Development and characterization of a novel Cremophor ® EL free liposome-based paclitaxel (LEP-ETU) formulation (original) (raw)
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International Journal of Applied Pharmaceutics, 2023
Objective: Liposomes are the controlled-release dosage form that improves the therapeutic efficacy of the drugs, prolongs the duration of action, reduces dosage frequency, and improves patient compliance. Methods: The thin-film hydration method was used to prepare Paclitaxel liposomes. In this process, cholesterol and sodium deoxycholate were used for the formulation, while chloroform and methanol were used as diluents. Percentage (%) drug release study was carried out in phosphate buffer at pH 7.4 in USP apparatus II (Paddle type)Model no VDA-8D, Veego, Mumbai, India. Results: Paclitaxel liposomes of various batches showed a percentage yield ranging from 38 to 84%. It was observed that (Encapsulation efficiency)EE% of Batches B1 to B10 were 0
INFLUENCE OF LIPOSOME COMPOSITION ON PACLITAXEL ENTRAPMENT AND pH SENSITIVITY OF LIPOSOMES
2015
Abstract: The objective of the present investigation was to study the effect of composition of phospholipids on drug entrapment efficiency and pH sensitivity. In the present study, paclitaxel containing liposomes of different phospholipid compositions were formulated and compared. The formulation composed of Phospholipon 90G/DOPE/CHEMS 8:2:2(D) containing paclitaxel and lipids in the molar ratio of 1:30 (drug: lipid) was found to have good incorporation efficiency(94%). The highest paclitaxel concentration achievable in the liposomal formulation was 1.5 mg/ml. Liposomes with phospholipon 90 G alone couldn’t show pH sensitivity. Formulation B (Phospholipon 90G /DOPE 8:2) released drug at pH 5.5, but was unstable at pH 7.5. On inclusion of CHEMS, liposomes were stabilized at physiological pH, and released paclitaxel at lower pH. Thus including CHEMS into liposomal formulation of paclitaxel, composed of Phospholipon 90 G/DOPE has proved to be the most efficient pH sensitive system with...
A Strategic Process Development and in Vitro Cytotoxicity Analysis of Paclitaxel-Loaded Liposomes
International Journal of Applied Pharmaceutics
Objective: Liposomes are the controlled-release dosage form that improves the therapeutic efficacy of the drugs, prolongs the duration of action, reduces dosage frequency, and improves patient compliance. Methods: The thin-film hydration method was used to prepare Paclitaxel liposomes. In this process, cholesterol and sodium deoxycholate were used for the formulation, while chloroform and methanol were used as diluents. Percentage (%) drug release study was carried out in phosphate buffer at pH 7.4 in USP apparatus II (Paddle type)Model no VDA-8D, Veego, Mumbai, India. Results: Paclitaxel liposomes of various batches showed a percentage yield ranging from 38 to 84%. It was observed that (Encapsulation efficiency)EE% of Batches B1 to B10 were 0,62.33,59.51,50.21,44.30,82.25,88.95,72.34,77.37 and 70.63 percentage, respectively. Data fitting to the Peppas, Higuchi, 1st-order, and zero-order models was used to examine the optimized liposome (B7) release kinetic mechanism. Data compariso...
Enhanced solubility and stability of PEGylated liposomal paclitaxel: in vitro and in vivo evaluation
International journal of pharmaceutics, 2007
An improved PEGylated liposomal formulation of paclitaxel has been developed with the purpose of improving the solubility of paclitaxel as well as the physicochemical stability of liposome in comparison to the current Taxol formulation. The use of 3% (v/v) Tween 80 in the hydration media was able to increase the solubility of drug. The addition of sucrose as a lyoprotectant in the freeze-drying process increased the stability of the liposome particles. There was no significant difference in the entrapment efficiency of paclitaxel between the conventional non-PEGylated liposomes and our PEGylated liposomes. Cytotoxicity in human breast cancer cell lines (MDA-MB-231 and SK-BR-3) of our paclitaxel formulation was less potent compared to Taxol after 24h incubation, but was equipotent after 72 h due to the slower release of drug from the liposome. Our PEGylated liposomes increased the biological half-life of paclitaxel from 5.05 (+/-1.52)h to 17.8 (+/-2.35)h compared to the conventional ...
Journal of Pharmaceutical Sciences, 2001
Paclitaxel (taxol) is a poorly soluble anticancer agent that is in widespread clinical use. Liposomes provide a less toxic vehicle for solubilizing the drug and increasing the therapeutic index of paclitaxel in model tumor systems. The role of liposome membrane composition in the stability of paclitaxel-containing formulations is understood partially for neutral and anionic liposomes, but poorly for other compositions. We investigated the effect of dialkyl cationic lipids on the stability and physical properties of paclitaxel-containing liposomes, using circular dichroism (CD),¯uorescence spectroscopy, and differential interference contrast microscopy (DIC). DOTAP (1,2-dioleoyl-3-trimethylammonium propane), a cationic lipid used frequently for gene delivery, was combined at various ratios with dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), or distearoylphosphatidylcholine (DSPC). In the absence of DOTAP, the stability of liposomes containing !3 mol% paclitaxel was observed to follow the following rank order: DPPC b DSPC b DMPC. Increasing concentrations of DOTAP increased the physical stability of all compositions, and maximal stabilization was achieved at 30±50 mol% DOTAP, depending on the paclitaxel concentration and the acyl chain length of the phosphatidylcholine. The relationship between stability and mole fraction of DOTAP was complex for some compositions. DOTAP exerted a major¯uidizing effect on DMPC, DPPC, and DSPC membranes, and the addition of paclitaxel at 3±8 mol% did not increase¯uidity further. Studies of membrane phase domain behavior using the probe Laurdan (6-dodecanoyl-2-dimethylaminonaphthalene) indicated that both paclitaxel and DOTAP were miscible with the phosphatidylcholine phase. The physical events leading to destabilization of formulations are hypothesized to arise from concentration-dependent paclitaxel self-association rather than immiscibility of the membrane lipids. Given the increased incorporation and stability of paclitaxel in DOTAP-containing membranes and the potential for enhanced interaction with cells, cationic liposomes may provide a therapeutic advantage over previously described liposome formulations.
Development of nonionic surfactant/phospholipid o/w emulsion as a paclitaxel delivery system
Journal of Controlled Release, 1999
Paclitaxel is an anticancer agent with low aqueous solubility. More extensive clinical use of this drug is somewhat delayed due to lack of appropriate delivery vehicles. An attempt was made to adopt an o / w emulsion as the drug carrier which incorporated paclitaxel in the triacylglycerol stabilized by a mixed-emulsifier system. A suitable formulation was found in this study: 0.75 mg / ml paclitaxel, 10% (w / v) oil blend, 4% (w / v) EPC, 3% (w / v) Tween 80 in 2.25% (w / v) glycerol solution. The formulated emulsion has very good stability when stored at 48C, and the paclitaxel containment efficiency can be maintained above 95% and the mean emulsion diameter around 150 nm for at least 3 months. Paclitaxel-emulsion displayed cytotoxicity against HeLa cells with IC at 30 nM. The average life span of ascitic-tumor-bearing mice was 50 prolonged significantly by the treatment of paclitaxel-emulsion (P,0.05). The formulated emulsion is a promising carrier for paclitaxel and other lipophilic drugs.
Efficacy and Toxicological Studies of Cremophor EL Free Alternative Paclitaxel Formulation
Current Drug Safety, 2011
Purpose: In the present study, Cremophor EL free paclitaxel elastic liposomal formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate was developed and optimized. The toxicological profile, antitumor efficacy and hemolytic toxicity of paclitaxel elastic liposomal formulation in comparison to Cremophor EL based marketed formulation were evaluated. Methods: Paclitaxel elastic liposomal formulations were prepared and characterized in vitro, ex-vivo and in vivo. Single dose toxicity study of paclitaxel elastic liposomal and marketed formulation was carried out in dose range of 10, 20, 40, 80, 120, 160 and 200 mg/kg. Cytotoxicity of developed formulation was evaluated using small cell lung cancer cell line (A549). Antitumor activity of developed formulation was compared with the marketed formulation using Cytoselect TM 96-well cell transformation assay. Results: In vivo administration of paclitaxel elastic liposomal formulation into mice showed 6 fold increase in Maximum Tolerated Dose (MTD) in comparison to the marketed formulation. Similarly, LD 50 (141.6 mg/kg) was also found to increase significantly than the marketed formulation (16.7 mg/kg). Result of antitumor assay revealed a high reduction of tumor density with paclitaxel elastic liposomal formulation. Reduction in hemolytic toxicity was also observed with paclitaxel elastic liposomal formulation in comparison to the marketed formulation. Conclusion: The carrier based approach for paclitaxel delivery demonstrated significant reduction in toxicity as compared to the Cremophor EL based marketed formulation following intra-peritoneal administration in mice model. The reduced toxicity and enhanced anti-cancer activity of elastic liposomal formulation strongly indicate its potential for safe and effective delivery of paclitaxel.
Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery
Journal of Pharmaceutical Sciences, 2009
Nonionic surfactant based vesicles (niosomes) are novel drug delivery systems formed from the self-assembly of nonionic amphiphiles in aqueous media. In the present study niosomal formulations of Paclitaxel (PCT), an antineoplastic agent, were prepared using different surfactants (Tween 20, 60, Span 20, 40, 60, Brij 76, 78, 72) by film hydration method. PCT was successfully entrapped in all of the formulations with encapsulation efficiencies ranging between 12.1 AE 1.36% and 96.6 AE 0.482%. Z-average sizes of the niosomes were between 229.3 and 588.2 nm. Depending on the addition of the negatively charged dicetyl phosphate to the formulations negative zeta potential values were obtained. High surface charges showed that niosomes can be suspended in water well and this is beneficial for their storage and administration. PCT released from niosomes by a diffusion controlled mechanism. The slow release observed from these formulations might be beneficial for reducing the toxic side effects of PCT. The niosome preparation method was found to be repeatable in terms of size distribution, zeta potential and % drug loading values. The efficiency of niosomes to protect PCT against gastrointestinal enzymes (trypsin, chymotrypsin, and pepsin) was also evaluated for PCT oral delivery. Among all formulations, gastrointestinal stability of PCT was well preserved with Span 40 niosomes.
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.