阿柔比星A聚乳酸毫微粒冻干针剂的研制及体外药物释放规律的研究

研究阿柔比星Ａ聚乳酸毫微粒（ＡＣＲＢ－Ａ－ＰＬＡ－ＮＰ）冻干针剂的制备,并对其体外释药进行考察。根据低共熔点测定结果,以及外观、色泽、再分散性等质量参数为指标,制备出ＡＣＲＢ－Ａ－ＰＬＡ－ＮＰ冻干针剂,采用动脉透析法研究其体个释放规律。结果,制得的ＡＣＲＢ－ＡＰＬＡ－ＮＰ冻干针剂色泽均匀,再分散性良好。其体外释药可用３种方式表达。提示ＡＣＲＢ－Ａ－ＰＬＡ－ＮＰ冻干针剂有明显的缓释特征。     

米托蒽醌聚乳酸缓释毫微粒冻干针剂在动物体内的靶向性研究

目的：比较肝靶向米托蒽醌聚乳酸缓释毫微粒（ＤＨＡＱ－ＰＬＡ－ＮＰ）冻干针剂和ＤＨＡＱ水针剂在小鼠体内的分布规律,验证前者的肝靶向性。方法：采用ＨＰＬＣ法测定静注ＤＨＡＱ－ＰＬＡ－ＮＰ和ＤＨＡＱ水针剂后小鼠血液、心、肝、脾、肺、肾的药物浓度,由此计算各器官的相对百分含量。结果：ＤＨＡＱ－ＰＬＡ－ＮＰ冻干针剂在肝脏的分布明显高于ＤＨＡＱ水针剂,在其它器官中的含量则低于水针剂,给药２４小时后药物在肝中的     

米托蒽醌聚乳酸缓释毫微粒冻干针剂的体外释药物特性研究

选择含１％维生素Ｃ的生理盐水作释药介质，用动态透析系统和分光光度法考察了不同分子量聚乳酸毫微粒冻干针剂的体外释药特性。分离子量聚乳酸毫微粒的释药速度明显慢于低分子量的聚乳酸毫微粒。通过选择适应分子量的聚乳酸制备毫微粒可控制其释药速度。     

阿柔比星A聚乳酸毫微粒主要性质研究

目的：对载药毫微粒主要质量指标载药量、包封率及其关系,粒径及其分布进行研究,方法：以阿柔比星Ａ聚乳酸微粒为研究对象,以分光光度测定载药量与包封率,以激光粒度分析仪测定粒径及其分布。结果：阿柔比星Ａ聚乳酸毫微粒平均载药量为１８．５％。平均包封率为８６．７％,平均数目径为８０ｎｍ,平均体积径为２３０ｎｍ。结论：载药量与包封率之间具有一定关系。体积径分布是载药毫微粒粒径分布评价不可忽视的内容。     

阿柔比星A毫微粒冻干针剂含量测定方法

本文建立了以四氢呋喃解毫微粒，用分光光度法与高效液相色谱法测定阿柔比星Ａ毫微粒冻干针剂中阿柔比星Ａ含量的方法，两种方法的回收率分别是９９．８４％与９９．６９％，供试品测定结果的日间变异系数分别是０．７４％与１．２％。两种方法对供试品测定结果一致，但以分光光度法更简便易行；对稳定性研究的供试品则因高效液相色谱法具分离测定的优点而更能真实反应含量变化情况。     

米托蒽醌聚乳酸缓释毫微粒冻干针剂的体外释药特性研究

选择含1％维生素C的生理盐水作释药介质，用动态透析系统和分光光度法考察了不同分子量聚乳酸毫微粒冻干针剂的体外释药特性。高分子量聚乳酸毫微粒的释药速度明显慢于低分子量的聚乳酸毫微粒。通过选择适宜分子量的聚乳酸制备毫微粒可控制其释药速度。     

柔红霉素毫微粒冻干针剂的研究

目的：制备易再分散、稳定的柔红霉素聚氰基丙烯酸正丁酯毫微粒（ＤＮＲ－ＰＢＣＡ－ＮＰ）冻干针剂。方法：选用适宜支架剂制得ＤＮＲ－ＰＢＣＡ－ＮＰ冻干针剂,并评价其相关理化性质。结果：冻干前后毫微粒形态、粒径、ｐＨ、包封率及载药量均无明显变化,含水量合格,再分散性良好,制剂稳定。其临界相对湿度为７５．３３％。结论：在适宜的处方及工艺条件下制备ＤＮＲ－ＰＢＣＡ－ＮＰ冻干针剂是可行的。     

阿克拉霉素A聚乳酸毫微粒冻干针剂在兔体内的血浆药动学研究

目的 :研究阿克拉霉素A聚乳酸毫微粒冻干针剂在兔体内的血浆药代动力学。方法 :采用HPLC法测定给药后的血浆药物浓度。结果 :经3p87药动学程序处理 ,得到两种制剂的药代动力学参数。结论 :与阿克拉霉素A相比 ,阿克拉霉素A聚乳酸毫微粒具有显著的缓释特性     

米托蒽醌聚乳酸缓释毫微粒针剂的制备

在单因素实验的基础上用均匀设计优化了米托蒽醌聚乳酸缓释微粒的制备方法。空白和载药微粒的平均粒径分别为１２９．９６和１３３．１５ｎｍ;包封率为９９．２３％;载药量为１３．５６％;制备收率为９９．３％。以乳和支架剂制得的冻干针剂外型美观、理化性质稳定,再分散后平均粒径为１５２．０２ｎｍ。用动态透析系统考察了不同分子量聚乳酸毫微粒冻干针剂的体外释药特性,结果显示高分子量聚乳酸微粒的释药速度明显慢于低分子     

阿克拉霉素A聚氰基丙烯酸异丁酯毫微粒冻干针剂体内外抗肝癌活性

阿克拉霉素Ａ聚氰基丙烯酸异丁酯毫微粒的冻干针剂，能明显抑制体外培养人肝癌细胞株７７０３的生长，ＩＣ５０为０．２８μｇ·ｍｌ－１。在０．８μｇ·ｍｌ－１浓度时，克隆形成抑制率为９０％，抑制作用有明显剂量依赖关系而未见明显时间依赖关系。静脉给药后，对常位移植人肝癌模型裸小鼠的抑瘤率为８６．８４％，肿瘤细胞增殖活性阳性率为２０．８３％。体内外均显示明显的抗肝癌活性，且体内抗肝癌活性比阿克拉霉素Ａ冻干针剂强。     

Freeze-drying of polycaprolactone and poly(D,L-lactic-glycolic) nanoparticles induce minor particle size changes affecting the oral pharmacokinetics of loaded drugs.

The present study was geared at identifying the conditions to stabilize poly (D,L-lactic-glycolic) (PLGA) and polycaprolactone (PCL) nanoparticles (NP) by freeze-drying with several cryoprotective agents. Differential scanning calorimetry and freeze-thawing studies were used to optimize the lyophilization process. These studies showed that all samples were totally frozen at -45 degrees C and evidenced the necessity of adding sucrose, glucose, trehalose or gelatine to preserve the properties of NP regardless of the freezing procedure. However, only 20% sucrose and 20% glucose exerted an acceptable lyoprotective effect on PLGA and PCL NP, respectively. Nonetheless, the final to initial size ratios ( approximately 1.5) indicated that particle size was slightly affected in both cases. In vivo studies with CyA-loaded PCL NP whose sizes matched those obtained after NP preparation (100 nm) and after being lyophilized (160 nm) showed that the changes of particle size might have some relevance on drug pharmacokinetics. The MRT was significantly (P<0.05) modified after an oral CyA dose of 5 mg/kg and the treatment with 160-nm sized CyA-loaded NP produced a higher drug partition into the liver of Wistar rats potentially affecting the toxic and immunosuppressive profile of the drug. Therefore, although the particle size changes induced by NP lyophilization were slight, they need to be carefully evaluated and cannot be neglected.     

In Vitro and In Vivo Investigation on PLA–TPGS Nanoparticles for Controlled and Sustained Small Molecule Chemotherapy

Purpose

The aim of this work was to evaluate in vivo poly(lactide)-d-α-tocopheryl polyethylene glycol 1,000 succinate nanoparticles (PLA–TPGS NPs) for controlled and sustained small molecule drug chemotherapy.

Methods

The drug-loaded PLA–TPGS NPs were prepared by the dialysis method. Particle size, surface morphology and surface chemistry, in vitro drug release and cellular uptake of NPs were characterized. In vitro and in vivo therapeutic effects of the nanoparticle formulation were evaluated in comparison with Taxol®.

Results

The PLA–TPGS NP formulation exhibited significant advantages in in vivo pharmacokinetics and xenograft tumor model versus the PLGA NP formulation and the pristine drug. Compared with Taxol®, the PLA–TPGS NP formulation achieved 27.4-fold longer half-life in circulation, 1.6-fold larger area-under-the-curve (AUC) with no portion located above the maximum tolerance concentration level. For the first time in the literature, one shot for 240 h chemotherapy was achieved in comparison with only 22 h chemotherapy for Taxol® at the same 10 mg/kg paclitaxel dose. Xenograft tumor model further confirmed the advantages of the NP formulation versus Taxol®.

Conclusions

The PLA–TPGS NP formulation can realize a way of controlled and sustained drug release for more than 10 days, which relieves one of the two major concerns on cancer nanotechnology, i.e. feasibility.     

Freeze-drying of polycaprolactone and poly( -lactic-glycolic) nanoparticles induce minor particle size changes affecting the oral pharmacokinetics of loaded drugs

The present study was geared at identifying the conditions to stabilize poly ( -lactic-glycolic) (PLGA) and polycaprolactone (PCL) nanoparticles (NP) by freeze-drying with several cryoprotective agents. Differential scanning calorimetry and freeze–thawing studies were used to optimize the lyophilization process. These studies showed that all samples were totally frozen at −45°C and evidenced the necessity of adding sucrose, glucose, trehalose or gelatine to preserve the properties of NP regardless of the freezing procedure. However, only 20% sucrose and 20% glucose exerted an acceptable lyoprotective effect on PLGA and PCL NP, respectively. Nonetheless, the final to initial size ratios (1.5) indicated that particle size was slightly affected in both cases. In vivo studies with CyA-loaded PCL NP whose sizes matched those obtained after NP preparation (100 nm) and after being lyophilized (160 nm) showed that the changes of particle size might have some relevance on drug pharmacokinetics. The MRT was significantly (P<0.05) modified after an oral CyA dose of 5 mg/kg and the treatment with 160-nm sized CyA-loaded NP produced a higher drug partition into the liver of Wistar rats potentially affecting the toxic and immunosuppressive profile of the drug. Therefore, although the particle size changes induced by NP lyophilization were slight, they need to be carefully evaluated and cannot be neglected.     

Albumin corona on nanoparticles – a strategic approach in drug delivery

Nanomaterials have been used widely for delivery of therapeutic agents. Protein–nanoparticle (NP) complexes have gained importance as vehicles for targeted drug delivery due to increased ease of administration, stability and half-life of drug, and reduced toxic side effects. Designing of phospholipid–bovine serum albumin (BSA) complexes and stealth NPs with BSA has paved the way for drug delivery carriers with prolonged blood circulation times. Preformed albumin corona has shown to decrease non-specific association and thereby reduce the clearance rate. Albumin corona has enabled the localization of drug carriers in specific tissues such as liver and heart, thus regulating biodistribution. Tailored albumin–NP conjugates have also enabled controlled degradation of NP and drug release. However, the binding of albumin with NP is associated with conformational and functional modulations in protein as observed with silver, gold and superparamagnetic iron oxide NPs. In this review, we highlight the various potential albumin–NP hybrids as nano drug carriers.     

Effect of conditions of preparation on the size and encapsulation properties of PLGA-mPEG nanoparticles of cisplatin

The effect of conditions of preparation on the size and encapsulation properties of PLGA-mPEG nanoparticles of cisplatin was investigated. A modified double emulsion method was applied for the preparation of PLGAmPEG nanoparticles of cisplatin, based on the partial or complete replacement of the water of the inner aqueous phase of the emulsion by dimethyl formamide(dmf) or the addition of cisplatin in the form of a complex with poly(glutamic acid). These modifications resulted in significant improvement of cisplatin loading in the PLGA-mPEG nanoparticles. Increased cisplatin loading and encapsulation efficiency were obtained when a relatively low dmf/water ratio, low dmf volume (when pure dmf formed the inner polar phase), or a high drug/polymer ratio were applied. A reduction of average size of nanoparticles was observed with decreasing the amount of PLGA-mPEG added in the formulation or increasing sonication time. The only factor that had a significant effect on size distribution was the sonication time, with the size P.I. being decreased with increasing sonication time. Prolonged sonication, however, decreased cisplatin loading and encapsulation efficiency. From the four lyoprotectant sugars tested (glucose, lactose, mannitol, and trehalose), only mannitol could prevent nanoparticle aggregation upon lyophilization. When appropriate amounts of an effective lyoprotectant were added in nanoparticles before lyophilization, drug loading of the nanoparticles was not affected by nanoparticle lyophilization.