姜黄素白蛋白纳米粒的制备与评价

目的:优化姜黄素白蛋白纳米粒的处方工艺并对其特性进行表征。方法:以牛血清白蛋白为载体、通过反溶剂沉淀法制备载姜黄素纳米粒,以粒径为评价指标优选制剂处方及工艺,并考察所得纳米粒的放置稳定性、饱和溶解度及体外溶出度。结果:当有机相和水相体积之比为1∶20、药物与白蛋白用量之比为1∶1.5、保护剂为0.5%(V/V)甘露醇时,所得纳米粒冻干粉平均粒径约为320 nm。其在水、p H 6.8、p H 7.4 PBS中的溶解度显著高于原料药及物理共混物,体外溶出更快,且冻干粉的放置稳定性优于纳米混悬液。结论:白蛋白纳米粒处方能够改善姜黄素的水溶性及溶出度,放置稳定性较佳。     

姜黄素固体脂质纳米粒的制备及表征

目的：制备姜黄素（Cur）固体脂质纳米粒（SLN）。方法：用薄膜超声法制备Cur-SLN,以mcur：m单硬脂酸甘油酯、m单硬脂酸甘油酯：m卵磷脂、聚山梨酯-80质量浓度、超声时间为考察因素,以包封率为指标,用正交试验优选处方,并考察其粒径分布、Zeta电位。结果：当mcur：m单硬脂酸甘油酯=1：3、m单硬脂酸甘油酯：m卵磷脂=1：2.5、聚山梨酯-80质量浓度2.5%、超声时间12min时,所制得的Cur-SLN平均粒径为（145.6±5）nm,Zeta电位为（-31.9±1.5）mV,包封率为（97.42±0.39）%,载药量为（7.92±0.05）%。结论：采用薄膜-超声法制备Cur-SLN可行,为开发姜黄素新型给药系统提供试验依据。     

姜黄素金属配合物的合成、表征和抗肿瘤活性研究

目的:合成和表征了4个姜黄素的金属配合物,并对其抗肿瘤活性进行初步的研究.方法:以姜黄素为配体合成其乙酰丙酮氧钒、锌、铜、锡的配合物,用红外光谱、紫外光谱、元素分析对配合物进行了表征,并进行体外抗肿瘤活性初步筛选.结果:合成了4个姜黄素的金属配合物,并确定其结构.结论:药理活性筛选结果表明,多个配合物对肿瘤K562,HL-60细胞有效,部分配合物显示了较强的抗癌活性.     

Preparation,characterization and antitumor activity evaluation of apigenin nanoparticles by the liquid antisolvent precipitation technique

The present work aimed to apply the liquid antisolvent precipitation (LAP) method for preparing the apigenin nanoparticles and thereby improving the solubility and bioavailability of apigenin. The different experimental parameters on particle size were optimized through central composite design (CCD) using the Design-Expert^® software. Under the optimum conditions, the particle size of the apigenin nanosuspension was about 159.2?nm. In order to get apigenin nanoparticles, the freeze-drying method was selected and the mannitol was used as a cryoprotectant. Then the solid state properties of the apigenin nanoparticles were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermo gravimetric (TG), and X-ray diffraction (XRD). The results obtained displayed that the apigenin nanoparticles exhibited near-spherical shape and could be transformed into an amorphous form. In addition, the dissolving test, the bioavailability in rats, and the antitumor activity were also studied. The experimental results showed that the solubility of the apigenin nanoparticles were about 29.61 times and 64.81 times of raw apigenin in artificial gastric juice and in artificial intestinal juice, respectively, and the apigenin nanoparticles showed higher dissolution rates compared to raw apigenin, and was about 6.08 times and 6.14 times than that of raw apigenin in artificial gastric juice and in artificial intestinal juice. The oral bioavailability of apigenin nanoparticles was about 4.96 times higher than that of the raw apigenin, but the apigenin nanoparticles had no toxic effect on the organs of rats. In addition, the apigenin nanoparticles had a higher inhibition to HepG2 cells by lower IC50 than that of raw apigenin.     

姜黄素聚乙二醇-聚己内酯纳米粒的药动学及其体外抗肿瘤作用

目的研究姜黄素聚乙二醇-聚己内酯纳米粒(Cur-PEG-PCL-NPs)在大鼠体内的药动学及其体外抗肿瘤作用。方法采用HPLC法考察Cur-PEG-PCL-NPs在SD大鼠体内的药动学行为;采用MTT法考察Cur-PEG-PCL-NPs体外对人肝癌细胞HepG2的抑制作用。结果姜黄素原药(Cur-Sol)和Cur-PEG-PCL-NPs在大鼠体内的药动学行为均符合二室模型,主要药动学参数分别为:Cur-Sol组t1/2α(7.76±1.80)min,t1/2β(20.11±5.30)min,AUC0→∞(248.59±25.31)mg·min·L^-1,CL(0.08±0.008)mL·min^-1;Cur-PEG-PCL-NPs组t1/2α(4.34±0.66)min,t1/2β(207.20±12.17)min,AUC0→∞(573.06±64.21)mg·min·L^-1,CL(0.04±0.004)mL·min^-1。体外抗肿瘤作用结果表明:Cur-PEG-PCL-NPs较Cur-Sol对HepG2细胞具有更强的抑制作用(P<0.01)。结论制备的Cur-PEG-PCL-NPs具有缓释特性,能延长血中滞留时间,且对HepG2细胞的抑制作用优于Cur-Sol,为后续肝癌治疗提供实验参考。     

Synthesis and antitumor activity of some curcumin analogs

In this study, four new curcurmin analogs (compounds 1, 2, 17 and 18) were synthesized. 17 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)N-methylpiperidone] showed high activity with GI50, TGI, and LC50 MG-MID values of 21.3, 70.7, and 97.7 microM, respectively. 18 [3,5-bis(4-hydroxy-3-methoxy-5-methylcinnamyl)-N-ethylpiperidone] showed the highest activity in this study with GI50, TGI, LC50 MG-MID values of 4.4, 33.8, 89.1 microM, respectively. 18 is even more active than curcumin with GI50, TGI, LC50 MG-MID values of 38.4, 35.6, 66.0 microM; respectively. 8 showed moderate selectivity towards Leukemia cell line-subpanel with a ratio of 5.6 (curcumin ratio: 1.2 for the same subpanel). The in vitro anti-tumor screening reveals that the results go hand in hand with the in vitro free radical scavenging effects. The antioxidant effect of these compounds depends mainly on the stabilization of the formed phenoxy free radical for which the p-hydroxy phenyl moiety is essential. o-substitution by electron-donating groups like the o-methoxy group (and to a even higher degree by the ethoxy group) increases the stability of phenoxy free radical, hence increasing both free scavenging and anti-tumor effects. Increasing the alkyl group chain on the N in the series of substituted N-alkyl piperidones as well as the extension of conjugation, increases the stabilization of phenoxy free radical and thereby the activity towards both free radical scavenging and anti-tumor effects. This may be attributed to an increased positive inductive effect and/or increased lipophilicity of the new compounds, a fact which is proven by the superior activities of compounds 17 and 18.     

Development and characterization of PLGA nanoparticles containing 1,3-dihydroxy-2-methylxanthone with improved antitumor activity on a human breast cancer cell line

Interest on xanthones has been growing considerably due to their broad spectrum of biological activities. 1,3-Dihydroxy-2-methylxanthone (DHMXAN) showed a significant inhibitory effect on the growth of MCF-7 cancer cells. DHMXAN-loaded nanosphere and nanocapsule formulations were prepared by the solvent displacement technique with the aim of improving the delivery of this poorly water-soluble compound. Moreover, we investigated the usefulness of this nanotechnology-based approach on the improvement of compound’s antitumor activity. Nanosphere and nanocapsule mean diameters ranged from 117?±?8 to 138?±?5?nm and from 266?±?7 to 286?±?22?nm, respectively, and both systems exhibited negative surface charge. Incorporation efficiency values of DHMXAN in nanospheres and nanocapsules were higher than 30% (30.9?±?3.3 to 38.8?±?3.6%) and 80% (85?±?7 to 88?±?6%), respectively. The release study of DHMXAN from nanocapsules suggests that drug release is mainly governed by its partition between the oil core and the external aqueous medium. The effect of different nanoparticulate formulations on the growth of human breast cancer cell line MCF-7 was evaluated using the sulforhodamine B (SRB) assay. Incorporation of DHMXAN in nanospheres and nanocapsules afforded a marked potentiation of the compound inhibitory effect.     

Preparation,characterisation and evaluation of curcumin with piperine-loaded cubosome nanoparticles

Abstract

Objective: In this study, curcumin was designed into the nanoformulation called cubosome with piperine in order to improve oral bioavailability and tissue distribution of curcumin. Methods: The characteristic of the cubosome was studied by using scanning electron microscope (SEM), Infrared spectrum and small angle X-ray scattering (SAXS) techniques. Tissue distribution of cubosome was measured by liquid chromatography-mass spectrometry (LC-MS) method in mice. Results: The characteristic of the cubosome was demonstrated that the curcumin and piperine were encapsulated in the interior of the cubosome and the crystal form was Pn3m space. The pharmacokinetic test revealed that the cubosome could improve the oral bioavailability significantly compared to the suspension of curcumin with piperine and be mainly absorbed by the spleen. Conclusion: These findings provide the reference to a preferable choice of the curcumin formulation and contribute to therapeutic application in clinical research.     

含氮姜黄素衍生物的合成及抗肿瘤活性研究

目的 合成具有新结构骨架的含氮姜黄素类抗肿瘤化合物并考察目标化合物的体外抗肿瘤活性.方法 以姜黄素和查耳酮为先导物,利用药效团和骨架迁越原理,设计并合成一系列含碱基的姜黄素类似物.选取人肺癌细胞(A-549)和人胃癌细胞(SGC-7901)对所合成的新化合物进行体外抗肿瘤活性筛选.并且用Discovery Studio...     

姜黄素聚合物胶束的制备及抗肿瘤活性评价

目的:制备姜黄素的维生素E聚乙二醇琥珀酸酯(TPGS)聚合物胶束,从而改善姜黄素的水溶性和抗肿瘤活性。方法:以TPGS为载体材料,采用薄膜水化法制备姜黄素胶束;以包封率和粒径为指标,考察水化温度、水化时间、药载比和水化体积的影响;以包封率、粒径、载药量为指标,经四因素三水平正交试验,确定姜黄素/TPGS胶束的最佳制备工艺;考察姜黄素/TPGS胶束的体外释放度;利用MTT法测试姜黄素/TPGS的体外抗肿瘤活性。结果:姜黄素/TPGS胶束的最佳药载比为1∶40,水化温度为60℃,水化时间为30 min,水化体积为6 mL;所得胶束平均粒径为11.02 nm, Zeta电位为-11.31,载药量为2.65%,包封率为96.20%;姜黄素/TPGS 48 h体外累积释放率为78%,具有一定的缓释性;MTT法表明,姜黄素/TPGS具有良好的抗肿瘤活性。结论:该文采用薄膜水化法制备了一种稳定的姜黄素/TPGS胶束,改善了姜黄素的水溶性,明显提高了其抗肿瘤效果。     

Generation and characterization of a novel tetravalent anti-CD22 antibody with improved antitumor activity and pharmacokinetics

The purpose of this study was to prepare a tetravalent anti-human CD22 recombinant antibody with improved antitumor activity and a half life longer than that of its divalent counterpart. We compared the ability of tetravalent vs. divalent antibody to associate/dissociate to/from CD22-positive Daudi cells, to interact with murine and human Fcgamma receptors (FcgammaR), to bind human complement component C1q, to inhibit the growth of tumor cells, to diffuse into various tissues, to be internalized by Daudi cells, to react with human neonatal Fc receptors (FcRn), and to persist in the circulation of normal mice. As compared to the murine or chimeric divalent antibodies, the chimeric tetravalent counterpart has a longer half life in mice. It also has an affinity for FcRns that is identical to that of human IgG. The tetravalent antibody has increased antitumor activity in vitro and completely conserved effector functions (binding to FcgammaR-positive cells and to C1q) in vitro. Despite its 33% higher molecular weight, it penetrates mouse tissues as well as its divalent antibody counterpart. Based on the improved in vitro performance and pharmacokinetics of the tetravalent antibody it will now be tested for its antitumor activity in vivo.     

In vivo antitumor activity of novel water-soluble taxoids

The antitumor activity of newly developed taxoids possessing a sugar moiety (glucose, galactose or mannose) to improve water solubility was evaluated. Galactose-bound taxoid (10-alpha-GAG-DT) proved superior to all other taxoids in both water solubility and antitumor activity. Therapeutic efficacy of 10-alpha-GAG-DT in terms of in vivo antitumor activity was found to be approximately equivalent to that of docetaxel, which is known to be superior to that of paclitaxel. The observation that the sugar moiety was gradually hydrolyzed in serum to release docetaxel indicates that 10-alpha-GAG-DT acts as a prodrug.     

Preparation,characterization, and antitumor activities of folate-decorated docetaxel-loaded human serum albumin nanoparticles

Abstract

Context: Docetaxel is now a major antitumor drug in clinical use for the treatment of a variety of tumors. The ethanol/Tween 80 solvent required in the formulation to increase the docetaxel solubility is at least partly responsible for the hypersensitivity reaction, decreased uptake by tumor tissue, and increased exposure to other body compartments.

Objective: The present study was aimed at developing hydrosoluble DTX-FA-HSANPs targeting tumor cells and to investigate antitumor activities of the nanoparticles.

Materials and methods: The DTX-HSANPs were prepared using a desolvation technique and the carboxylic groups of NHS-folate were conjugated with the amino groups of the human serum albumin nanoparticles, and studied their size and zeta potential, drug loading efficiency, surface morphology, release properties in vitro, and antitumor activities.

Results: The spherical nanoparticles obtained were negatively charged with a zeta potential of about ?30?mV and characterized around 150?nm with a narrow size distribution. Drug loading efficiency was approximately 17.2%. The folate-decorated nanoparticles targeted a human hepatoma cell line effectively. The in vitro drug release of DTX-FA-HSANPs in the first 96?h corresponded with the following equation: Q?=?18.87851???0.13866t?+?0.21276t^2???0.00704t³?+?0.0000847854t^4???0.00000034991t⁵ (R^2?=?0.98155). Moreover, the in vitro antitumor activities of DTX-FA-HSANPs were close to the activities of the positive control (docetaxel). The in vivo inhibition ratios of DTX-FA-HSANPs and docetaxel were 66.2% and 59.5%, respectively, at a dose of 5?mg/kg.

Discussion and conclusion: In light of the observed antitumor activities, it would be of considerable interest to collect sufficient data for the clinical application of docetaxel-loaded nanoparticles.     

Emodin loaded solid lipid nanoparticles: preparation, characterization and antitumor activity studies

The objective of the present study was to prepare and characterize emodin (EMO)-loaded solid lipid nanoparticles (E-SLNs) and evaluate their antitumor activity in vitro. EMO and pharmaceutical lipid material were used to prepare E-SLNs by high pressure homogenization (HPH). Poloxamer 188 and Tween 80 were used as surfactants. The physicochemical properties of the E-SLNs were investigated by particle size analysis, zeta potential measurement, drug entrapment efficiency (EE), stability and in vitro drug release behavior. The E-SLNs showed stable particle size at 28.6 ± 3.1 nm, ideal drug EE and relative long-term physical stability after being stored for 4 months. The drug release of E-SLNs could last 72 h and exhibited a sustained profile, which made it a promising vehicle for oral drug delivery. MTT assay showed that E-SLNs could significantly enhance the in vitro cytotoxicity against human breast cancer cell line MCF-7 and MDA-MB-231 cells compared to the EMO solution, while free EMO, blank SLNs (B-SLNs) and E-SLNs all showed no significant toxicity to human mammary epithelial line MCF-10A cells. Flow cytometric analysis demonstrated that E-SLNs also showed more significant cell cycle arrest effect in MCF-7 cells compared to bulk EMO solution. Hoechst 33342 staining and Annexin V-FITC/PI double staining further confirmed that E-SLNs induced higher apoptotic rates in MCF-7 cells, indicating that cell cycle arrest and apoptosis maybe the underlying mechanism of the enhanced cytotoxicity. Taken together, it seems that HPH was a simple, available and effective method for preparing high quality E-SLNs to enhance its aqueous solubility. Moreover, these results suggest that the delivery of EMO as lipid nanoparticles maybe a promising approach for cancer therapy.     

Preparation and characterization of intravenously injectable curcumin nanosuspension

The interest in nanosuspensions by the pharmaceutical industry is increasing given several nanosuspension products currently on the market for poorly soluble drugs. In this study, a novel dosage form for curcumin (CUR), CUR nanosuspension (CUR-NS), was successfully prepared by high pressure homogenization to improve CUR’s cytotoxicity, as well as improve its application via intravenous injection. Characterization of the CUR-NS was evaluated by morphology, size, zeta potential, solubility, dissolution rate, and crystal state of drug. The nanoparticles for CUR-NS presented a sphere-like shape under transmission electron microscopy with an average diameter of 250.6?nm and the zeta potential of CUR-NS was ?27.92 mV. Solubility and dissolution rate of CUR in the form of CUR-NS were significantly increased due to the small particle size and the crystalline state of CUR was preserved to increase its stability against degradation. Superior cytotoxicity in Hela and MCF-7 cells was obtained for CUR-NS compared with CUR solution. The safety evaluation showed that, compared with the CUR solution, CUR-NS provided less local irritation and phlebitis risks, lower rate of erythrocyte hemolysis. These findings suggest that CUR-NS may represent a promising new drug formulation for intravenous administration in the treatment of certain cancers.     

Preparation and characterization of intravenously injectable curcumin nanosuspension

The interest in nanosuspensions by the pharmaceutical industry is increasing given several nanosuspension products currently on the market for poorly soluble drugs. In this study, a novel dosage form for curcumin (CUR), CUR nanosuspension (CUR-NS), was successfully prepared by high pressure homogenization to improve CUR's cytotoxicity, as well as improve its application via intravenous injection. Characterization of the CUR-NS was evaluated by morphology, size, zeta potential, solubility, dissolution rate, and crystal state of drug. The nanoparticles for CUR-NS presented a sphere-like shape under transmission electron microscopy with an average diameter of 250.6?nm and the zeta potential of CUR-NS was -27.92 mV. Solubility and dissolution rate of CUR in the form of CUR-NS were significantly increased due to the small particle size and the crystalline state of CUR was preserved to increase its stability against degradation. Superior cytotoxicity in Hela and MCF-7 cells was obtained for CUR-NS compared with CUR solution. The safety evaluation showed that, compared with the CUR solution, CUR-NS provided less local irritation and phlebitis risks, lower rate of erythrocyte hemolysis. These findings suggest that CUR-NS may represent a promising new drug formulation for intravenous administration in the treatment of certain cancers.     

Preparation,characterization, and antibacterial activity of diclofenac-loaded chitosan nanoparticles

Emerging antibiotic resistance necessitates the development of new therapeutic approaches. Many studies have reported the antimicrobial activity of diclofenac sodium (DIC) and chitosan nanoparticles (CNPs). Hence, this study aimed to prepare non-antibiotic DIC-loaded CNPs (DIC.CNPs) and characterize their in vitro antibacterial activity. DIC.CNPs were prepared from low and high molecular weight (LMW and HMW, respectively) chitosan using an ionic gelation method. Prepared NPs were characterized, and their antibacterial activity against gram-positive Staphylococcus aureus and Bacillus subtilis was evaluated using the agar diffusion and broth dilution methods. The particle size, polydispersity index (PDI), and encapsulation efficiency of the formulated DIC.CNPs increased with increasing MW of chitosan. The prepared NPs showed a narrow size distribution with low PDI values (0.18 and 0.24) and encapsulation efficiency (29.3% and 31.1%) for LMW.DIC.CNPs and HMW.DIC.CNPs, respectively. The in vitro release profile of DIC from the DIC.CNPs was biphasic with a burst release followed by slow release and was influenced by the MW of chitosan. DIC.CNPs exhibited significantly higher antibacterial activity against S. aureus (minimum inhibitory concentration [MIC₉₀] _LMW.DIC.CNPs?=?35?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?18?µg/mL) and B. subtilis (MIC_{90 LMW.DIC.CNPs}?=?17.5?µg/mL and MIC_{90 HMW.DIC.CNPs}?=?9?µg/mL) than DIC alone did (MIC_{90 DIC}?=?250 and 50?µg/mL against S. aureus and B. subtilis, respectively). The antibacterial activity was influenced by pH and the MW of chitosan. Collectively, these results may suggest the potential usefulness of DIC.CNPs as non-antibiotic antibacterial agent necessitating further future studies to asses the stability of DIC.CNPs prepared.     

Preparation and characterization of paclitaxel-loaded DSPE-PEG-liquid crystalline nanoparticles (LCNPs) for improved bioavailability

Lipid-based liquid crystalline nanoparticles (LCNPs) have attracted growing interest as a new drug nanocarrier system for improving bioavailability for both hydrophilic and hydrophobic drugs. In this study, self-assembled LCNPs based on soy phosphatidyl choline and glycerol dioleate, which was known possessing low toxicity and negligible hemolysis, were prepared using poly(ethylene glycol)-grafted 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE-PEG) as the dispersing agent. Paclitaxel (PTX) was used as a model hydrophobic drug. The particle size of the optimized DSPE-PEG-LCNPs and PTX-loaded DSPE-PEG-LCNPs were around 70nm. Crossed polarized light microscopy was used to characterize the phase behavior of liquid crystalline (LC) matrices, which showed a fan-like birefringent texture in dark background indicating the coexistence of reversed cubic and hexagonal phase in the optimized LC matrix. Transmission electron microscopy and cryo-field emission scanning electron microscopy revealed its internal water channel and "twig-like" surface morphology. PTX-loaded DSPE-PEG-LCNPs exhibited a biphasic drug sustained release pattern with a relatively fast release at the initial stage and a sustained release afterwards. PTX-loaded DSPE-PEG-LCNPs presented higher AUC (410.942±72.522μg/Lh) when compared with commercial product Taxol (212.670±41.396μg/Lh). These results indicated that DSPE-PEG-LCNPs might serve as a potential sustained release system for poorly water-soluble agents.     

高载药量和厚朴酚纳米粒的制备及其抗肿瘤作用研究

目的 研究一种高载药量和厚朴酚纳米粒, 评价其对小鼠肝癌H22移植瘤的生长抑制作用。方法 用牛血清白蛋白(BSA)和聚乙烯吡咯烷酮(PVP)为辅料, 采用超声-沉淀法制备和厚朴酚纳米粒。建立H22肝癌皮下小鼠肿瘤模型, 以环磷酰胺注射液(CTX)为阳性对照, 考查ip给药后其对肿瘤的抑制作用。结果 和厚朴酚纳米粒呈球形, 平均粒径为(116.5±1.3)nm, 多分散指数(PDI)为0.116±0.001, 体外溶出较原料药大幅度提升。在H22荷瘤小鼠体内, 和厚朴酚纳米粒显示出剂量相关的抑瘤作用, 低、中、高剂量(10、20、40 mg/kg)组抑瘤率分别为52.57%、66.33%和71.24%。结论 和厚朴酚纳米粒对肿瘤有明显的抑制作用。     

Synthesis and evaluation of some water-soluble prodrugs and derivatives of taxol with antitumor activity.

The synthesis and evaluation of some 2'- and 7-amino acid derivatives of taxol (1) are reported. Reaction of taxol with N-protected amino acids gave 2'-N-protected amino acid esters of taxol. However, deprotection of the amino group and subsequent isolation of products were complex and only successful when formic acid was used to deprotect a t-BOC protecting group. Esterification of taxol using N,N-dialkylated amino acids gave 2'-amino acid esters of taxol, 2'-(N,N-dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol as its methanesulfonic acid salt (5b), in good yield. The 7-derivatives, 7-(N,N-dimethylglycyl)taxol (9) and 7-L-alanyltaxol (12), were prepared by two alternate methods. In the first approach, the 2'-hydroxyl group was protected using the [(2,2,2-trichloro-ethyl)oxy]carbonyl, or troc, protecting group followed by the esterification of the 7-hydroxyl and subsequent deprotection of the amino and troc groups. In the second approach, taxol was allowed to react with more than 2 molar equiv of the N-protected amino acids or N,N-dialkylated amino acids to give 2',7-diamino acid esters of taxol. For the protected amino acids, the deprotection of the amino group followed by removal of the 2'-substituent gave the 7-amino acid esters of taxol. The methanesulfonic acid salts of both 2'- and 7-amino acid esters showed improved solubility ranging from 2 to greater than 10 mg/mL. The 7-derivatives were effective in promoting microtubule assembly in vitro while 2'-derivatives showed little in vitro activity. The derivatives 2'-(N,N-dimethylglycyl)taxol (4) and 2'-[3-(N,N-diethylamino)propionyl]taxol (5) inhibited proliferation of B16 melanoma cells to an extent similar to that of taxol, while the other derivatives were about 50% as cytotoxic. In a mammary tumor screen, 2'-[3-(N,N-diethylamino)propionyl]taxol showed the greatest antitumor activity compared to the other analogues. The lower activities of the 7-derivatives in inhibiting tumor growth and melanoma cell proliferation (although they were almost as active as taxol in inducing microtubule assembly in vitro) may be due to differences in drug uptake by the cells. The similar cytotoxic and antitumor activities of the 2'-analogues and taxol can be explained by their conversion to taxol or an active taxol metabolite. Therefore, the 2'-analogues appear to behave as prodrugs and have the potential to be developed as chemotherapeutic agents.