Evaluation of short-term effects of drug-loaded microspheres and traditional transcatheter arterial chemoembolization in the treatment of advanced liver cancer

BACKGROUND Liver cancer is a malignant tumor with high morbidity and mortality.Transcatheter arterial chemoembolization(TACE)is the main method for surgically unresectable liver cancer.In recent years,drug-loaded microspheres have been gradually applied in TACE technology.There are some controversies about the therapeutic effects of drug-loaded microspheres TACE(D-TACE)and traditional TACE.AIM To explore the short-term efficacy of D-TACE and traditional TACE in the treatment of advanced liver cancer.METHODS The clinical data of 73 patients with advanced liver cancer admitted to the First and Sixth Medical Centers of Chinese PLA General Hospital from January 2017 to October 2019 were retrospectively analyzed.Among them,15 patients were treated with D-TACE,and 58 patients were treated with traditional TACE.Clinical baseline characteristics,perioperative laboratory indices,postoperative adverse reactions and postoperative complications were compared between the two groups.RESULTS There was no statistical difference between the two groups for the postoperative response:The highest postoperative body temperature of the drug-loaded microsphere group was 38.0±0.9℃and the postoperative highest body temperature of the traditional TACE group was 38.3±0.7℃(t=-1.414,P=0.162).For the 24 h postoperative nausea and vomiting after surgery in terms of scoring and postoperative pain scores,the traditional TACE group was higher than the drugloaded microsphere group(χ2=14.33,P=0.014;χ2=32.967,P=0.000)and the two groups had significant statistical differences.The disease control rate at 3 mo after treatment in the drugloaded microsphere group was 60%and the disease control rate at 3 mo after treatment in the traditional TACE group was 75.9%(χ2=4.091,P=0.252).There was no statistical difference between the two groups of data.During the follow-up period,the number of interventional treatments received was once in the drug-loaded microsphere group and the traditional TACE group received an average of 1.48 treatments(χ2=10.444 P=0.005).There was a statistical difference between the two groups.CONCLUSION Compared with traditional TACE,D-TACE may have some advantages in the treatment of advanced hepatocellular carcinoma with a large tumor load in the short term,but the long-term clinical efficacy needs additional follow-up studies.In addition,compared with the traditional group,the patients in the drug-loaded microsphere group had better subjective tolerance and could reduce the number of interventional treatments.Therefore,D-TACE is worthy of clinical promotion.

In vitro properties of surface-modified solid lipid microspheres containing an antimalarial drug:halofantrine

Objective:To formulate and evaluate in vitro,surface-modified solid lipid microspheres containing hal of antrine using lipid matrix formed from goat fat and a phospholipid(P90H). Methods:The model drug,hal of antrine in an increasing concentration of 1%,2%,3%,4% and 5%w/w was incorporated into surface-modified solid lipid microspheres formulated by hot homogenization.Effect of drug concentration on the encapsulation efficiency was studied. The dispersion was evaluated using particle size,particle morphology,pH and encapsulation efficiency.The drug formulation with highest encapsulation efficiency was selected and used for the release studies and compared with the release from a commercial dosage form(Halfan~? 250 mg tablet,Claxo-Smithkline,Mayenne France) using simulated gastric fluid(SGF pH 1.2), simulated intestinal fluid(SIF pH 7.2) and phosphate buffer(pH 6.8) as biorelevant media. Results were analyzed statistically and the level of significance was taken to be P【0.05). Results:Discrete and spherical solid lipid microspheres were produced.The particle size of the dispersion was low(32.48-33.87μm) with minimal particle growth and high encapsulation efficiencies(86.8%-91.0%) after 3 months.The pH of the microspheres dispersion changed appreciably after 3 months.In vitro release result obtained revealed sustained and controlled drug release from the lipid microspheres compared with the tablet dosage form.Conclosions: Formulation of hal of antrine as solid lipid microspheres presents a better alternative to the conventional tablet formulation as the in vitro dissolution of the highly lipophilic hal of antrine was highly improved.

Preparation, stability and pharmacokinetics evaluation of lipid microspheres loading a promising antitumor candidate, Timataxel

Timataxel(13-(N-Boc-3-i-butylisoserinoyl-4,10-β-diacetoxy-2-α-benzoyloxy-5-β-20-epoxy-1,13-α-dihydroxy-9-oxo-19-norcyclopropa[g]tax-11-ene)), used to be called TM-2, is a novel semi-synthetic promising candidate for cancer treatment. However the preformulation study showed that TM-2 was insoluble and chemically instable in water, which would limit its application. This study aimed at the preparation of Timataxel lipid microspheres(TM-2 LMs)and investigated the difference between TM-2 LMs and TM-2 solution in pharmacokinetics. In this work, the final formulation was as follows: 0.10%(w/v) TM-2;10.00%(w/v) oil phase(long chain triglyceride:media chain triglyceride = 2.50%:7.50%);1.40%(w/v) phospholipid;0.02%(w/v) NaH2 PO4;2.25%(w/v) glycerin and water to a total volume of 100 ml.The particle size distribution, content and entrapment efficacy were 205.0 ± 43.3 nm, 101.00% and 99.12%, respectively. TM-2 LMs were stable during storage at 25 °C for 3 months, even under the condition of 60 °C and 4500 lx for 10 d. Phosphatidylethanolamine(PE) in phospholipid may contribute to the stability of TM-2 LMs. The pharmacokinetic parameters for TM-2 LMs were as follows: AUC(0-∞) 3663.71 μg/l h and the clearance 2.26 l/h/kg. As for solution, these parameters were 1712.52 μg/l h and 4.77 l/h/kg, respectively. The t1/2 of TM-2 LMs was similar to TM-2 solution. The pharmacokinetic results indicated that the AUC of TM-2 LMs was larger, the clearance was smaller than that of TM-2 solution. In a word, lipid microspheres were a promising drug delivery system for TM-2.

Efficacy and safety of transhepatic arterial chemoembolization with drug-loaded microspheres in unresectable primary liver cancer

BACKGROUND Transhepatic arterial chemoembolization(TACE),as a local treatment,has been widely used in the treatment of unresectable liver cancer.The introduction of drug carrier microspheres has brought new hope for the therapeutic effect of TACE.Microspheres can realize the slow release and directional delivery of drugs,reduce systemic toxicity and improve local curative effect.AIM To compare the effectiveness of traditional transcatheter arterial chemoembolization against microsphere-assisted transcatheter arterial chemoembolization in the treatment of hepatocellular carcinoma that is incurable.METHODS We searched the PubMed,Embase,Cochrane Library,and CNKI databases for clinical trials of drug-luting beads TACE(DEB-TACE)vs conventional TACE(cTACE)for the treatment of unresectable liver cancer.We screened references based on inclusion and exclusion criteria and then selected valid data for meta-analysis using RevMan 53 software.The complete response(CR)rate,partial response(PR)rate,postoperative stable disease(SD)rate,and 6-month and 12-month survival rates were compared.RESULTS A total of 12 articles were included,including 1177 patients,519 of whom received DEB-TACE and 658 of whom received cTACE.The CR rate in the DEB-TACE group was much greater than that in the cTACE group[relative risk(RR)=1.42,95%CI:1.18-1.72,P=0.0002].The 12-month survival rate significantly increased(RR=1.09;95%CI:1.01-1.17,P=0.03);the PR rate(RR=1.13;95%CI:0.97-1.30,P=0.12);the SD rate(RR=0.82;95%CI:0.64-1.05,P=0.12);and the 6-month survival rate(RR=1.05;95%CI:1.00-1.10,P=0.07).There was no significant difference(P<0.05).CONCLUSION Compared with those of iodized oil TACE,the drug-loaded microspheres tended to have therapeutic advantages.

Development of composite PLGA microspheres containing exenatide-encapsulated lecithin nanoparticles for sustained drug release

This study aimed to prepare poly(D, L-lactic-co-glycolic acid) microspheres(PLGA-Ms)by a modified solid-in-oil-in-water(S/O/W) multi-emulsion technique in order to achieve sustained release with reduced initial burst and maintain efficient drug concentration for a prolonged period of time. Composite PLGA microspheres containing exenatideencapsulated lecithin nanoparticles(Ex-NPs-PLGA-Ms) were obtained by initial fabrication of exenatide-loaded lecithin nanoparticles(Ex-NPs) via the alcohol injection method,followed by encapsulation of Ex-NPs into PLGA microspheres. Compared to Ms prepared by the conventional water-in-oil-in-water(W/O/W) technique(Ex-PLGA-Ms), Ex-NPs-PLGAMs showed a more uniform particle size distribution, reduced initial burst release, and sustained release for over 60 d in vitro. Cytotoxicity studies showed that Ms prepared by both techniques had superior biocompatibility without causing any detectable cytotoxicity.In pharmacokinetic studies, the effective drug concentration was maintained for over 30 d following a single subcutaneous injection of two types of Ms formulation in rats, potentially prolonging the therapeutic action of Ex. In addition, administration of Ex-NPs-PLGA-Ms resulted in a more smooth plasma concentration-time profile with a higher area under the curve(AUC) compared to that of Ex-PLGA-Ms. Overall, Ex-NPs-PLGA-Ms prepared by the novel S/O/W method could be a promising sustained drug release system with reduced initial burst release and prolonged therapeutic efficacy.

Efficacy of transcatheter arterial chemoembolization using pirarubicin-loaded microspheres combined with lobaplatin for primary liver cancer

BACKGROUND Drug-eluting beads show good safety and promising efficacy when used as part of a transarterial chemoembolization regimen for primary liver cancer.However,data on the clinical efficacy and safety of pirarubicin-loaded beads combined with lobaplatin are lacking in China.AIM To evaluate the efficacy and safety of transcatheter arterial chemoembolization using pirarubicin-loaded beads combined with lobaplatin for primary liver cancer.METHODS Between January 2019 and March 2020,60 patients with primary liver cancer were selected at Hebei North University Affiliated First Hospital.According to different treatment methods,the participants were categorized into two groups with 30 patients treated with pirarubicin-loaded microspheres combined with lobaplatin included in an observation group and 30 patients treated with pirarubicin emulsion with lipiodol combined with lobaplatin were included in a control group.The progression-free survival,overall survival,clinical response rate,disease control rate,liver and kidney function and adverse reactions were compared between the two groups.RESULTS The progression-free survival was 14 mo in the observation group,which was significantly higher than 9 mo of the control group(P<0.05).The 6-mo,12-mo and 18-mo survival rates were 93.33%(28/30),66.67%(20/30)and 23.33%(7/30),respectively in the observation group,which were significantly higher than 83.33%(25/30),50.00%(15/30)and 13.33%(4/30),respectively,of the control group(all P<0.05).The clinical efficacy rate and disease control rate were 73.33%and 93.33%,respectively,in the observation group,which were significantly higher than those of the control group(53.55%and 80.00%,respectively,all P<0.05).There was no significant difference in alpha-fetoprotein between the two groups before the treatment(P>0.05).After the treatment,alpha-fetoprotein was 289.06±76.21 ng/m L in the observation group and 365.01±73.11 ng/m L in the control group,which were low in both groups compared with those before the treatment(all P<0.05).The incidence of nausea and vomiting was significantly lower in the observation group than in the control group(P<0.05).There was no significant difference for the adverse reactions of pain and fever between the two groups(P<0.05).CONCLUSION The combination of pirarubicin-loaded beads and lobaplatin can improve treatment efficacy resulting in mild liver function damage and postoperative complications in patients with primary liver cancer.It can be used in clinical practice.

氟比洛芬酯脂微球注射液对癌症疼痛镇痛效果的临床观察

目的:观察氟比洛芬酯脂微球载体注射液(商品名凯纷)治疗癌痛的疗效和副作用。方法:38例未使用阿片类药物的中重度癌性疼痛患者每天静脉注射50mg/5m l氟比洛芬酯脂微球载体注射液,分别就其疗效、生活质量改善情况以及不良反应等方面进行评价。结果:氟比洛芬酯脂微球载体注射液治疗中重度癌痛的有效率为71.05%,生活质量改善情况治疗前后有显著差异(P<0.05)。但未见一般非甾体类药物常见腹痛、消化道出血等副作用;也未见便秘、恶心、呕吐、嗜睡等阿片类药物常见不良反应。结论:氟比洛芬酯脂微球载体注射液治疗中重度癌痛疗效可靠,生活质量可得到改善,不良反应发生率较低,可部分作为临床候选药品或口服吗啡替代药。

氟比洛芬酯脂微球载体注射液治疗中度术后疼痛的Ⅱ期临床试验

目的：考察氟比洛芬酯脂微球载体注射液对中度术后疼痛患者的止痛效果及安全性。方法：采用多中心随机双盲对照试验设计。试验药和对照药分别为氟比洛芬酯脂微球载体注射液和安慰剂。选骨科、普通外科和妇科术后中度疼痛(疼痛强度4-6)的受试者197例，试验组99例，对照组98例。试验组与对照组均单次给药，缓慢静脉注射1支(5mL)。用药前及用药后6h内评价疼痛强度(PI)、疼痛强度差(PID)、疼痛缓解率(PAR)和有效率。结果：试验组单次用药后6h的PI，PID和PAR分别为1．3，4．1，98．0％，显效率为89.9％；对照组则分别为3．3，1．7，43．9％，25．5％，2组比较差异有显著性(P<0．01)，氟比洛芬酯脂微球载体的镇痛效果明显优于安慰剂。结论：氟比洛芬酯脂微球载体注射液是安全有效的中等强度靶向镇痛药。

前列地尔注射液临床用药分析

目的：调查本院前列地尔注射液的使用情况,分析其临床使用的适宜性。方法：对2013年8月-2014年8月的3681例使用前列地尔注射液成人患者的分布情况、原患疾病及用法用量、疗程、药液使用时间、溶媒使用量、药物利用指数（DUI）进行统计分析。结果：前列地尔注射液在各科室使用广泛,3 681例患者使用中49.8%存在超说明书适应证、10.3%的患者超剂量、13.6%的患者药液使用时间过长、1%患者使用疗程过长、67.7%的患者使用溶媒量超说明书推荐等情况。结论：前列地尔注射液不规范使用情况需引起重视。对于前列地尔注射液存在的用药情况,医院应该制定前列地尔注射液使用规范,使前列地尔注射液的适应证、用法用量、疗程、药液使用时间、溶媒使用量等方面进一步优化。

氟比洛芬酯注射液的药理作用及临床应用

氟比洛芬酯注射液是氟比洛芬的脂微球制剂，能有效缓解术后疼痛和癌症疼痛，并且能避免口服制剂的不 良反应。概述氟比洛芬酯注射液的药理作用和临床应用。

呋喃二烯脂质微球在小鼠体内的药动学及组织分布研究

考察了呋喃二烯(FDE)脂质微球在小鼠体内的药动学及组织分布.制备FDE脂质微球并考察其粒径、Zeta电位、含药量等指标.小鼠尾静脉给药,采用HPLC法测定血浆和组织中的FDE浓度,评价药动学及组织分布特征.结果表明FDE脂质微球各项指标均符合注射剂要求.FDE在血浆中Cmax为(33.38±5.13)μg.mL-1,脑组织可检测到Cmax为(23.35±1.20)μg.g-1,说明FDE脂质微球可透过血脑屏障,对治疗脑部肿瘤及疾病具有潜在优势.

蟾酥脂质微球注射液对四种荷瘤裸鼠肿瘤生长的抑制作用

目的:观察蟾酥脂质微球注射液对荷人肝癌HepG2、人食管癌EC9706、人结肠癌HCT-8和人胃癌BGC 803瘤株裸鼠肿瘤生长的抑制作用。方法:在BALB/c-nu裸鼠右前肢腋下接种4种人癌细胞株建立荷瘤动物模型,移植10 d后采用均衡法随机分为5组,即蟾酥脂质微球注射液高剂量组(2.50 mg/kg)、中剂量组(1.25 mg/kg)、低剂量组(0.63 mg/kg)以及阳性药组(氟尿嘧啶注射液,1.25 mg/kg)和阴性对照组(等体积脂质微球空白注射液),每组7只裸鼠,给药体积0.2 ml。采用尾静脉注射方法给药,各组动物于分组后每周给药2次,连续给药6次。于给药后动态检测并计算各组肿瘤体积(V_t)、肿瘤相对体积(V_(RT))、肿瘤增殖率(T/C),末次给药后3 d检测并计算各组肿瘤质量和抑瘤率。结果:各组裸鼠给药前肿瘤体积均无显著性差异。荷人肝癌HepG2细胞瘤裸鼠给药7 d后,各剂量组肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),末次给药后中、高剂量组T/C值<40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为74.07%。荷人食管癌EC9706瘤裸鼠末次给药后,各剂量组肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),中、高剂量组T/C值<40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为70.38%。荷人结肠癌HCT-8细胞瘤裸鼠末次给药后,各剂量组肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),高剂量组T/C值<40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为52.42%。荷人胃癌BGC 803细胞瘤裸鼠末次给药后,中、高剂量组的肿瘤体积和相对肿瘤体积均较阴性对照组明显降低(P<0.05),各剂量组T/C值>40%,各剂量组的平均肿瘤质量均较阴性对照组明显降低(P<0.05),高剂量组的抑瘤率为47.42%。结论:蟾酥脂质微球注射液具有确切的抑制人肝癌HepG2、食管癌EC9706、结肠癌HCT-8和胃癌BGC 803瘤株增殖的作用,作用效果以抑制人肝癌HepG2和人食管癌EC9706瘤株生长作用为最佳。

蟾酥脂质微球注射液的制备及其灭菌稳定性

目的研究蟾酥脂质微球注射液的处方工艺并考察制剂的灭菌稳定性。方法采用两级高压均质法制备蟾酥脂质微球注射液,分别考察油相组成、乳化剂用量、pH、灭菌方式对制剂灭菌稳定性的影响。结果采用质量分数为10.00%的油相[注射用中链脂肪酸甘油酯(MCT)与注射用大豆油(LCT)等比例混合],质量分数为1.20%的豆磷脂,质量分数为0.06%的油酸钠,均质前调节pH6.5,采用100℃旋转水浴灭菌30 min,制备所得的蟾酥脂质微球注射液在灭菌后仍保持良好的物理化学稳定性。结论粒子界面荷电性、空间位阻作用、pH、灭菌方式是影响蟾酥脂质微球注射液的物理化学稳定性的重要因素。

去甲斑蝥酸钠脂质微球在大鼠体内的组织分布

目的比较去甲斑蝥酸钠脂质微球注射液与溶液型注射液在大鼠体内组织中的分布特征。方法大鼠股静脉注射去甲斑蝥酸钠脂质微球注射液,采用HPLC-MS法测定不同时间点大鼠组织脏器中的药物浓度。结果与去甲斑蝥素注射液相比,脂质微球注射液在肝脏组织中具有较高的浓度,肝脏相对分布率由16.3%增加至32%,AUC值为218.72 mg.L-1.h-1。而在心脏、肾脏、血液中的药物分布均无明显的变化。结论将去甲斑蝥酸钠制备成以脂质微球载药,使其在体内分布具有肝脏靶向性,从而在一定程度上提高了药物对肝癌及肝硬化的治疗效果。

卡巴他赛脂质微球注射液容器内残氧量对制剂稳定性影响

目的考察卡巴他赛脂质微球(cabazitaxel lipid microsphere,CTX-LM)注射液容器内残氧量对制剂稳定性的影响,并讨论制剂中药物的降解机制。方法在加速条件下,测定药物含量,制剂粒径、p H值、残氧量、全氧化值等指标。结果残存氧对卡巴他赛固体原料药无降解作用,40、60和80℃加速10 d的含量质量分数分别为99.8%、99.8%和99.9%,残氧量无明显变化;高温条件下卡巴他赛水溶液药物含量质量分数降低至40.4%,但与残存氧无关。对于卡巴他赛脂质微球注射液,高温下低氧组制剂氧化程度小于高氧组,且化学稳定性更好,降解活化能分别为62.6 k J·mol-1和56.1 k J·mol-1。其机制为磷脂的不饱和脂肪酸侧链经残存氧氧化断裂,产生酸性氧化产物使体系p H值下降,加剧了卡巴他赛在弱酸条件的水解,且残存氧越多、温度越高时,药物降解越显著。结论控制容器内残氧量有助于提高卡巴他赛脂质微球注射液的稳定性。

氟比洛芬酯脂微球在大鼠和比格犬体内的药动学及组织分布和排泄研究

目的:研究氟比洛芬酯脂微球在大鼠和比格犬体内的药动学以及在大鼠体内的组织分布和排泄情况。方法:分别静注给予大鼠2 mg/kg和比格犬1 mg/kg氟比洛芬酯注射液,采用LC-MS/MS法测定给药后不同时间大鼠和比格犬血浆、组织液和排泄物中氟比洛芬的含量,并用统计矩法得到大鼠和比格犬体内的药代动力学参数。结果:静注给予大鼠和比格犬氟比洛芬酯注射液后所得到的主要药代动力学参数分别为:AUC0-∞:(43.00±6.26)和(651.53±175.89)mg·L^(-1)·h^(-1),CL:(0.047±0.007)和(0.002±0.001)L·h^(-1)·kg^(-1),t_(1/2):(5.39±0.50)和(87.18±28.58)h,MRT_(0-∞):(7.04±0.46)和(118.20±30.12)h,VZ:(0.110±0.067)和(0.119±0.068)L/kg。静注给予大鼠氟比洛芬酯注射液后,药物迅速而广泛地分布于各组织中,但组织中的药物浓度相对于血浆中较低。大鼠静脉注射给予氟比洛芬酯注射液后36 h内只有0.23%±0.10%的药物通过尿液排出体外。结论:静注给药后,氟比洛芬酯注射液在大鼠和比格犬体内的消除半衰期与氟比洛芬的其他剂型相比明显延长,说明该剂型可以延长镇痛作用的持续时间,同时药物在组织中的分布较少也可以有效地降低非甾体类抗炎药对胃肠道的副作用。

水飞蓟宾脂质微球的制备及在大鼠体内的药物动力学考察

目的制备水飞蓟宾脂质微球并对其理化性质及大鼠体内药物动力学特征进行考察,为水飞蓟宾的临床应用提供理论依据。方法采用高压均质法制备水飞蓟宾脂质微球;分别采用动态光散射法、超速离心法考察制剂的粒径、zeta电位及药物的相分布;以自制水飞蓟宾溶液剂作为参比制剂,采用HPLC法考察大鼠体内药物动力学。结果制剂平均粒径约为192.4 nm,zeta电位为-24.56 mV,约77.5%的药物分布在油水界面膜上;40℃加速实验10 d,药物的相分布无变化;4℃留样观察6个月内稳定;水飞蓟宾脂质微球和溶液剂的药时过程均符合双隔室模型;非隔室模型分析结果表明,脂质微球和溶液剂的AUC0-t分别为(1.90±0.29)、(2.07±0.44)mg.h.L-1,两制剂药-时曲线相似。结论所制备的水飞蓟宾脂质微球性质稳定,大部分药物分布在油水界面膜上;脂质微球未改变药物在大鼠体内的药物动力学特征。

磁性前列地尔脂微球靶向治疗大鼠腹部皮瓣缺血再灌注损伤的基础研究

目的:探讨磁性前列地尔脂微球靶向治疗大鼠腹部皮瓣缺血-再灌注损伤的作用机制及疗效。方法:制备大鼠腹部皮瓣缺血再灌注损伤的动物模型,实验组注射磁性前列地尔脂微球,并在皮瓣外覆盖铷铁硼稀土磁铁;对照组注射生理盐水;空白组不进行血管阻断及药物注射。测定三组皮瓣血流量、皮瓣组织丙二醛和一氧化氮含量;皮瓣原位缝合后7d评估皮瓣成活率,并检测皮瓣组织中血管内皮生长因子的表达情况。结果:与对照组及空白组比较,在皮瓣缺血-再灌注过程中实验组皮瓣微循环血量明显增多、皮瓣组织内一氧化氮水平升高、丙二醛水平降低,差异有统计学意义(P<0.05);皮瓣原位缝合7d后皮瓣成活率显著提高(P<0.05)。结论:本实验制备的具有磁场顺应性的前列地尔脂微球可有效提升缺血-再灌注皮瓣部位的药物浓度、改善皮瓣微循环、降低缺血-再灌注损伤,进而提高皮瓣成活率。

氟比洛芬酯脂微球注射液临床应用新进展

氟比洛芬酯脂微球注射液是一种新型非甾体类抗炎镇痛药,由脂微球和其所包裹的氟比洛芬酯组成。脂微球对其所包裹的药物具有靶向性,控制包裹药物的释放,易于跨越细胞膜从而促进药物吸收,进一步缩短起效时间。氟比洛芬酯脂微球注射液已用于围术期镇痛、癌性疼痛等。本文综述其药理作用和临床应用新进展。

酒石酸长春瑞滨脂质微球注射液对荷人乳腺癌裸鼠肿瘤生长的影响

目的：研究酒石酸长春瑞滨脂质微球注射液（NVB-lip）对荷人乳腺癌裸鼠肿瘤生长的影响。方法：35只雌性BALB/c-nu裸鼠,随机分为NVB-lip高（10 mg/kg）、中（5 mg/kg）、低（2.5 mg/kg）剂量组,阳性对照组（酒石酸长春瑞滨注射液,5 mg/kg）和阴性对照组（脂质化空白溶液）,每组7只。给裸鼠接种人乳腺癌BCAP-37瘤株,待成瘤后,每只动物每次按0.20 mL经尾静脉注射给药,间隔3-4 d注射1次,每周注射2次,共注射6次。在第1次注射后第4、7、11、14、18和23天时分别称小鼠体质量和测量肿瘤体积,计算得出相对肿瘤体积、相对肿瘤增殖率和肿瘤抑制率。结果：与阴性对照组相比,各组荷瘤裸鼠体质量差异均无统计学意义（P均〉0.05）。NVB-lip各剂量组的相对肿瘤体积和相对肿瘤增殖率显著减小,肿瘤抑制率显著增大,差异均有统计学意义（P〈0.01）。结论：NVB-lip在2.5-10 mg/kg范围内抑瘤作用明显,具有可开发潜力。