Development of nonionic surfactant/phospholipid o/w emulsion as a paclitaxel delivery system (original) (raw)
Related papers
Formulation development and antitumor activity of a filter-sterilizable emulsion of paclitaxel
Pharmaceutical research, 2000
Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol:surfactant:saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. Alternative drug delivery systems, including parenteral emulsions, are under development in recent years to reduce drug toxicity, improve efficacy and eliminate premedication. Paclitaxel emulsions were prepared by high-shear homogenization. The particle size of the emulsions was measured by dynamic light scattering. Drug concentration was quantified by HPLC and in vitro drug release was monitored by membrane dialysis. The physical stability of emulsions was monitored by particle size changes in both the mean droplet diameter and 99% cumulative distribution. Paclitaxel potency and changes in the concentration of known degradants were used as chemical stability indicators. Single dose acute toxicity studies were conducted in healthy mice and efficacy studies in B 16 melanoma tu...
Improved Oral Delivery of Paclitaxel Following Administration in Nanoemulsion Formulations
Journal of Nanoscience and Nanotechnology, 2006
Nanoemulsion formulations were designed for enhancing the oral bioavailability of hydrophobic drugs. Paclitaxel was selected as a model hydrophobic drug, which is also a substrate for the P-glycoprotein efflux system. The oil-in-water (o/w) nanoemulsions were formulated with pine nut oil as the internal oil phase, egg lecithin as the primary emulsifier, and water as the external phase. Stearylamine and deoxycholic acid were used to impart positive and negative charge to the emulsions, respectively. Nanoemulsions were prepared by sonication method and characterized for particle size and surface charge. The control and nanoemulsion formulations with tritiated [3H]-paclitaxel were administered orally to female C57BL/6 mice and the distribution of the drug was examined. The formulated nanoemulsions had a particle size range of ∼90–120 nm (laser diffraction method)and zeta potential values ranging from −56 mV to +34 mV. Following oral administration, a significantly higher concentration ...
Journal of Pharmacy and Pharmacology, 2002
A cholesterol-rich emulsion (LDE) is taken up by malignant cells which over-express low-density lipoprotein (LDL) receptors and thus may be used as a carrier for drugs directed against neoplastic cells. In this study, we associated the antineoplastic agent paclitaxel to LDE and analysed the new formulation's incorporation efficiency, chemical and physical stability, cellular uptake and cytostatic activity against a neoplastic cell line and the acute toxicity to rats. A paclitaxel incorporation efficiency of approximately 75% was achieved when paclitaxel was mixed with LDE at a 6:1 lipid-to-drug molar ratio. The association of paclitaxel with LDE increased by 54% the mean diameter of the emulsion particles but did not damage the paclitaxel chemical structure as analysed by HPLC. Results from gradient ultracentrifugation and Sephadex G25 gel filtration indicated that the binding of the drug to the emulsion was stable. It was shown that the cellular uptake and the cytotoxic activit...
Effect of lipid on physicochemical properties of solid lipid nanoparticle of paclitaxel
Journal of Pharmaceutical Investigation, 2012
The aim of this study was to compare physicochemical properties of solid lipid nanoparticles (SLNs) on drug nature. These SLNs were fabricated for formulating paclitaxel (PTX) or docetaxel (DTX). To make small, and highly encapsulated SLNs, the SLNs consisted of compritol 888 ATO (glyceryl behenate) as lipid matrix, poloxamer 188 or solutol HS 15 as surfactant and soya lecithin as co-surfactant. The SLNs were characterized by particle size, zeta potential, in vitro release study and cytotoxicity study. In this study, SLNs showed different physicochemical properties and release profiles according to used solid lipid. In case of particle size, PS1 and DS1 showed bigger particle size than those of PS2 and DS2. Encapsulation efficiency (%) of DTX-loaded SLNs exhibited higher than that of PTX-loaded SLNs. And, DTXloaded SLNs showed prolonged release up to 24 h. We found that SLN using solutol HS 15 as surfactant exhibited enhanced cellular uptake on MCF-7/ADR cells. These results suggest that different drugs and surfactant effect on physicochemical properties regardless same composition.
Comparative study of solid lipid nanoparticles and nanostructured lipid carriers for in vitro Paclitaxel delivery
Lipid nanoparticles are promising carriers to deliver anticancer agents of low aqueous solubility such as Paclitaxel (PTX). The aim of this work is to improve the efficacy of Paclitaxel through formulation of Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) containing two different liquid lipids. Preparation was done using homogenization and ultrasonication technique. Nanoparticles physical characterization was done by determination of the mean particle size, zeta potential and Transmission electron microscopy (TEM). Entrapment efficiency and Differential Scanning Calorimetry (DSC) was determined. In vitro release and cytotoxicity was done and results were compared to the commercially available product Taxol ® .The mean particle diameter was between 276-314 nm, while zeta potential ranged from-20.2 and-24.9 mV. The entrapment efficiencies of prepared formulae were high(up to 87.6%) and thermal analysis revealed that the drug was in amorphous form. In vitro release through dialysis membrane showed prolonged release. In vitro cytotoxicity assay showed that IC50 of PTX-NLCs was significantly lower than that of Taxol ®. NLC containing Capryol 90 had the best results in entrapment efficiency and lowest IC50. Both SLN and NLC can be potential carriers for prolonged release and to enhance activity of PTX.
In vivo evaluation of lipid nanocapsules as a promising colloidal carrier for paclitaxel
International Journal of Pharmaceutics, 2007
Paclitaxel-loaded lipid nanocapsules (PX-LNC) exhibit interesting in vitro characteristics with improved antitumoral activity compared with free PX formulation. Biodistribution studies were realized with the use of 14 C-trimyristin ( 14 C-TM) or 14 C-phosphatidylcholine ( 14 C-PC) whereas antitumoral activity of PX-LNC formulations was based on the animal survival in a chemically induced hepatocellular carcinoma (HCC) model in Wistar rats. Blood concentration-time profiles for both labeled 14 C-TM-LNC and 14 C-PC-LNC were similar; the t 1/2 and MRT values (over 2 h and close to 3 h, respectively, for both formulations) indicated the long circulating properties of the LNC carrier with a slow distribution and elimination phase. Survival curves of paclitaxel treated groups showed a statistical significant difference compared to the control survival curve (P = 0.0036 and 0.0408). Animals treated with 4× 70 mg/m 2 of PX-LNC showed the most significant increase in mean survival times compared to the controls (IST mean 72%) and cases of long-term survivors were preferentially observed in the PX-LNC treated group (37.5%; 3/8). These results demonstrate the great interest to use LNC as drug delivery system for paclitaxel, permitting with an equivalent therapeutic efficiency to avoid the use of excipients such as polyoxyethylated castor oil for its formulation.
Enhanced stability of nano-emulsified paclitaxel
2011
The main goal of this work was to develop an optimal self-microemulsifying paclitaxel prepared with PLGA and solubilizer such as tetraglycol, Cremophor ELP, and Labrasol. The prepared PTx-loaded SMES showed the size of the range of 80-130 nm by dynamic light scattering and a spherical shape by atomic force microscopy. In experiment of storage stability in deionized water (DW) or blood condition, PTx-loaded SMES showed good stability in DW and comparable stability in blood condition at 37˚C for 7 days. In addition, PTx-loaded SMES showed a significant inhibitory effect on B16F10 melanoma proliferation. In conclusion, we confirmed that the formulations tried in this study could be used as administration form for animal trials of PTx.
Die Pharmazie, 2009
This study investigates the design and characterization of solid lipid nanoparticles (SLNs) containing paclitaxel fabricated by a modified solvent injection technique using stearic acid as lipid and stabilized by a mixture of surfactants, for future evaluation of this colloidal carrier system for the oral delivery of paclitaxel, devoid of the side effects of Cremophor EL. SLN formulations of paclitaxel stabilized by mixture of surfactants i.e. lecithin/poloxamer 188 were developed with smaller size and narrow size distribution. The paclitaxel-loaded SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The average particle size obtained through this method was found to be approximately 113 nm. The zeta potential was between -32 and -39 mV with poloxamer 188. Encapsulation efficiencies of about 72.18 +/- 3.7 and 89.0 +/- 2.4% were achieved using 0.05 and 0.25 mmol of paclitaxel, respectively. Paclitaxel showed a sustained in vitro r...
International Journal of Applied Pharmaceutics
Objective: This study was aimed to design and characterize Paclitaxel-loaded Solid Lipid Nanoparticles (SLNs) to achieve site specificity,reduce toxicity and sustained release pattern. Methods: Paclitaxel-loaded solid lipid nanoparticles were fabricated by microemulsion followed by probe sonication technique using stearic acid as lipid and stabilized of the mixture of surfactants. In this study, 32 full factorial design was employed for optimizing the concentration of lipid as stearic acid and surfactant (soya lecithin) for the nanoparticles. The optimization was done by studying the dependent variable of particle size and % entrapment efficiency. Results: The results showed that the paclitaxel-loaded solid lipid nanoparticles prepared with the concentration of 33.31 % stearic acid and 500 mg of soya lecithin were optimum characteristic than other formulations. They showed the average particles size 149±4.10 nm and PDI 250±2.04. The zeta potential, % EE and % drug loading capacity w...
Development of Lipid-Based Nanoparticles for Enhancing the Oral Bioavailability of Paclitaxel
AAPS PharmSciTech, 2011
The current research work investigates the potential of solid lipid nanoparticles (SLNs) in improving the oral bioavailability of paclitaxel. Paclitaxel-loaded SLNs (PTX-SLNs) were prepared by modified solvent injection method using stearylamine as lipid, soya lecithin and poloxamer 188 as emulsifiers. SLNs were characterized in terms of surface morphology, size and size distribution, surface chemistry and encapsulation efficiency. Pharmacokinetics and bioavailability studies were conducted in male Swiss albino mice after oral administration of PTX-SLNs. SLNs exhibited spherical shape with smooth surface as analyzed by transmission electron microscopy (TEM). The mean particle size of SLNs was 96±4.4 nm with a low polydispersity index of 0.162±0.04 and zeta potential of 39.1±0.8 mV. The drug entrapment efficiency was found to be 75.42±1.5% with a loading capacity of 31.5±2.1% (w/w). Paclitaxel showed a slow and sustained in vitro release profile and followed Higuchi kinetic equations. After oral administration of the PTX-SLNs, drug exposure in plasma and tissues was ten-and twofold higher, respectively, when compared with free paclitaxel solution. PTX-SLNs produced a high mean C max (10,274 ng/ml) compared with that of free paclitaxel solution (3,087 ng/ml). The absorbed drug was found to be distributed in liver, lungs, kidneys, spleen, and brain. The results suggested that PTX-SLNs dispersed in an aqueous environment are promising novel formulations that enhanced the oral bioavailability of hydrophobic drugs, like paclitaxel and were quite safe for oral delivery of paclitaxel as observed by in vivo toxicity studies.