A ceramic-based anticancer drug delivery system to treat breast cancer

Drug delivery systems offer the advantage of sustained targeted release with minimal side effect. In the present study, the therapeutic efficacy of a porous silica–calcium phosphate nanocomposite (SCPC) as a new delivery system for 5-Fluorouracil (5-FU) was evaluated in vitro and in vivo. In vitro studies showed that two formulations; SCPC50/5-FU and SCPC75/5-FU hybrids were very cytotoxic for 4T1 mammary tumor cells. In contrast, control SCPCs without drug did not show any measurable toxic effect. Release kinetics studies showed that SCPC75/5-FU hybrid provided a burst release of 5-FU in the first 24 h followed by a sustained release of a therapeutic dose (30.7 μg/day) of the drug for up to 32 days. Moreover, subcutaneous implantation of SCPC75/5-FU hybrid disk in an immunocompetent murine model of breast cancer stopped 4T1 tumor growth. Blood analyses showed comparable concentrations of Ca, P and Si in animals implanted with or without SCPC75 disks. These results strongly suggest that SCPC/5-FU hybrids can provide an effective treatment for solid tumors with minimal side effects.     

Gold nanoparticles capped with benzalkonium chloride and poly (ethylene imine) for enhanced loading and skin permeability of 5-fluorouracil

Objective: To enhance 5-fluorouracil (5-FU) permeability through the skin by loading onto gold nanoparticles (GNPs) capped with two cationic ligands, benzalkonium chloride (BC) or poly (ethylene imine) (PEI). Whereas 5-FU has excellent efficacy against many cancers, its poor permeability through biological membranes and several adverse effects limit its clinical benefits. BC and PEI were selected to stabilize GNPs and to load 5-FU through ionic interactions.

Methods: 5-FU/BC-GNPs and 5-FU/PEI-GNPs were prepared at different 5-FU/ligand molar ratios and different pH values and were evaluated using different techniques. GNPs stability was tested as a function of salt concentration and storage time. 5-FU release from BC- and PEI-GNPs was evaluated as a function of solution pH. Ex vivo permeability studies of different 5-FU preparations were carried out using mice skin.

Results: 5-FU-loaded GNPs size and surface charge were dependent on the 5-FU/ligand molar ratios. 5-FU entrapment efficiency and loading capacity were dependent on the used ligand, 5-FU/ligand molar ratio and solution pH. Maximum drug entrapment efficiency of 59.0?±?1.7% and 46.0?±?1.1% were obtained for 5-FU/BC-GNPs and 5-FU/PEI-GNPs, respectively. 5-FU-loaded GNPs had good stability against salinity and after storage for 4?months at room temperature and at 4?°C. In vitro 5-FU release was pH- and ligand-dependent where slower release was observed at higher pH and for 5-FU/BC-GNPs. 5-FU permeability through mice skin was significantly higher for drug-loaded GNPs compared with drug-ligand complex or drug aqueous solution.

Conclusion: Based on these results, BC- and PEI-GNPs might find applications as effective topical delivery systems of 5-FU.     

Preparation of ethosomes and deformable liposomes encapsulated with 5-fluorouracil and their investigation of permeability and retention in hypertrophic scar

With the aim of comparing scar penetration efficiency and retention between ethosomes and deformable liposomes both encapsulated with 5-fluorouracil (5-FU), the 5-FU ethosomal suspensions (5-FU ES, 81.74 +/- 9.37 nm) and the 5-FU Deformable Liposomal Suspensions (5-FU DS, 73.7 +/- 9.45 nm) were prepared respectively by Touitou method and Cevc method, their sizes were determined by Particle Sizer System (PSS), and their entrapment Efficiency (EE) was detected by ultracentrifugation and microcolumn centrifugation. Their transdermal delivery experiments were done in hypertrophic scars in vitro. The permeated amount of 5-FU and retention contents of 5-FU were both calculated by High Performance Liquid Chromatography (HPLC). Fluorescence intensities of ES and DS labeled with Rodanmin 6GO (Rho) were measured by Laser Scanning Microscopy (LSM). The control groups such as the 5-FU and empty ethosomal vesicles (5-FU + EEV), the 5-FU and empty deformable liposomal vesicles (5-FU + EDV) and 5-FU PBS Solution (5-FU Sol) were set up. Results showed that, prepared 5-FU ES was 81.74 +/- 9.37 nm in size, 5-FU DS was 73.7 +/- 9.45 nm, EE of 5-FU ES was 10.95%, EE of 5-FU DS was 15.05%. Within 24 hours, in the group of 5-FU ES, the penetration amount of 5-FU in scar was 14.12 +/- 0.1 microg/mL/cm2, the retention contents of 5-FU was 10.74 +/- 1.17 microg/cm2, and the fluorescence intensity of Rho in hypertrophic scar tissues were 182 +/- 18.3; in the group of 5-FU DS: the penetration amount of 5-FU was 12.35 +/- 1.21 microg/mLcm2; the retention contents of 5-FU was 17.48 +/- 0.82 microg/cm2, and the fluorescence intensity of Rho was 241.45 +/- 7.63; there existed statistical difference between penetration amount in the group of 5-FU ES and that in the group of 5-FU DS as well as control groups (P < 0.05, P < 0.01), the penetration amount in the group of ES is markedly higher than DS group or control groups. Conversely, the retention contents of 5-FU and the fluorescence intensity of Rho in DS group were higher than those in ES group and control groups (P < 0.05, P < 0.01). In conclusion, both ES and DS could deliver 5-FU into the hypertrophic scars effectively. ES has better permeability of 5-FU than DS, DS has higher entrapment efficiency of 5-FU, and more 5-FU deposition in hypertrophic scar than ES. We should select ES or DS encapsulated with 5-FU according to clinical demand for hypertrophic scar therapy.     

PLGA nanoparticles for the oral delivery of 5-Fluorouracil using high pressure homogenization-emulsification as the preparation method and in vitro/in vivo studies

The objective of the present study was to incorporate the hydrophilic anti-cancer drug 5-Fluorouracil(5-FU) into poly(lactide-co-glycolide) (PLGA) nanoparticles(NP) to improve the oral bioavailability. Owing to the high solubility of 5-FU in basic water, the water-in-oil-in-water (w/o/w) emulsification process has been chosen as one of the most appropriate method for the encapsulation of 5-FU, and the ammonia solution was used as the inner aqueous phase solvent to increase the solubility of 5-FU. In order to reach submicron size as well as increasing the grade of monodispersity compared to previous preparation techniques, we prepared 5-FU loaded PLGA-NP by a high-pressure emulsification-solvent evaporation process. The PLGA-NPs were characterized with respect to their morphology, particle size, size distribution, 5-FU encapsulation efficiency, in vitro and in vivo studies in rats. In vitro release of 5-FU from nanoparticles appeared to have two components with an initial rapid release due to the surface associated drug and followed by a slower exponential release of 5-FU, which was dissolved in the core. The in vivo research was studied in male Sprague-Dawley rats after an oral 5-FU dose of 45 mg/kg. Single oral administration of 5-FU loaded PLGA-NP to rats produced bioavailability, which was statistically higher than 5-FU solution as negative control. And the MRT (mean residence time) of 5-FU loaded PLGA-NP was significantly (P < 0.05) modified. Thus, it is possible to design a controlled drug delivery system for oral 5-FU delivery, improving therapy efficiency by possible reduction of time intervals between peroral administrations and reduction of local gastrointestinal side effects.     

聚天冬氨酸交联温敏性水凝胶的药物缓释性能

选用牛血清蛋白(BSA)和5-氟尿嘧啶(5-FU)为模型药物,以聚天冬氨酸交联温敏性水凝胶为载体材料,采用包埋法制备了载药水凝胶,研究了水凝胶的载药和释药性能。水凝胶对BSA和5-FU的包埋率均大于98%。37℃时,水凝胶中丙烯酸用量越大,BSA的释放率越低;交联剂用量对BSA的释放率无显著影响。25℃时,丙烯酸用量越大,5-FU的释放率越大;交联剂用量越大,5-FU的释放率越小。37℃时,丙烯酸用量越小,5-FU的释放率越大;交联剂用量越大,5-FU的释放率越小。     

Microprocessor in controlled transdermal drug delivery of anti-cancer drugs

Microprocessor controlled transdermal delivery of anticancer drugs 5-Fluorouracil (5-FU) and 6-Mercaptopurine (6-MP) was developed and in vitro evaluation was done. Drugs were loaded based on the pharmacokinetics parameters. In vitro diffusion studies were carried at different current density (0.0, 0.1, 0.22, 0.50 mA/cm2). The patches were evaluated for the drug content, thickness, weight, folding endurance, flatness, thumb tack test and adhesive properties all were well with in the specification of transdermal patches with elegant and transparent in appearance. In vitro permeation studies through human cadaver skin showed, passive delivery (0.0 mA/cm2) of 6-MP was low. As the current density was progressively increased, the flux also increased. the flux also increased with 0.1 mA/cm2 for 15-20 min, but it was less than desired flux, 0.2 mA/cm2 for 30 min showed better flux than 0.1 mA/cm2 current, but lag time was more than 4 h, 0.5 mA/cm2 current for more than 1 h, flux was >159 microg/cm2 h which was desired flux for 6-MP. 5-FU flux reached the minimum effective concentration (MEC) of 54 microg/cm2 h with 0.5 mA/cm2 current for 30-45 min, drug concentration were within the therapeutic window in post-current phase. We concluded from Ohm's Law that as the resistance decreases, current increases. Skin resistance decrease with increase in time and current, increase in the drug permeation. Interestingly, for all investigated current densities, as soon as the current was switched off, 5-FU and 6-MP flux decreased fairly, but the controlled drug delivery can be achieved by switching the current for required period of time.     

Development and evaluation of novel microemulsion based oral formulations of 5-fluorouracil using non-everted rat intestine sac model

Oral formulations of 5-fluorouracil (5-FU) with enhanced bioavailability were developed using microemulsion as a drug carrier system. The formulations were evaluated for drug content, physicochemical characteristics such as globule size, zeta potential, viscosity, stability and permeation characteristics. Ex vivo permeation studies were performed using non-everted rat intestinal sac technique. Results of the ex vivo permeation studies revealed that from aqueous solution only 25.08% drug was permeated, whereas, the optimized microemulsion formulation showed 97.5% drug permeation in 8?h, suggesting, approximately, four times enhancement in the drug permeability. Also a 7-fold increase in the flux of drug was observed from microemulsion formulation when compared with the aqueous solution. Further, in vivo pharmacodynamic studies were carried to check the therapeutic efficacy against benzo(a)pyrene [B(a)P]-induced stomach tumors in albino mice (Balb/C strain). The treatment of mice with 5-FU and microemulsion (5-FU II), after the last dose of B(a)P i.e. during the initiation period, resulted in 25% and 67% reduction in tumor incidence, respectively suggesting significant enhancement in the bioavailability and therapeutic efficacy of 5-FU when it was formulated as a microemulsion. These promising results suggest that microemulsion formulation of 5-FU may be used for the treatment of human cancers after pharmacokinetic and clinical evaluation.     

Development and evaluation of novel microemulsion based oral formulations of 5-fluorouracil using non-everted rat intestine sac model

Oral formulations of 5-fluorouracil (5-FU) with enhanced bioavailability were developed using microemulsion as a drug carrier system. The formulations were evaluated for drug content, physicochemical characteristics such as globule size, zeta potential, viscosity, stability and permeation characteristics. Ex vivo permeation studies were performed using non-everted rat intestinal sac technique. Results of the ex vivo permeation studies revealed that from aqueous solution only 25.08% drug was permeated, whereas, the optimized microemulsion formulation showed 97.5% drug permeation in 8?h, suggesting, approximately, four times enhancement in the drug permeability. Also a 7-fold increase in the flux of drug was observed from microemulsion formulation when compared with the aqueous solution. Further, in vivo pharmacodynamic studies were carried to check the therapeutic efficacy against benzo(a)pyrene [B(a)P]-induced stomach tumors in albino mice (Balb/C strain). The treatment of mice with 5-FU and microemulsion (5-FU II), after the last dose of B(a)P i.e. during the initiation period, resulted in 25% and 67% reduction in tumor incidence, respectively suggesting significant enhancement in the bioavailability and therapeutic efficacy of 5-FU when it was formulated as a microemulsion. These promising results suggest that microemulsion formulation of 5-FU may be used for the treatment of human cancers after pharmacokinetic and clinical evaluation.     

1-Alkylcarbonyl-5-fluorouracil Prodrugs: Synthesis,Thermal and Hydrolytic Stability

Abstract

Six homologous 1 -alkylcarbonyl derivatives of 5-fluorouracil (5-FU) have been synthesized and characterized by ¹H NMR, infrared and UV spectroscopy. The derivatives were found to hydrolyze rapidly in pH 7.1 buffer at 32°C (t_1/2 = 3-5 min). Although the hydrolysis was found to be catalyzed by hydrated formaldehyde, only 5-FU was observed as a product of the hydrolysis: no 1- or 3-alkylcarbonyloxymethyl products were observed. The 1 -alkylcarbonyl derivatives were recovered intact upon heating at 145°C for 1 h, but, upon heating at 205°C for 1 h, 25% of the sample decomposed to 5-FU with the assumed loss of ketene. The 1-alkylcarbonyl derivatives were stable when stored in a desiccator but decomposed to carboxylic acid and 5-FU upon exposure to atmospheric moisture.     

Preparation and characterization of different sizes of ethosomes encapsulated with 5-fluorouracil and its experimental study of permeability in hypertrophic scar

With the aim of investigating scar penetration efficiency of different sizes of ethosomes encapsulated with Fluorouracil, three kinds of ethosomes with different sizes were prepared by extruding the vesicles through polycarbonate membrane filters, their encapsulation efficiency of Fluorouracil (5-FU) were investigated by dialysis method, their scar-penetration efficiencies were analyzed by filling Rodanmin 6GO into ethosomes and using confocal laser scanning microscopy (CLSM). The prepared ethosomes were 216 +/- 19 nm, 107 +/- 13 nm, and 65 +/- 10 nm in diameter respectively, and exhibited good dispersibility. Their encapsulation efficiency of 5-FU were 12%, 34%, and 41%, respectively. The results indicated that the 5-FU penetration was reversely related to the size of the size of the ethosomes. The ethosomes of 65 nm in diameter exhibited maximal fluorescence penetration efficiency which could reach the deep layer of dermis of hypertrophic scar. In conclusion, three different sizes of 5-FU ethosomes were prepared successfully, the ethosomes of 65 nm in diameter with 5-FU can penetrate scar high efficiently, which has potential in application such as anti-scar drug carriers in scar therapy in near future.     

5-Fluorouracil-loaded PLA/PLGA PEG–PPG–PEG polymeric nanoparticles: formulation,in vitro characterization and cell culture studies

In this study, 5-FU, a potent anticancer drug, is planned to be delivered via a new and promising drug delivery system, nanoparticles formed with hydrophobic core polymer and triblock copolymers; Poly(DL-lactic acid), Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLA/PEG-PPG-PEG) and Poly(D,L-lactide–co-glycolide)/Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) copolymer (PLGA/PEG-PPG-PEG) nanoparticles. Particle size range of nanoparticles was found to be between 145 and 198?nm, which would promote the passive targeting of the nanoparticles to tumor cells based on the enhanced permeability and retention (EPR) effect. SEM images revealed all nanoparticles formulations to be spherical and without pores. Zeta potential, yield value and encapsulation efficiencies of 5-FU-loaded nanoparticles were within the range of ?11.1 and ?13.7?mV, 72.7–87.7% and 83.6–93.9%, respectively. Cumulative release of 5-FU was observed between 90% and 94.4% in all nanoparticle formulations by the end of 72?h, and fitness of release profiles to Higuchi model indicated matrix-controlled diffusion of the 5-FU from polymeric nanoparticles. Cell viability values of the cells treated with 5-FU-loaded nanoparticles were obtained as low as 47% and 52% with tetrazolium dye assay, suggesting that delivery of 5-FU via amphiphilic triblock copolymer nanoparticles would be a promising delivery system because of the EPR effect.     

Preparation and characterization of chitosan hydrogel membrane for the permeation of 5-Fluorouracil

Four kinds of chitosan membranes, (Ch, C-G, C-N, and C-GN), were prepared in this study. Ch system of chitosan membranes were prepared by solution casting method without any treatment. C-G system of chitosan membranes were prepared by solution casting method with adding glutaraldehyde as crosslinking agent. C-N system of chitosan membranes were prepared by solution casting method with the treatment of NaOH solution. C-GN system of chitosan membranes were crosslinked with glutaraldehyde and treated with 1 M NaOH solution. Infrared spectroscopy and differential scanning calorimetry (DSC) were conducted to characterize the structure and thermal properties of chitosan membrane. To evaluate the usage of chitosan for the carrier of drug, water content and degradation of the chitosan membrane were determined. It was found that the values of equilibrated water content in chitosan membranes increased with the chitosan content in the stock chitosan solution. The assessment of 5-FU permeability through the chitosan membranes was determined. The linear relationship between the permeability of 5-FU through the membrane and the wt.% of chitosan content in stock chitosan solution was found. Both values of intercept and slope were determined. The value of intercept means that the permeability of 5-FU through the chitosan membrane, which is assumed to be prepared from stock chitosan solution containing infinite dilute chitosan content. The value of slope indicates that the effect of the treatment method on the permeability of 5-FU through the chitosan membrane. From the evaluation of normalized flux, diffusivity and saturation concentration of 5-FU in various chitosan membrane, it was found that more number of 5-FU molecules were trapped in the chitosan membrane of C-GN system than that in C-N system and resulted in the decrease of diffusivity of 5-FU molecules through the chitosan membrane.     

Study on hydrophilic 5-fluorouracil release from hydrophobic poly(ϵ-caprolactone) cylindrical implants

Hydrophilic 5-fluorouracil (5-FU) loaded cylindrical poly(?-caprolactone) (PCL) implants with different implant diameters (2, 4 and 8?mm), different drug loadings (25% and 50%) and end-capping were fabricated and characterized. The implant structure, drug content and molecular weight of PCL after 120 days drug release were investigated. The in vitro release results showed that, when the drug loading was the same, drug release was fastest for the implant with a diameter of 2?mm and slowest for the implant with a diameter of 8?mm; for the implants with the same diameters, the release of drug from the implants with 50% drug loading was faster than that from the implants with 25% drug loading; however, this effect of drug loading decreased with the increase of implant diameter; in addition, 5-FU was released slightly slower from the end-capped implants than from the corresponding uncapped implants; the drug release data for all the uncapped implants were best fit with the Ritger-Peppas model. Drug release from the hydrophobic implants was found to be dominated by diffusion mechanism. Scanning electron microscopy images and drug content measurements revealed that 5-FU release took place gradually from the exterior region to the interior region of the implants.     

Study on hydrophilic 5-fluorouracil release from hydrophobic poly(ε-caprolactone) cylindrical implants

Hydrophilic 5-fluorouracil (5-FU) loaded cylindrical poly(ε-caprolactone) (PCL) implants with different implant diameters (2, 4 and 8 mm), different drug loadings (25% and 50%) and end-capping were fabricated and characterized. The implant structure, drug content and molecular weight of PCL after 120 days drug release were investigated. The in vitro release results showed that, when the drug loading was the same, drug release was fastest for the implant with a diameter of 2 mm and slowest for the implant with a diameter of 8 mm; for the implants with the same diameters, the release of drug from the implants with 50% drug loading was faster than that from the implants with 25% drug loading; however, this effect of drug loading decreased with the increase of implant diameter; in addition, 5-FU was released slightly slower from the end-capped implants than from the corresponding uncapped implants; the drug release data for all the uncapped implants were best fit with the Ritger-Peppas model. Drug release from the hydrophobic implants was found to be dominated by diffusion mechanism. Scanning electron microscopy images and drug content measurements revealed that 5-FU release took place gradually from the exterior region to the interior region of the implants.     

Calcium pectinate capsules for colon-specific drug delivery

The calcium pectinate (CaP) capsule, a novel, colon-specific delivery system, was designed and developed using 5-fluorouracil (5-FU) as a model drug. Technically, CaP capsules were prepared by dipping a glass or stainless steel rod successively into pectin and calcium chloride solutions, followed by subsequent air-drying and coating. In vitro studies showed that the release of 5-FU from CaP capsules markedly increased in the presence of rat cecal contents, and the release characteristic was mainly associated with some capsule parameters such as calcium content, shell thickness, and coat amount. Gamma scintigraphic studies demonstrated that CaP capsules could pass through the stomach and small intestine intact and could release drug in colon. The 5-FU releasing characteristics acquired both from in vitro biomimic dissolution experiments and from healthy volunteers indicated that the newly developed CaP capsule possessed the ideal colon-specific drug delivery characteristic.     

Calcium Pectinate Capsules for Colon-Specific Drug Delivery

The calcium pectinate (CaP) capsule, a novel, colon-specific delivery system, was designed and developed using 5-fluorouracil (5-FU) as a model drug. Technically, CaP capsules were prepared by dipping a glass or stainless steel rod successively into pectin and calcium chloride solutions, followed by subsequent air-drying and coating. In vitro studies showed that the release of 5-FU from CaP capsules markedly increased in the presence of rat cecal contents, and the release characteristic was mainly associated with some capsule parameters such as calcium content, shell thickness, and coat amount. Gamma scintigraphic studies demonstrated that CaP capsules could pass through the stomach and small intestine intact and could release drug in colon. The 5-FU releasing characteristics acquired both from in vitro biomimic dissolution experiments and from healthy volunteers indicated that the newly developed CaP capsule possessed the ideal colon-specific drug delivery characteristic.     

Microprocessor in controlled transdermal drug delivery of anti-cancer drugs

Microprocessor controlled transdermal delivery of anticancer drugs 5-Fluorouracil (5-FU) and 6-Mercaptopurine (6-MP) was developed and in vitro evaluation was done. Drugs were loaded based on the pharmacokinetics parameters. In vitro diffusion studies were carried at different current density (0.0, 0.1, 0.22, 0.50 mA/cm²). The patches were evaluated for the drug content, thickness, weight, folding endurance, flatness, thumb tack test and adhesive properties all were well with in the specification of transdermal patches with elegant and transparent in appearance. In vitro permeation studies through human cadaver skin showed, passive delivery (0.0 mA/cm²) of 6-MP was low. As the current density was progressively increased, the flux also increased. the flux also increased with 0.1 mA/cm² for 15–20 min, but it was less than desired flux, 0.2 mA/cm² for 30 min showed better flux than 0.1 mA/cm² current, but lag time was more than 4 h, 0.5 mA/cm² current for more than 1 h, flux was >159 µg/cm² h which was desired flux for 6-MP. 5-FU flux reached the minimum effective concentration (MEC) of 54 μg/cm² h with 0.5 mA/cm² current for 30–45 min, drug concentration were within the therapeutic window in post-current phase. We concluded from Ohm’s Law that as the resistance decreases, current increases. Skin resistance decrease with increase in time and current, increase in the drug permeation. Interestingly, for all investigated current densities, as soon as the current was switched off, 5-FU and 6-MP flux decreased fairly, but the controlled drug delivery can be achieved by switching the current for required period of time.     

在交联聚乙烯醇微球表面接枝聚合甲基丙烯酸及接枝微球对含氮代谢及药物分子吸附特性的初探

交联聚乙烯醇(CPVA)微球是一种生物相容性聚合物微球,利用其表面大量的羟基,与铈盐构成氧化还原引发体系,实现了甲基丙烯酸(MAA)的表面引发接枝聚合,制备了接枝微球CPVA-g-PMAA.采用红外光谱(FT-IR)法、扫描电子显微镜(SEM)及zeta电位测定等法,对接枝微球的化学结构及物理化学特性进行了表征.初步考察了接枝微球CPVA-g-PMAA对代谢分子肌酐(Cr)及药物分子5-氟尿嘧啶(5-FU)的吸附性能,分析了吸附机理.实验结果表明,较大的pH值范围内,接枝微球CPVA-g-PMAA的zeta电位为绝对值较大的负值,即其表面携带高密度的负电荷.受静电相互作用的驱动,接枝微球CP-VA-g-PMAA对含N的Cr及5-FU分子表现出很强的吸附能力.     

The influence of the structure and the composition of water/AOT-Tween 85/IPM microemulsion system on transdermal delivery of 5-fluorouracil

The purpose of this study was to investigate the influence of the structure and the composition of water/Aerosol-OT (AOT)-Tween 85/isopropylmyristate (IPM) microemulsion system (WATI) on transdermal delivery of 5-fluorouracil (5-FU). The structure of WATI was characterized by measuring surface tension, density, viscosity, electric conductivity, and differential scanning calorimetry. The effect of the drug loading, water content, component compositions and the amount of mixed surfactant on permeation of 5-FU through mice skin was evaluated by using Franz-type diffusion cells. The results in vitro implied that WATI was W/O microemulsion when the water content was below 20 wt% at fixed 20 wt% of mixed surfactant at 25°C, then might be transformed to a bicontinuous structure, finally, formed O/W microemulsion with water content over 30 wt%. Increase of the drug loading can directly facilitate the penetration of the drug across the skin. Drug diffusion after 12?h from the bicontinuous microemulsion (795.1?±?22.3 µg·cm^?2) would be fastest compared to that from the W/O microemulsion (650.2?±?11.7 µg·cm^?2) and the O/W microemulsion (676.6?±?14.8 µg·cm^?2). The combination of AOT and IPM could bring about synergistic effect on the skin enhancement, however, Tween 85 in WATI decreased the cumulative permeation amount of 5-FU. The content of mixed surfactant had no effect on the permeation of 5-FU at fixed surfactant/cosurfactant ratio (K_m?=?2). Thus, the increased transdermal delivery the hydrophilic drug of 5-FU was found to be concerned with both of the structure and the composition of WATI.     

Manganese-doped ZnSe quantum dots as a probe for time-resolved fluorescence detection of 5-fluorouracil

Quantum dots (QDs) are generally used for the conventional fluorescence detection. However, it is difficult for the QDs to be applied in time-resolved fluorometry due to their short-lived emission. In this paper, high-quality Mn-doped ZnSe QDs with long-lived emission were prepared using a green and rapid microwave-assisted synthetic approach in aqueous solution. Fluorescence lifetime of the Mn-doped ZnSe QDs was extended as long as 400 μs, which was 10,000 times higher than that of conventional QDs such as CdS, CdSe, and CdTe. The QDs exhibited an excellent photostability over 35 h under continuous irradiation at 260 nm. Capped with mercaptopropionic acid (MPA), the Mn-doped ZnSe QDs were used for the time-resolved fluorescence detection of 5-fluorouracil (5-FU) with the detection limit of 128 nM. The relative standard deviation for seven independent measurements of 1.5 μM 5-FU was 3.8%, and the recovery ranged from 93% to 106%. The results revealed that the Mn-doped ZnSe QDs could be a good candidate as a luminescence probe for highly sensitive time-resolved fluorometry.