Biological fate and interaction with cytochromes P450 of the nanocarrier material, d-α-tocopheryl polyethylene glycol 1000 succinate

d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, also known as vitamin E-TPGS) is a biodegradable amphiphilic polymer prepared by esterification of vitamin E with polyethylene glycol (PEG) 1000. It is approved by the US Food and Drug Administration (FDA) and has found wide application in nanocarrier drug delivery systems (NDDS). Fully characterizing the in vivo fate and pharmacokinetic behavior of TPGS is important to promote the further development of TPGS-based NDDS. However, to date, a bioassay for the simultaneous quantitation of TPGS and its metabolite, PEG1000, has not been reported. In the present study, we developed such an innovative bioassay and used it to investigate the pharmacokinetics, tissue distribution and excretion of TPGS and PEG1000 in rat after oral and intravenous dosing. In addition, we evaluated the interaction of TPGS with cytochromes P450 (CYP450s) in human liver microsomes. The results show that TPGS is poorly absorbed after oral administration with very low bioavailability and that, after intravenous administration, TPGS and PEG1000 are mainly distributed to the spleen, liver, lung and kidney before both being slowly eliminated in urine and feces as PEG1000. In vitro studies show the inhibition of human CYP450 enzymes by TPGS is limited to a weak inhibition of CYP3A4. Overall, our results provide a clear picture of the in vivo fate of TPGS which will be useful in evaluating the safety of TPGS-based NDDS in clinical use and in promoting their further development.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT).

Pharmacokinetic properties and in vitro enzyme activities of TPGS-modified arginine deiminase cyclodextrin lipid nanoparticles / 中国药理学通报

Aim To investigate the pharmacokinetic properties and in vitro enzyme activities of D-a-to- copherol polyethylene glycol 1000 succinate-modified arginine deiminase cyclodextrin lipid nanoparticles (ACLN). Methods The diacetylmonooxime-thiosem- icarbazide colorimetric method was used to determine the ADI enzyme activity, and the double reciprocal plot method was used to determine the enzyme Michae- lis constants. After the rats were given intravenously free ADI and ACLN, rat plasma samples were taken at different time points to determine the activity of ADI, and the time-enzyme activity curve would be drawn and the pharmacokinetic data analyzed by DAS 2. 1. 1. Re¬sults The optimum temperature for ADI and ACLN was 37 °C and the optimum pH was 6. 5. The Km val¬ ues of free ADI and ACLN were 0. 87 and 0. 74 mmol • L"1, respectively. The Vmai values of free ADI and ACLN were 53.28, 62.50 fjimol • L"' • min"1, re-spectively. The V

Carvedilol solid dispersion for enhanced oral bioavailability using rat model

The objective of the present study was to develop a solid dispersion formulation to improve oral bioavailability of poorly water-soluble drug carvedilol. Several solid dispersions were prepared by fusion-solvent method mixing different concentrations of Gelucire 44/14 and Gelucire 50/13. To the resultant solid dispersions, microcrystalline cellulose and amorphous fumed silica were added to obtain a free-flowing powder. The dissolution of carvedilol was evaluated using an USP Type-II dissolution apparatus. Solid dispersion with Gelucire 44/14 showed, in general, a lower extent of drug release when compared to Gelucire 50/13 at the same concentrations. Gelucire 50/13 in a ratio of 1 to 1.75 (drug: Gelucire) achieved a drug release of 83% in 4 hours, a 5-fold increase compared to pure carvedilol. When incorporating 10% D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS/ TPGS) a higher drug release was observed (88%). Parallel artificial membrane permeability assay was used to evaluate the in vitro diffusion. GelucireTPGS solid dispersion showed a higher permeability coefficient compared to pure drug. After oral administration to Sprague-Dawley rats, a significant increase in the oral bioavailability of carvedilol was observed when administered as a solid dispersion in combination with Gelucire-TPGS, 169% higher compared to pure drug suspension.

Study on Preparation and in vitro Release Characteristic of Ursolic Acid/PF 127/TPGS-doxorubicin Mixed Nanomicelles / 中国药房

OBJECTIVE： To prepare Ursolic acid （UA）/Pluronic F127 （PF127）/TPGS-doxorubicin （DOX） mixed nanomicelles， and to characterize it and study its in vitro release behavior. METHODS： UA/PF127/TPGS nanomicelles were prepared by thin film hydration method. Using encapsulation efficiency of UA as index， combined with the results of single factor tests， L9（34） orthogonal test was used to optimize drug dosage of UA， molar ratio of PF127 to TPGS， hydration temperature and hydration volume， validation test was performed. On the basis of succinylated TPGS， TPGS-DOX was synthesized and mixed with UA/PF127/TPGS to prepare UA/PF127/TPGS-DOX mixed nanomicelles， the appearance， particle size and critical micelle concentration （PF127/TPGS） were investigated. The drug release behavior was examined by dialysis bag diffusion method. RESULTS： The optimal preparation technology of UA/PF127/TPGS nanomicelles was as follows as drug dosage of UA 8 mg， molar ratio of PF127 to TPGS 3 ∶ 7， hydration temperature 50 ℃， hydration volume 4 mL. Average encapsulation efficiency of UA in nanomicelles was 89.00％ （RSD＝0.43％， n＝3）. The prepared UA/PF127/TPGS-DOX mixed nanomicelles solution was clear with opalescence. The nanomicelles were spherical and uniform in size； average particle size was （115.00±9.42） nm； critical micelle concentration of PF127/TPGS （molecular ratio 3 ∶ 7） was 0.001 3％. The in vitro drug release of UA and DOX in the mixed nanomicelles was significantly slowed down， compared with raw materials or substance control. The drug release process of the two drugs in the nanomicelles conformed to Weibull equation. CONCLUSIONS： UA/PF127/TPGS-DOX mixed nanomicelles are successfully prepared with uniform particle size， good stability and good sustained-release effect.

Lactobionic acid-decorated TPGS nanoparticles to decrease multidrug resistance on hepatocellular carcinoma / Монголын эм зүй, эм судлал

Introduction@#Many effective anticancer drugs are limited to use for hepatocellular carcinoma (HCC) therapy due to drug resistance mechanisms in liver cells. In recent years, tumor-targeted drug delivery and inhibition of drug resistance-related mechanisms become an integrated strategy to combat effectively chemoresistant cancer. @*Aim@#Herein, lactobionic acid-conjugated D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS-LA conjugate) was developed as a potential asialoglycoprotein receptor (ASG PR (-targeted nanocarrier and an efficient inhibitor of P-glycoprotein (P-gp) to enhance etoposide (ETO) efficacy against HCC. @*Methods@#Main properties of ETO-loaded TPGS-LA nanoparticles (NPs) were tested through in vitro and in vivo studies after prepared using nanoprecipitation method and characterized by dynamic light scattering (DLS). @*Results@#According to the results, smaller sized (~141.43 nm) and positively charged ETO-loaded TPGS-LA NPs were more suitable to provide an efficient delivery to hepatoma cells by avoiding clearance mechanisms. It was found that ETO-loaded TPGS-LA NPs could enhance noticeably cytotoxicity of ETO in HepG2 cells. Besides, markedly higher internalization by ASGPR overexpressed HepG2 cells and efficient accumulation at tumor site in vivo were revealed in TPGS-LA NPs group. More importantly, animal studies confirmed that ETO-loaded TPGS-LA NPs achieved the highest therapeutic efficacy against HCC. Interestingly, ETO-loaded TPGS-LA NPs also exhibited a great inhibitory effect on P-gp compared to ETO-loaded TPGS NPs. @*Conclusion@#These results suggest that TPGSLA NPs could be used as a potential delivery system of ETO against HCC.

Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations' physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (Cmax) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration-time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations' potential applications in drugs and healthcare products.

Enhanced water solubility, antioxidant activity, and oral absorption of hesperetin by D-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Hesperetin, an abundant bioactive component of citrus fruits, is poorly water-soluble, resulting in low oral bioavailability. We developed new formulations to improve the water solubility, antioxidant activity, and oral absorption of hesperetin. Two nano-based formulations were developed, namely hesperetin-TPGS (D-α-tocopheryl polyethylene glycol 1000 succinate) micelles and hesperetin-phosphatidylcholine (PC) complexes. These two formulations were prepared by a simple technique called solvent dispersion, using US Food and Drug Administration (FDA)-approved excipients for drugs. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) were used to characterize the formulations’ physical properties. Cytotoxicity analysis, cellular antioxidant activity assay, and a pharmacokinetic study were performed to evaluate the biological properties of these two formulations. The final weight ratios of both hesperetin to TPGS and hesperetin to PC were 1:12 based on their water solubility, which increased to 21.5- and 20.7-fold, respectively. The hesperetin-TPGS micelles had a small particle size of 26.19 nm, whereas the hesperetin-PC complexes exhibited a larger particle size of 219.15 nm. In addition, the cellular antioxidant activity assay indicated that both hesperetin-TPGS micelles and hesperetin-PC complexes increased the antioxidant activity of hesperetin to 4.2- and 3.9-fold, respectively. Importantly, the in vivo oral absorption study on rats indicated that the micelles and complexes significantly increased the peak plasma concentration (Cmax) from 2.64 μg/mL to 20.67 and 33.09 μg/mL and also increased the area under the concentration–time curve of hesperetin after oral administration to 16.2- and 18.0-fold, respectively. The micelles and complexes increased the solubility and remarkably improved the in vitro antioxidant activity and in vivo oral absorption of hesperetin, indicating these formulations’ potential applications in drugs and healthcare products.

Tissue distribution of TPGS modified artesunate liposome and its metabolites in rats / 中国中药杂志

Artesunate, which is a widely used anti-malaria medicine, can be made into liposome to overcome its poor bioactivity. Its tissue distribution in rats may change with different dosage forms, which therefore shall be studied after ARS-TPGS-Lipo was injected. Based on this experiment, ARS-TPGS-Lipo and ARS-Lipo were prepared by thin-film hydration method. LC-MS/MS method was used to simultaneously determine ARS and DHA in rat tissues at different time points. The results showed that this method was suitable for the content analysis of ARS and DHA in biological samples. The distribution of ARS and DHA in ARS-TPGS-Lipo, ARS-Lipo and ARS groups were quite different. The content of ARS-TPGS-Lipo in liver was the highest, with significant differences.ARS and DHA contents in ARS group eliminated rapidly. ARS and DHA contents in ARS-Lipo group were higher in liver and spleen, while those in ARS-TPGS-Lipo group significantly increased only in liver (<0.05).

Effect of curcumin-micelles adopting vitamin E-TPGS and Solutol HS 15 as carriers on solubility and oral bioavailability of curcumin / 中草药

Objective: To prepare curcumin-micelles adopting vitamin E-TPGS (VE-TPGS) and Solutol HS15 (SHS15) as carriers, and study the effect on solubility and oral bioavailability of curcumin (Cur). Methods: Cur was loaded into micelles between VE-TPGS and SHS15 by thin film dispersion method. Particle size, loading efficiency, entrapment efficiency, and in vitro release were carried on to estimate the influence of micelles on Cur; Moreover, oral bioavailability in rats was also evaluated. Results: The particle size was (35.79 ± 1.23) nm with polydispersity index (PDI) of 0.12 ± 0.03 when the optimized micelles ratio was at 3:7 of VE-TPGS and SHS15, which increased the solubility of Cur to 2.03 mg/mL in water. The entrapment efficiency and drug loading were 90.03% and 9.34%, respectively. The in vitro release profile showed a sustained release property compared with that of Cur. In addition, the relative bioavailability of micelles (AUC0~∞) compared with that of Cur (AUC0~∞) was 303.5% (P < 0.01). Conclusion: The Cur-micelles combined use of VE-TPGS and SHS15 shows great potential clinical application.

Investigation of the Liver-targeting Properties of Quercetin-loaded PLGA-TPGS Nanoparticles in HCa-F Cell-bearing Mice / 中国医科大学学报

Objective The aim of this study was to investigate the distribution and liver-targeting properties of quercetin (QT)/coumarin 6 (C6)-loaded polylactic-co-glycolic acid-D-α-tocopherol polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (QCPTN) in a hepatocarcinoma ectopic transplantation solid tumor model using HCa-F cell-bearing mice.Methods The QT concentrations in biological samples were determined using reverse phase-high performance liquid chromatography (RP-HPLC) analysis.After intravenous administration to mice in the QCPTN and QTS groups,the QT concentration in plasma and in different tissues was simultaneously analyzed at the different time points.Detection indexes (relative targeting efficiency,Re;targeting efficiency,Te) and fluorescence inversion microscopy images of the frozen tissue (liver,solid tumor,spleen,lungs,kidneys,and heart) slices were used for quantitatively and qualitatively evaluating the liver-targeting properties of QCPTN in solid tumor-bearing mice.Results Te of the QCPTN group in the plasma,liver,solid tumor,spleen,lungs,kidneys,and heart were all greater than 3,indicating that the area under the concentration-time curve (AUC) of liver was more than three times that of the plasma and other organs.Fluorescence inversion microscopy images showed that the green fluorescence of QCPTN was mostly observed in the liver.Conclusion Using HCa-F cell-beating mice,QCPTN was found to have better in vivo liver-targeting properties in hepatocarcinoma ectopic transplantation solid tumor.

Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles as oral drug carrier for lung cancer chemotherapy / 国际生物医学工程杂志

Objective To construct a novel thiolated chitosan modified poly(lactide-co-ε-caprolactone)-d-α-tocopheryl polyethylene glycol 1 000 succinate (PLA-PCL-TPGS) nanoparticle,and investigate the feasibility of its use as an oral carrier for lung cancer chemotherapy.Methods The PLA-PCL-TPGS random copolymer was synthesized and characterized.Then three types of nanoparticles from commercial PCL and PLA-PCL-TPGS random copolymer were prepared for oral carrier of paclitaxel,including 5％ thiolated chitosan-modified PCL nanoparticles (CNPs),unmodified PLA-PCL-TPGS nanoparticles (UNPs),and 5％ thiolated chitosan-modified PLA-PCL-TPGS nanoparticles (TNPs).The prepared nanoparticles were characterized in terms of size,Zeta potential,morphology,drug loading and encapsulation efficiency.The in vitro drug release profiles and cellular uptake of the nanoparticles by human lung cancer cell lines A549 cells were investigated,and cytotoxicity against A549 cells was also evaluated.The evened sac method was used for the measurement of transportation of paclitaxel across the intestine barrier.Results The field emission scanning electron microscopy results showed that the three types of paclitaxel-loaded nanoparticles were spherical with a diameter about 200 nm.The surface charge of PLA-PCL-TPGS nanoparticles was reversed from negative to positive charge after thiolated chitosan modification.The UNPs and TNPs achieved higher drug loading,encapsulation efficiency and drug release after 32 d than CNP (all P＜0.05).The TNPs had significantly higher cell uptake efficiency than that of CNPs and UNPs (all P＜0.05).In vitro cell viability studies showed advantages of TNPs over a clinically available paclitaxel injection in terms of cytotoxicity against A549 cells.Ex vivo absorption studies revealed that the TNPs can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein.Conclusion PLA-PCL-TPGS nanoparticles modified by thiolated chitosan can enhance the cellular uptake and cytotoxicity,which reveals a potential application for oral chemotherapy of lung cancer.

Preparation of TPGS-modified artesunate liposomes and their in vitro anti-tumor activity / 中成药

AIM To prepare D-α-tocopherol polyethylene glycol 1000 succinate (TPGS)-modified artesunate liposomes and to investigate the in vitro anti-tumor activity.METHODS The liposomes prepared by thin-film dispersion method were characterized by transmission electron microscopy and particle size analyzer,and the encapsulation efficiency was determined by ultrafiltration centrifugation.The liposomes' cytotoxicity to human hepatoma HepG2 cells was evaluated by MTT method.RESULTS The average particle size,PDI,Zeta potential,encapsulation efficiency,drug loading of the liposomes were 126.7 nm,0.182,-10.1 mV,78.8％ and 18.38％,respectively.The liposomes displayed a significant inhibition on HepG2 cells with the IC50 value of 0.034 μmol/mL.CONCLUSION Compared with non-TPGS-modified artesunate liposomes,the TPGS-modified artesunate liposomes prepared by this method afford smaller vesicle size,better stability and higher encapsulation efficiency with stronger in vitro anti-tumor activity.

Liquid crystalline systems containing Vitamin E TPGS for the controlled transdermal nicotine delivery

ABSTRACT Transdermal nicotine patches have been used in smoking cessation therapy, suggested for the treatment of skin disorders with eosinophilic infiltration and have been found to improve attention performance in patients with Alzheimer's disease and age-associated memory impairment. However, skin irritation with extended patch use is still a problem. The aim of this work was to develop a simple to prepare liquid crystalline system containing vitamin E TPGS that would be able to control nicotine delivery and reduce irritation and sensitization problems. The liquid crystalline phases were macroscopically characterized by visual analysis and examined microscopically under a polarized light microscope. Topical and transdermal delivery of nicotine were investigated in vitro using porcine ear skin mounted on a Franz diffusion cell. Nicotine skin permeation from the developed cubic phase followed zero-order kinetics (r = 0.993) and was significantly enhanced after 12 h when compared to the control formulation (nicotine solution) (p < 0.05) (138.86 ± 20.44 and 64.91 ± 4.06 μg/cm2, respectively). Cubic phase was also able to target viable skin layers in comparison to control solution (8.18 ± 1.89 and 2.63 ± 2.51 μg/cm2, respectively). Further studies to evaluate skin sensitization and irritation are now necessary.

RESUMO Adesivos transdérmicos de nicotina são utilizados para cessação de fumar, tratamento de problemas de pele com infiltração de eosinófilos e para melhorar a atenção em pacientes com doença de Alzheimer e enfraquecimento da memória associada à idade. No entanto, a irritação da pele com o uso prolongado dos adesivos ainda é um problema. O objetivo deste trabalho foi desenvolver sistema líquido cristalino (SLC) de preparo simples contendo vitamina E TPGS capaz de controlar a liberação de nicotina e reduzir os problemas de irritação cutânea. Os SLCs foram caracterizados por análise visual e microscopia de luz polarizada. As administrações tópica e transdérmica de nicotina foram investigadas in vitro utilizando pele de orelha de porco em célula de difusão de Franz. A permeação da nicotina veiculada pela fase cúbica desenvolvida seguiu cinética de ordem zero (r = 0,993) e foi significativamente maior do que o controle (solução de nicotina) após 12 h (p < 0,05) (138,86 ± 20,44 e 64,91 ± 4,06 µg/cm2, respectivamente). A fase cúbica também promoveu aumento da penetração de nicotina nas camadas viáveis da pele quando comparado ao controle (8,18 ± 1,89 e 2,63 ± 2,51 µg/cm2, respectivamente). Estudos futuros para avaliar a sensibilização e irritação da pele são necessários.

Preparation and in vitro evaluation of ampelopsin-loaded nanomicelles / 中国中药杂志

To improve the solubility and antitumor activity of ampelopsin, ampelopsin-loaded nanomicelles from the mixture of pluronic F127 and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) were prepared by film-thin hydration method, in order to optimize the process conditions and physicochemical properties. The antitumor activities against MCF-7 cells between ampelopsin and nanomicelles were compared by MTT method, respectively. The results showed that the optimal nanomicelles were round with the nanometric size of (22.6±0.5) nm, encapsulation efficiency rate of (80.42±1.13)%, and drug-loading rate of (4.41±0.26)%. The solubility of ampelopsin in mixed nanomicelles significantly increased by 16 times. In different release media, the mixed nanomicelles could release more than 90% of drug in 8 h, and showed stronger cytotoxicity and inhibition against MCF-7 cells (P<0.01). The mixed nanomicelles can be used as new drug delivery system of ampelopsin.

Influence of TPGS 1000 and Soluplus on membrane transport of ginsenoside CK in Caco-2 cell monolayer model / 中国药学杂志

OBJECTIVE: To examine the effects of TPGS 1000 and Soluplus on the transport of ginsenoside CK in Caco-2 cell model. METHODS: The effects of TPGS 1000 and Soluplus at different concentrations on ginsenoside CK were evaluated by using Caco-2 cell model. The concentration of ginsenoside CK in cell was examined by ultra high pressure liquid chromatography (UPLC) method. The apparent permeability coefficient (Papp) and the efflux ratio were calculated. RESULTS: When the proportion of ginsenoside CK to TPGS 1000 or Soluplus was 1:1, 1:3, and 1:9, the absorption of ginsenoside CK significantly increased. The efflux and efflux ratio both decreased significantly (P<0.05). TPGS 1000 had more significant promotion effect on the transport of ginsenoside CK than the same dose of soluplus at the same ratio (P<0.05). CONCLUSION: In Caco-2 cell model, both TPGS 1000 and Soluplus can significantly promote the absorption of ginsenoside CK.

Preparation and characterization of baicalin-loaded polymeric micelles and its inhibition on MCF-7 cells / 中草药

Objective: To prepare baicalin-loaded TPGS nanomicells (BCN-TPGS-PMs) and to evaluate its physicochemical properties, in vitro release behavior, and antitumor activity against MCF-7 cells. Methods: BCN-TPGS-PMs were prepared by film-thin hydration method. The preparation methods and formulations were optimized and screened based on particle size and encapsulation efficiency (EE) of micelles. The transmission electron microscope (TEM) was used to observe the particle appearance, zetasizer instrument was used to detect the diameter and Zeta potential, and ultracentrifugation was utilized to determine the EE and drug-loading rate. Dynamic dialysis method was used to study the in vitro release behavior of BCN-TPGS-PMs, and the antitumor activity against MCF-7 cells was determined by MTT method. Results: The optimal BCN-TPGS-PMs were round with the nanometric size of (11.91 ± 0.14) nm, high EE rate of (95.83 ± 7.34)%, and drug-loading rate of (5.42 ± 0.04)%. The in vitro release behavior showed that BCN-TPGS-PMs had a slow release. Compared with free BCN, BCN-TPGS-PMs showed stronger cytotoxicity and inhibition against MCF-7 cells (P < 0.05). Conclusion: The prepared BCN-TPGS-PMs have small particle size, high drug-loading rate, and good stability, and could obviously increase the in vitro inhibitory effect of BCN.

Preparation of colchicine ethosomes containing TPGS and in vitro transdermal permeation / 中草药

Objective: To prepare and optimize the prescription of colchicine ethosomes containing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and to investigate its feasibility as a carrier for transdermal drug delivery. Methods: The colchicine ethosomes containing TPGS were prepared by the injection-sonication method. And the encapsulation efficiency (EE) was determined by minicolumn centrifugation method. The prescription of ethosomes was optimized by uniform design with EE as the evaluation index, and the physicochemical properties of the optimized ethosomes were investigated. Characterization of the vesicles was based on particle size, Zeta potential, entrapment efficiency, and transmission electron microscopy (TEM). The transdermal permeation characteristics of ethosomes, colchicine 30% ethanol solution, and colchicine ethosomes containing TPGS were compared by using Franz diffusion cells. Results: The optimized formulation was as follows: The contents of soybean phospholipid and TPGS were 350 and 50 mg, respectively. In addition, the concentration of ethanol was 36.44%. The average EE, particle size, polydispersity index, and Zeta potential were (74.71 ± 2.18)%, (89.6 ± 3.5) nm, 0.201 ± 0.008, and (-34.6 ± 2.7) mV, respectively. The in vitro experiment showed that the transdermal flux, permeation rate, and skin deposition of colchicine ethosomes were (64.49 ± 5.61) μg/cm2, (2.84 ± 0.23) μg/(cm2∙h), (128.22 ± 11.64) μg/cm2, and the transdermal flux, permeation rate, and skin deposition of colchicine ethosomes containing TPGS were (91.36 ± 7.11) μg/cm2, (4.73 ± 0.38) μg/(cm2∙h), and (182.84 ± 14.37) μg/cm2, respectively, which was significantly higher than those in ethosomes. Conclusion: The colchicine ethosomes containing TPGS show high EE and obviously enhance the percutaneous absorption of colchicine, which might be a potential carrier for transdermal drug delivery.

Advance in application of D-α-tocopherol polyethyleneglycol succinate in the field of pharmaceutics / 中国药学杂志

OBJECTIVE: To review the applications of D-α-tocopherol polyethylene glycol succinate (TPGS) as a drug carrier in pharmaceutical preparation.

Preparation of paclitaxel-loaded mixed micelles and its in situ absorption in rat intestine / 中国药学杂志

OBJECTIVE: To study the oral absorption of paclitaxel-loaded mixed micelles made of D-α-tocopherol polyethylene glycol 1000 succinate(TPGS) and sodium cholate(NaC) in rats. METHODS: Paclitaxel-loaded mixed micelles were prepared by film dispersion method. The Zeta potential and diameter distribution of TPGS/NaC mixed micelles were measured using laser size scattering determinator. The morphology of micelles was observed by transmission electron microscope. Dialysis method was used to evaluate the release behavior of drug-loaded micelles in vitro. The absorption kinetics was obtained by in situ perfusion method in rats. RESULTS: Most of the mixed micelles were spherical with an average diameter of 24.2 nm and the Zeta potential was -7.84 mV. Compared to the bulk drug, the apparent absorption rate constant (Ka)of paclitaxel-loaded mixed micelles was increased significantly. CONCLUSION: TPGS/NaC mixed micelles can improve the oral absorption of paclitaxel and increase its oral bioavailability.