Paclitaxel Micelles Research Articles

Co-delivery of TRAIL gene enhances the anti-glioblastoma effect of paclitaxel in vitro and in vivo

Co-delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and paclitaxel (PTX) is an attractive strategy to enhance their anti-tumor efficacy. As the most aggressive brain tumor, glioblastoma is sensitive to TRAIL and PTX. However, their therapeutic efficacy for intracranial glioblastoma is significantly impaired by blood–brain barrier (BBB) and blood–tumor barrier (BTB). Previously, we have prepared c(RGDyK)–poly(ethylene glycol)–polyethyleneimine (RGD–PEG–PEI) as a non-viral gene carrier for glioblastoma targeted therapy by employing a cyclic RGD peptide (c(RGDyK), cyclic arginine–glycine–aspartic acid–d-tyrosine–lysine), which binds to integrin αvβ3 over-expressed neovasculature and U87 glioblastoma cells with high affinities. In the present work, it was found that low concentration of paclitaxel (10nM) significantly enhanced the gene transfection of RGD–PEG–PEI/pDNA nanoparticle, which, in turn, dramatically elevated the anti-glioblastoma effect of paclitaxel in vitro. The gene transfection was also elevated in vivo. Co-delivery of brain-targeted CDX–PEG–PLA–PTX micelle dramatically enhanced gene transfection efficiency in the intracranial brain tumor. Due to the change of BBB integrity and the formation of BTB, we subsequently investigated the anti-glioblastoma effects of RGD–PEG–PEI/pORF-hTRAIL nanoparticle combined with CDX–PEG–PLA–PTX micelle (paclitaxel loaded CDX–poly(ethylene glycol)–block-poly(lactic acid) micelle). While at the same dosages, the median survival of the intracranial glioblastoma-bearing model mice treated with co-delivery (33.5days) is significantly longer than those of solely treated mice with CDX–PEG–PLA–PTX (25.5days), RGD–PEG–PEI/pORF-hTRAIL (24.5days) or physiological saline (21.5days). Herein, we verify the high potency of co-delivery of TRAIL gene and paclitaxel in the intervention of intracranial glioblastoma by employing tumor-targeted gene carrier RGD–PEG–PEI and brain-targeted micelle CDX–PEG–PLA, respectively.

Improving anti-tumor activity with polymeric micelles entrapping paclitaxel in pulmonary carcinoma

Nanoscale polymeric micelles have promising applications as drug delivery systems (DDS). In this work, to improve the anti-tumor activity and eliminate toxicity of the commercial formulation (cremophor EL and ethanol) of paclitaxel (PTX), we developed biodegradable poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles entrapping PTX by a simple one-step solid dispersion method, which is without any surfactants or additives and is easy to scale up. In addition, the PTX micelles could be lyophilized into powder without any adjuvant and the re-dissolved PTX micelles are stable and homogeneous. The prepared PTX micelles have a mean particle size of 38.06 ± 2.30 nm, a polydispersity index of 0.168 ± 0.014, a drug loading of 14.89 ± 0.06% and an encapsulation efficiency of 99.25 ± 0.38%. A molecular modeling study implied that PTX interacted with PCL as a core, which was embraced by PEG as a shell. The encapsulation of PTX in polymeric micelles enhanced its cytotoxicity by increasing the uptake by LL/2 cells. A sustained in vitro release behavior and slow extravasation behavior from blood vessels in a transgenic zebrafish model were observed in the PTX micelles. Furthermore, compared with Taxol®, the PTX micelles were more effective in suppressing tumor growth in the subcutaneous LL/2 tumor model. The PTX micelles also inhibited metastases in the pulmonary metastatic LL/2 tumor model and prolonged survival in both mouse models. Pharmacokinetic and tissue distribution studies showed that after PTX was encapsulated in polymeric micelles, the biodistribution pattern of PTX was altered and the PTX concentration in tumors was increased compared with Taxol® after intravenous injection. In conclusion, we have developed a polymeric micelles entrapping PTX that enhanced cytotoxicity in vitro and improved anti-tumor activity in vivo with low systemic toxicity on pulmonary carcinoma. The biodegradable MPEG-PCL micelles entrapping PTX may have promising applications in pulmonary carcinoma therapy.

Antitumor activity of folate-targeted, paclitaxel-loaded polymeric micelles on a human esophageal EC9706 cancer cell line

BackgroundEsophageal cancer is recognized as one of the most refractory pernicious diseases. In addition, it is an aggressive malignancy with a propensity for local progression and distant dissemination. Because of the poor long-term prognosis for patients with esophageal cancer, increasing attention has focused on the integration of targeted agents into current therapeutics. Nevertheless, there have been few studies reported concerning the therapeutic efficacy of paclitaxel-conjugated polymeric micelles in human esophageal cancer in vivo. Therefore, the aim of this research was to investigate the tumor inhibition effect of composite micelles containing folic acid and paclitaxel on the human esophageal EC9706 cancer cell line.Methods and resultsIntravenous administration of folate-targeted, paclitaxel-loaded micelles was demonstrated to be more efficient in inhibiting subcutaneous xenograft tumors and extending the survival rate of tumor-bearing nude mice than free paclitaxel and plain paclitaxel micelles at an equivalent paclitaxel dose of 20 mg/kg, which was further backed up by flow cytometry, TUNEL, and expression of apoptosis-related proteins, including Bax, Bcl2, and caspase 3 in this study.ConclusionThe folate-mediated paclitaxel-loaded polymeric micelle is a promising agent for the treatment of human esophageal cancer.

Anti-tumor Activity of Biodegradable Polymer-Paclitaxel Conjugate Micelles on H22 Liver Cancer Mice Models

Two kinds of paclitaxel (PTX) conjugate nanomicelles were prepared for cell apoptosis and anti-tumor activity evaluation on Lewis lung cancer mice models. One (PTX micelles) was prepared by self-assembling the PTX-conjugate co-polymer, poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate/PTX), and the other (FA-PTX micelles) was by co-assembling a mixture of the folic acid (FA)-carrying co-polymer poly(ethylene glycol)-b-poly(L-lactide-co-2,2-dihydroxylmethyl-propylene carbonate/FA) (PEG-b-P(LA-co-DHP/FA)), and the PTX-conjugate co-polymer. At 7 and 14 days after tail intravenous injection, the mice were killed. The inhibition rates of tumor growth for PTX and FA-PTX micelles were 50 and 90%, respectively, on the day 7, and 33 and 71%, respectively, on the day 14 after drug injection. Flow cytometry analysis showed that the cell apoptosis rates were 43, 54 and 72% for the control group, PTX micelles group and FA-PTX micelles group, respectively, on the day 7, and 16, 25 and 42 on the day 14. With the TUNEL assay, the grey values of PTX micelles and FA-PTX micelles groups were determined to be 61-62% and 43-44%, of that of the control group, on day 7 or day 14, respectively. Therefore, the PTX micelles and the FA-PTX composite micelles significantly inhibited the subcutaneously inoculated Lewis lung cancer and effectively induced the cell apoptosis, and the FA-PTX composite micelles displayed a better efficacy than the PTX-micelles, implying the contribution of the folate-mediated targeting and endocytosis effect. (C) Koninklijke Brill NV, Leiden, 2011

Anti-tumor Activity of Biodegradable Polymer-Paclitaxel Conjugate Micelles on Lewis Lung Cancer Mice Models

Two kinds of paclitaxel (PTX) conjugate nanomicelles were prepared for cell apoptosis and anti-tumor activity evaluation on Lewis lung cancer mice models. One (PTX micelles) was prepared by self-assembling the PTX-conjugate co-polymer, poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate/PTX), and the other (FA–PTX micelles) was by co-assembling a mixture of the folic acid (FA)-carrying co-polymer poly(ethylene glycol)-b-poly(L-lactide-co-2,2-dihydroxylmethyl-propylene carbonate/FA) (PEG-b-P(LA-co-DHP/FA)), and the PTX-conjugate co-polymer. At 7 and 14 days after tail intravenous injection, the mice were killed. The inhibition rates of tumor growth for PTX and FA–PTX micelles were 50 and 90%, respectively, on the day 7, and 33 and 71%, respectively, on the day 14 after drug injection. Flow cytometry analysis showed that the cell apoptosis rates were 43, 54 and 72% for the control group, PTX micelles group and FA–PTX micelles group, respectively, on the day 7, and 16, 25 and 42 on the day 14. With the TUNEL assay, the grey values of PTX micelles and FA–PTX micelles groups were determined to be 61–62% and 43–44%, of that of the control group, on day 7 or day 14, respectively. Therefore, the PTX micelles and the FA–PTX composite micelles significantly inhibited the subcutaneously inoculated Lewis lung cancer and effectively induced the cell apoptosis, and the FA–PTX composite micelles displayed a better efficacy than the PTX-micelles, implying the contribution of the folate-mediated targeting and endocytosis effect.

In vivo evaluation of novel chitosan graft polymeric micelles for delivery of paclitaxel

A water-insoluble anti-tumor agent, Paclitaxel (PTX) was successfully incorporated into polymeric micelles formed from new graft copolymers, N-octyl-N-(2-carboxyl-cyclohexamethenyl) chitosan derivatives(OCCC). The objective of this study was to optimize and characterize the novel PTX micelle (PTX-M). Furthermore, the pharmacokinetics, NIR-imaging, biodistribution, and anti-tumor effects of PTX-M were evaluated. The results showed that the PTX-M had high drug loading (43.25%). The Vd and t1/2β of PTX-M were increased by 11.4- and 2.83-fold, respectively, but the plasma AUC of PTX-M was 3.8-fold lower than that of Taxol. Biodistribution study indicated that PTX-M was widely distributed into most tissues, most of them found in liver, spleen, lung, and kidney. This result was similar with NIR(near-infrared)-imaging. Tumor growth was significantly inhibited after intravenous injection of PTX-M. PTX-M showed the enhanced anti-tumor effect and non-toxic effects compared with Taxol, the commercial product of PTX. Therefore, the chitosan-derived micelle system offered a stable and effective platform for cancer chemotherapy with PTX.

Synthesis and characterization of low-toxic amphiphilic chitosan derivatives and their application as micelle carrier for antitumor drug

A new series of amphiphilically modified chitosan molecules with long alkyl chains as hydrophobic moieties and glycol groups as hydrophilic moieties (N-octyl-O-glycol chitosan, OGC) was synthesized for use as drug carriers. The chemical structure was characterized by Fourier transform infrared, 1H nuclear magnetic resonance, and elemental analysis. OGC could easily self-assemble to form nanomicelles in an aqueous environment and exhibited a low critical micellar concentration of 5.3–32.5 mg/L. The biocompatibility and low toxicity of OGC as excipient for the dosage forms aimed at i.v. administration were confirmed by hemolysis, acute toxicity and histopathological studies. Furthermore, the possibility of solubilizing paclitaxel (PTX), a water-insoluble antitumor drug, with OGC micelles was also explored. PTX was successfully loaded into OGC micelles by using a simple dialysis process. The drug-loading capacity of OGC and stability of drug-loaded micelles were significantly affected by the degree of substitution of alkyl chains. Moreover, a series of safety studies including hemolysis, hypersensitivity, maximum tolerated dose, acute toxicity, and organ toxicity revealed that the PTX-loaded OGC micelles had advantages over the commercially available injectable preparation of PTX (Taxol ®), in terms of low toxicity levels and increased tolerated dose. Additionally, cytotoxicity studies showed that the PTX-loaded OGC micelles were comparable to the commercial formulation, but the blank micelles were far less toxic than the Cremophor EL vehicle. These results suggest that OGC is a promising carrier for injectable PTX micelles.

Comparative study of paclitaxel physically encapsulated in and chemically conjugated with PEG‐PLA

AbstractPaclitaxel‐loaded poly(ethylene glycol)‐b‐poly(l‐lactide (LA)) (PEG‐PLA) micelles were prepared by two methods. One is physical encapsulation of paclitaxel in micelles composed of a PEG‐PLA block copolymer and the other is based on a PEG‐PLA–paclitaxel conjugate, abbreviated as “conjugate micelles”. Their physicochemical characteristics, e.g. critical micelle concentration (CMC), morphology, and micelle size distribution were then evaluated by means of fluorescence spectroscopy, scanning electron microscopy (SEM), and dynamic light scattering (DLS). The results show that the CMC of PEG‐PLA–paclitaxel and PEG‐PLA are 6.31 × 10−4 and 1.78 × 10−3 g L−1, respectively. Both micelles assume a spherical shape with comparable diameters and have unimodal size distribution. Moreover, invitro drug delivery behavior was studied by high performance liquid chromatography (HPLC). The antitumor activity of the paclitaxel‐loaded micelles against human liver cancer H7402 cells was evaluated by 3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method. The conjugate micelles show a lower burst release during the initial stage and higher accumulative release amount of paclitaxel after a period of time while the encapsulated ones behave in the opposite way. Both the paclitaxel‐loaded micelles showed comparable anticancer efficacy with the free drug. Copyright © 2008 John Wiley & Sons, Ltd.

Paclitaxel Prodrugs with Sustained Release and High Solubility in Poly(ethylene glycol)-b-poly(ε-caprolactone) Micelle Nanocarriers: Pharmacokinetic Disposition, Tolerability, and Cytotoxicity

Develop a Cremophor and solvent free formulation of paclitaxel using amphiphilic block co-polymer micelles of poly(ethylene glycol)-b-poly(epsilon-caprolactone) (PEG-b-PCL) and characterize their release, solubility, cytotoxicity, tolerability, and disposition. Hydrophobic prodrugs of paclitaxel were synthesized via DCC/DMAP or anhydride chemistry to overcome the poor loading (<1% w/w) of paclitaxel in micelles of PEG-b-PCL. Micelles were prepared by a co-solvent extraction technique. A micellar formulation of paclitaxel prodrug (PAX7'C(6)) was dosed intravenously to rats (10 mg/kg) and compared to Taxol (paclitaxel in CrEL:EtOH) and PAX7'C(6) in CrEL:EtOH as controls at the same dose. Pharmacokinetic parameters and tissue distribution were assessed. Paclitaxel prodrugs had solubilities >5 mg/ml in PEG-b-PCL micelles. Resulting PEG-b-PCL micelles contained 17-22% w/w prodrug and were less than 50 nm in diameter. PEG-b-PCL micelles released paclitaxel prodrugs over several days, t(1/2)>3 d. Only the 7'derivative of paclitaxel with the shortest acylchain 7'hexonoate (PAX7'C(6)) maintained cytotoxic activity similar to unmodified paclitaxel. PAX7'C(6) micelles demonstrated an increase in area under the curve, half-life, and mean residence time while total clearance and volume of distribution decreased. Paclitaxel prodrugs in PEG-b-PCL micelle nanocarriers augment the disposition and increase tolerability making further studies on tumor efficacy warranted.

Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P1231

To investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic P123. The polymeric micelles of paclitaxel with Pluronic P123 were prepared by a solid dispersion method. The characteristics of micelles including particle size distribution, morphology and in vitro release of PTX from micelles were carried out. PTX-loaded micellar solutions were administered through the tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assess the pharmacokinetics and tissue distribution of PTX, respectively. Taxol, the commercially available intravenous formulation of PTX, was also administered as control. By using a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 25 nm with narrow size distribution and a spherical shape. PTX was continuously released from Pluronic P123 micelles in release medium containing 1 mol/L sodium salicylate for 24 h at 37 centigrade degree. In the pharmacokinetic assessment, t(1/2beta) and AUC of micelle formulation were 2.3 and 2.9-fold higher than that of Taxol injection. And the PTX-loaded micelles increased the uptake of PTX in the plasma, ovary and uterus, lung, and kidney, but decreased uptake in the liver and brain in the biodistribution study. Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.

Phase I dose escalation study of a polymeric micellar formulation of paclitaxel in patients (pts) with refractory non-hematologic cancer

2088 Background: Genexol-PM (G-PM) utilizes a low molecular weight, biodegradable, amphiphilic diblock copolymer, methoxy-poly(ethylene glycol)-block-poly(D,L-lactide) to form polymeric micelles of paclitaxel. G-PM does not contain Cremephor EL, thus has the potential for lower toxicities and administration of higher doses. Methods: G-PM was administered as a 3 hr intravenous infusion on day 1 of 21-day cycle. Dose cohorts were 85 mg/m2, 175 mg/m2, 290 mg/m2 and 435 mg/m2. Results: 23 pts were treated with doses of 85 mg/m2 to 435 mg/m2. 19 pts are fully evaluable, 6 male and 13 female, with a mean age of 54 years (33 to 78 years). Two pts experienced dose-limiting toxicities (DLTs), one pt with grade 3 diarrhea (290 mg/m2) and one with grade 3 febrile neutropenia (435 mg/m2). No cohort had 2 or more pts with DLTs thus the maximum tolerated dose (MTD) was not exceeded. The most common non-hematolgoic toxicities were fatigue (58%), constipation (47%), decreased appetite (42%), nausea (42%), dyspnea (37%), peripheral /sensory neuropathy (37%) and diarrhea (32%). Myelosuppression was uncommon and mild (anemia 21%, neutropenia and thrombocytopenia 5% each). The mean Cmax ranged from 713.67 (85 mg/m2) to 4510 ng/mL (435 mg/m2), mean half-life 11.06 to 17.20 hr, and mean total area under the curve (AUC0-∞) 2956.35 to 24812.78 ng · hr /mL. G-PM appeared to follow a three-compartment model, suggesting a slow flux of paclitaxel into the plasma from the peripheral tissues or “deep” compartment. Three pts had partial responses (PR). Two pts with refractory pancreatic cancer had decreases in CA 19–9, one of which had radiologic PR (96+ months). Conclusion: G-PM was well tolerated in doses up to 435 mg/m2 every 21 days. The MTD was not reached, however, due to a trend towards increased toxicities at the 435 mg/m2 the presumptive MTD and recommended dose for phase 2 is 435 mg/m2. No significant financial relationships to disclose.

Preparation and Characterization of Water-Soluble Prodrug, Liposomes and Micelles of Paclitaxel

Alternative formulations of paclitaxel were developed in order to improve its aqueous solubility, and characterized in vitro. A methacrylic acid based nanoconjugate of paclitaxel was synthesized by a simple esterification reaction with molecular weight of 1657 Da. The in vitro hydrolysis study on the prodrug of paclitaxel in presence of rat plasma has shown that the ester bond was quite stable (less than 1% of paclitaxel was liberated from prodrug in 24 h). This water-soluble prodrug was encapsulated into polyethylene glycol coated liposomes optimized with saturated lipids, to overcome the physical instability associated with paclitaxel. Under in vitro testing, prodrug liposomes seem very impressive with release of only 45% of payload in 180 h. Further, chemical as well as physical stability studies have shown that liposomes were stable without any signs of crystallization of paclitaxel. In addition, paclitaxel was covalently coupled to poloxamer via methacrylic acid linker to obtain a micelle forming conjugate. Evidence for self-assembly of this conjugate into micelles was provided by fluorescence spectroscopy, light scattering and differential scanning calorimetry techniques. Micellization of the conjugate was thermodynamically favored and the core of resulting micelles exhibited higher microviscosities (than poloxamer micelles). Release studies using dialysis technique along with high performance liquid chromatography revealed that paclitaxel is liberated from micelle in the form of methacrylic acid oligomer based prodrug in a gradual manner. These preliminary studies provided indication on the performance and feasibility of testing these carrier systems as a safer alternative to the Cremophor EL based paclitaxel formulation.

Polymeric micelles for delivery of poorly soluble drugs: Preparation and anticancer activity in vitro of paclitaxel incorporated into mixed micelles based on poly(ethylene glycol)-lipid conjugate and positively charged lipids

Paclitaxel-loaded mixed polymeric micelles consisting of poly(ethylene glycol)-distearoyl phosphoethanolamine conjugates (PEG-PE), solid triglycerides (ST), and cationic Lipofectin® lipids (LL) have been prepared. Micelles with the optimized composition (PEG-PE/ST/LL/paclitaxel=12/12/2/1 by weight) had an average micelle size of about 100 nm, and zeta-potential of about −6 mV. Micelles were stable and did not release paclitaxel when stored at 4°C in the darkness (just 2.9% of paclitaxel have been lost after 4 months with the particle size remaining unchanged). The release of paclitaxel from such micelles at room temperature was also insignificant. However, at 37°C, approx. 16% of paclitaxel was released from PEG-PE/ST/LL/paclitaxel micelles in 72 h, probably, because of phase transition in the ST-containing micelle core. In vitro anticancer effects of PEG-PE/ST/LL/paclitaxel and control micelles were evaluated using human mammary adenocarcinoma (BT-20) and human ovarian carcinoma (A2780) cell lines. Paclitaxel in PEG-PE/ST/LL micelles demonstrated the maximum anti-cancer activity. Cellular uptake of fluorescently-labeled paclitaxel-containing micelles by BT-20 cells was investigated using a fluorescence microscopy. It seems that PEG-PE/ST/LL micelles, unlike micelles without the LL component, could escape from endosomes and enter the cytoplasm of BT-20 cancer cells thus increasing the anticancer efficiency of the micellar paclitaxel.

In Vivo Pharmacokinetic and Tissue Distribution Studies in Mice of Alternative Formulations for Local and Systemic Delivery of Paclitaxel: Gel, Film, Prodrug, Liposomes and Micelles

The aim of this study was to increase the understanding on the pharmacokinetic and tissue distribution of paclitaxel as influenced by formulation approach. For this purpose, various formulations investigated in Swiss mice included liposomes, poloxamer 407 gel and chitosan film for subcutaneous route; and water-soluble methacrylate prodrug, liposomes and poloxamer micelles for systemic administration. During this study, the currently marketed formulation of Cremophor EL of paclitaxel was used as the reference. A highest plasma concentration following intravenous administration of paclitaxel was observed for rigid and 'Stealth((R))' liposomes containing the prodrug while, least was for covalently incorporated paclitaxel micelles. Further, poloxamer micelles demonstrated both the highest mean residence time of 7.34 h and volume of distribution (VSS=4.82 and VZ=5.87 L/kg) for paclitaxel. This was followed by prodrug loaded 'Stealth' liposomes, which showed a mean residence time of 4.96 h but were least distributed into apparent physiological volume (VSS=2.12 and VZ=3.16 L/kg). These results clearly signify the role of formulation/excipient in drug disposition and possible interactions. Importantly, due to decrease in the clearance rate of drug, the area under curve values of paclitaxel increased by 1.64- and 2.5-fold for micellar and prodrug loaded 'Stealth' liposomal formulations, respectively over reference formulation. While thermoreversible gels served to decrease plasma concentration of paclitaxel (8-fold) after subcutaneous administration, systemic levels were totally absent after implantation of films. In tissue distribution studies, maximum percent of paclitaxel was observed in liver for reference formulation, conventional liposomes and micelles whereas highest levels of prodrug and 'Stealth((R))' liposomes were in kidney and spleen, respectively. The novel formulations significantly altered tissue accumulation profiles of paclitaxel relative to the reference formulation, for example, reduction in uptake by heart from liposomes and micelles, as well as the major recognition mechanism for elimination. It is proposed that a combination therapy with liposomes and micelles of paclitaxel for systemic delivery along with implantation of chitosan film for local delivery, may serve not only to improve patient compliance by obliterating the need to administer Cremophor EL, but also increase patient survival.

Polymeric micelles of poly(2-ethyl-2-oxazoline)-block-poly(ε-caprolactone) copolymer as a carrier for paclitaxel

Polymeric micelles based on amphiphilic block copolymers of poly(2-ethyl-2-oxazoline) (PEtOz) and poly(ε-caprolactone) (PCL) were prepared in an aqueous phase. The loading of paclitaxel into PEtOz–PCL micelles was confirmed by 1H-NMR spectra. Paclitaxel was efficiently loaded into PEtOz–PCL micelles using dialysis method, and the loading content of paclitaxel in micelles was in the range 0.5–7.6 wt.% depending on the block composition of block copolymers, organic solvent used in the dialysis, and feed weight ratio of paclitaxel to block copolymer. The higher the content of hydrophobic block in the block copolymers, the higher the loading efficiency of micelles for paclitaxel. When acetonitrile was used as solvent, a higher drug loading efficiency was obtained than with THF. The loading efficiency decreased with increasing feed weight ratio of paclitaxel to block copolymer from 0.1:1 to 0.2:1. The hydrodynamic diameters of paclitaxel-loaded micelles were in the range 18.3–23.4 nm with narrow size distribution. The hemolysis test of PEtOz–PCL performed in vitro indicated that the toxicity of PEtOz–PCLs to lipid membrane was not significant compared with Tween 80, and was comparable to that observed with Cremophore EL. The proliferation inhibition activity of paclitaxel-loaded micelles for KB human epidermoid carcinoma cells was also evaluated in vitro. Paclitaxel-entrapped polymeric micelles exhibited comparable activity to that observed with Cremophore EL-based paclitaxel formulations in inhibiting the growth of KB cells.