded Gelatin Microspheres for Lung Targeting

Purpose

The aim of this study was to prepare CEQ-loaded gelatin microspheres and compare two preparation methods, evaluate targeting to the lungs.

Methods

Gelatin microspheres containing CEQ were prepared by an emulsion cross-linking method (ECLM) and a spray-drying method (SDM) and were characterized in terms of morphology, size, drug-loading coefficient, encapsulation ratio and in vitro release.

Results

The microspheres prepared by ECLM gave a drug loading (DL) of 19.4?±?2.4% and an entrapment efficiency (EE) of 80.8?±?3.2%. The microspheres prepared by SDM resulted in a DL value of 20.8?±?2.7% and an EE of 95.3?±?3.8%. The average particle size of microspheres was 7-30 μm by both methods and both preparations sustained CEQ release for 36 h in the target tissue (lungs). The in vitro release profile of the microspheres matched the Korsmeyer-Peppas release pattern. In vivo studies identified the lung as the target tissue and the region of maximum CEQ release. Histopathological examination showed a partial lung inflammation that disappeared spontaneously as the microspheres were biodegraded. In general, the formulations were safe.

Conclusion

The well-sustained CEQ release from the microspheres revealed its suitability as a drug delivery vehicle that minimized injury to healthy tissues while achieving the accumulation of therapeutic drug for lung targeting. The intravenous administration of CEQ gelatin microspheres prepared by SDM is of potential value in treating lung diseases in animals.

     

Targeted delivery of diclofenac sodium via gelatin magnetic microspheres formulated for intra-arterial administration

In the present work, we have attempted to deliver diclofenac sodium to a target site by intra-arterial injection of gelatin magnetic microspheres and subsequent localization using an external magnet. Drug-loaded magnetic microspheres were prepared by emulsification/cross-linking method, characterized by drug loading, magnetite content, size distribution, optical microscopy, scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), absence of glutaraldehyde by gas chromatography, and in vitro release studies. The targeting efficiency and the therapeutic efficacy of microspheres were studied in vivo in rabbits. The microspheres showed drug loading of 9.1, 18.7, 24.9% w/w, magnetite content of 27.8–28.9% w/w with an average size range of 25–30.6 μm, depending upon the drug–polymer ratio. They were spherical in nature as evidenced by optical microscopy and SEM. FT-IR, DSC, and XRD studies revealed the absence of drug–polymer interaction. Gas chromatography confirmed the absence of residual glutaraldehyde. The microspheres were able to prolong the drug release over 24–30 days and the application of sonication during in vitro release study has slightly increased the release rate. After intra-arterial administration of microspheres, 77.7% of injected dose was recovered at the target site which revealed good targeting efficiency. The microspheres effectively reduced joint swelling, but lesser extent than the oral diclofenac sodium in high dose, in antigen induced arthritic rabbits without producing gastric ulceration which was observed in rabbits treated with oral diclofenac sodium.     

肺靶向卡铂明胶微球的药物动力学和体内分布研究

采用原子吸收分光光度法测定静脉给药后小鼠血浆和各脏器组织中卡铂的浓度,并对肺靶向卡铂明胶微球和游离药物卡铂的药物动力学、体内分布行为和肺靶向性进行了比较研究。结果表明卡铂明胶微球药物动力学模型为三室模型,具有明显的肺靶向性。     

Preparation and Characterization of Oxybenzone-Loaded Gelatin Microspheres for Enhancement of Sunscreening Efficacy

The objective of our present study was to prepare and evaluate gelatin microspheres of oxybenzone to enhance its sunscreening efficacy. The gelatin microspheres of oxybenzone were prepared by emulsion method. Process parameters were analyzed to optimize the formulation. The in vitro drug release study was performed in pH 7.4 using cellulose acetate membrane. Microspheres prepared using oxybenzone:gelatin ratio of 1:6 showed slowest drug release and those prepared with oxybenzone:gelatin ratio of 1:2 showed fastest drug release. The gelatin microspheres of oxybenzone were incorporated in aloe vera gel. Sun exposure method using sodium nitroprusside solution was used for in vitro sunscreen efficacy testing. The formulation C₅ containing oxybenzone-bearing gelatin microspheres in aloe vera gel showed best sunscreen efficacy. The formulations were evaluated for skin irritation test in human volunteers, sun protection factor, and minimum erythema dose in albino rats. These studies revealed that the incorporation of sunscreening agent–loaded microspheres into aloe vera gel greatly increased the efficacy of sunscreen formulation more than four times.     

Controlled release of nifedipine from gelatin microspheres and microcapsules: in vitro kinetics and pharmacokinetics in man

Abstract

Nifedipine was embedded in a gelatin matrix to develop a prolonged release dosage form. The effects of polymer/drug ratio, size of the beads, cross-linking with formaldehyde and ethylcellulose coating of the gelatin microspheres on the in vitro release rate of the drug were investigated. The data were analysed according to different laws that can govern the release mechanism: first-order, Higuchi square root of time, spherical matrix and zero-order. The in vitro release kinetics of nifedipine from gelatin microspheres were mainly first-order; from formaldehyde hardened gelatin microspheres, complied with the diffusion model for a spherical matrix, and from ethylcellulose-coated gelatin microspheres, obeyed zero-order kinetics. These findings suggest the possibility of modifying the formulation in order to obtain the desired controlled release of the drug for a convenient oral sustained delivery system. The pharmacokinetic parameters of nifedipine, after adminstration of a single oral dose of nifedipine-loaded hardened gelatin microspheres to volunteers, suggest that the preparation can be considered as a sustained release delivery system for nifedipine.     

米托蒽醌白蛋白微球和联糖米托蒽醌白蛋白微球肝靶向性比较研究

目的：比较米托蒽醌白蛋白微球和联糖米托蒽醌白蛋白微球肝靶向性的优劣。方法：以小鼠为实验动物,以静脉注射给药后小鼠血浆及各器官中的米托蒽醌含量为指标。结果：联糖米托蒽醌白蛋白微球在肝中的分布高于米托蒽醌白蛋白微球,而且肝中米托蒽醌较高浓度的维持时间也更长。结论：联糖米托蒽醌白蛋白微球肝靶向性比米托蒽醌白蛋白微球好,但无统计学上的显著性差异。