Influence of cationic lipids on the stability and membrane properties of paclitaxel‐containing liposomes

Campbell, R. B.; Balasubramanian, Sathyamangalam V.; Straubinger, Robert M.

doi:10.1002/jps.1063

Cited by 117 publications

(82 citation statements)

References 35 publications

(82 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During storage at 25°C, C300(−), conventional liposomes exhibited a rapid increase of mean droplet size and PI, in consistent with other studies showing the formulation instability of PTX-loaded liposomes. 13,[17][18][19]37 In contrast, no significant changes were found in C300(+) liposomes: after 4 days, the mean size and PI of C300(−) liposomes increased by 2.5-and 1.8-fold while no significant changes were observed in C300(+) liposomes ( Figure 1B and C). These data indicate that C300 incorporation blocked PTXtriggered destabilization of liposomes.…”

mentioning

confidence: 89%

Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

Hong

Choi

Kim

et al. 2016

IJN

View full text Add to dashboard Cite

Studies have highlighted the challenge of developing injectable liposomes as a paclitaxel (PTX) carrier, a challenge attributable to the limitations in liposomal stability caused by PTX loading. Poor stability of PTX-loaded liposomes is caused by PTX-triggered aggregation or fusion of liposomal membranes and is exacerbated in the presence of PEGylated lipid. In the present study, the effect of triglyceride incorporation on the stability of PTX-loaded/PEGylated liposomes was explored. Incorporation of a medium chain triglyceride Captex 300 into saturated phosphatidylcholine (PC)-based liposomes (1,2-dimyristoyl- sn -glycero-3-phosphocholine [DMPC]:cholesterol [CHOL]:N-(Carbonyl-methoxypolyethyleneglycol 2000)-1, 2-distearoyl- sn -glycero-3-phospho-ethanolamine [PE-PEG]), produced a fine, homogeneous, and membrane-filterable PTX-loaded liposomes fulfilling the requirement of an injectable lipid formulation. Triglyceride incorporation also greatly inhibited the time-dependent leakage of PTX from saturated PC-based liposomes, which appears to be mediated by the inhibition of liposome fusion. In contrast, triglyceride incorporation induced the destabilization and PTX leakage of unsaturated PC-based liposomes, indicating the opposite effect of triglyceride depending on the fluidity status of PC constituting the liposomal membrane. PTX release profile and the in vitro and in vivo anticancer efficacy of triglyceride-incorporated DMPC:CHOL:PE-PEG liposomes were similar to Taxol ® while the toxicity of liposomal PTX was significantly lower than that of Taxol. Taken together, triglyceride incorporation provided an injectable PTX formulation by functioning as a formulation stabilizer of PEGylated/saturated PC-based liposomes.

show abstract

mentioning

confidence: 89%

Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

Hong

Choi

Kim

et al. 2016

IJN

View full text Add to dashboard Cite

show abstract

“…Liposomal formulations of paclitaxel can be physically unstable above certain drug:lipid ratios. 17,28 The liposomes used here were stable over a time period that greatly exceeded the duration of the experiments. Nonetheless, physical stability and the absence of precipitated drug were verified prior to administration using circular dichroism (CD) and differential interference contrast microscopy assays, which we have described previously.…”

Section: Preparation Of Paclitaxel Liposomesmentioning

confidence: 99%

“…Nonetheless, physical stability and the absence of precipitated drug were verified prior to administration using circular dichroism (CD) and differential interference contrast microscopy assays, which we have described previously. [28][29][30][31] The size distribution of the liposome population was determined by quasielastic light scattering (Nicomp 380, PSSNicomp, Santa Barbara, CA) using the Nicomp fitting algorithm. A bimodal distribution best fit the data: 59% of the population had a mean diameter of approximately 900 nm (range 630-1400 nm), and 39% had a mean diameter of approximately 200 nm (range 130-250 nm).…”

Section: Preparation Of Paclitaxel Liposomesmentioning

confidence: 99%

Pharmacokinetics of paclitaxel-containing liposomes in rats

Fetterly

Straubinger

2003

AAPS PharmSci

Self Cite

View full text Add to dashboard Cite

In animal models, liposomal formulations of paclitaxel possess lower toxicity and equal antitumor efficacy compared with the clinical formulation, Taxol. The goal of this study was to determine the formulation dependence of paclitaxel pharmacokinetics in rats, in order to test the hypothesis that altered biodistribution of paclitaxel modifies the exposure of critical normal tissues. Paclitaxel was administered intravenously in either multilamellar (MLV) liposomes composed of phosphatidylglycerol/phosphatidylcholine (L-pac) or in the Cremophor EL/ethanol vehicle used for the Taxol formulation (Cre-pac). The dose was 40 mg/kg, and the infusion time was 8 to 9 minutes. Animals were killed at various times, and pharmacokinetic parameters were determined from the blood and tissue distribution of paclitaxel. The area under the concentration vs time curve (AUC) for blood was similar for the 2 formulations (L-pac: 38.1 ± 3.32 μg-h/mL; Cre-pac: 34.5 ± 0.994 μg-h/mL), however, the AUC for various tissues was formulation-dependent. For bone marrow, skin, kidney, brain, adipose, and muscle tissue, the AUC was statistically higher for Cre-pac. For spleen, a tissue of the reticuloendothelial system that is important in the clearance of liposomes, the AUC was statistically higher for L-pac. Apparent tissue partition coefficients (K p ) also were calculated. For bone marrow, a tissue in which paclitaxel exerts significant toxicity, K p was 5-fold greater for paclitaxel in Cre-pac. The data are consistent with paclitaxel release from circulating liposomes, but with efflux delayed sufficiently to retain drug to a greater extent in the central (blood) compartment and reduce penetration into peripheral tissues. These effects may contribute to the reduced toxicity of liposomal formulations of paclitaxel.

show abstract

“…Cremophor EL has been reported to elicit various side effects in patients, including hypersensitivity, nephrotoxicity, and neurotoxicity [13]. Various formulations of PCT, such as polymeric micro/nanospheres [14,15], liposomes [16,17], microemulsions [18] and polymeric micelles [19][20][21] have been developed to increase the solubility of PCT, minimize its side effects, and decrease its systemic clearance.…”

Section: Introductionmentioning

confidence: 99%

Mixed PEG–PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs: Improved drug solubilization and enhanced in vitro cytotoxicity

Sawant

Torchilin

2008

European Journal of Pharmaceutics and Biopharmaceutics

View full text Add to dashboard Cite

Two poorly soluble, potent anticancer drugs, paclitaxel and camptothecin, were successfully solubilized by mixed micelles of polyethylene glycol-phosphatidyl ethanolamine (PEG-PE) and vitamin E. Drug containing micelles were additionally modified with anti-nucleosome monoclonal antibody 2C5 (mAb 2C5), which can specifically bring micelles to tumor cells in vitro. The optimized micelles had an average size of about 13-to-22 nm and the immuno-modification of micelles did not significantly change it. The solubilization of both drugs by the mixed micelles was more efficient than by micelles made of PEG-PE alone. Solubilization of camptothecin in micelles prevented also the hydrolysis of active lactone form of the drug to inactive carboxylate form. Drug loaded mixed micelles and mAb 2C5-immunomicelles demonstrated significantly higher in vitro cytotoxicity than free drug against various cancer cell lines.

show abstract

Influence of cationic lipids on the stability and membrane properties of paclitaxel‐containing liposomes

Cited by 117 publications

References 35 publications

Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

Development of paclitaxel-loaded liposomal nanocarrier stabilized by triglyceride incorporation

Pharmacokinetics of paclitaxel-containing liposomes in rats

Mixed PEG–PE/vitamin E tumor-targeted immunomicelles as carriers for poorly soluble anti-cancer drugs: Improved drug solubilization and enhanced in vitro cytotoxicity

Contact Info

Product

Resources

About