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Clinical Therapeutics Dec 2013Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have... (Comparative Study)
Comparative Study Randomized Controlled Trial
Bioequivalence of Liposome-Entrapped Paclitaxel Easy-To-Use (LEP-ETU) formulation and paclitaxel in polyethoxylated castor oil: a randomized, two-period crossover study in patients with advanced cancer.
BACKGROUND
Preclinical studies comparing paclitaxel formulated with polyethoxylated castor oil with the sonicated formulation of liposome-entrapped paclitaxel (LEP) have demonstrated that LEP was associated with reduced toxicity while maintaining similar efficacy. Preliminary studies on the pharmacokinetics in patients support earlier preclinical data, which suggested that the LEP Easy-to-Use (LEP-ETU) formulation and paclitaxel formulated with castor oil may have comparable pharmacokinetic properties.
OBJECTIVES
Our objectives were: (1) to determine bioequivalence of paclitaxel pharmaceutically formulated as LEP-ETU (test) and paclitaxel formulated with castor oil (reference); and (2) to assess the tolerability of LEP-ETU following intravenous administration.
METHODS
Patients with advanced cancer were studied in a randomized, 2-period crossover bioequivalence study. Patients received paclitaxel 175 mg/m(2) administered as an intravenous infusion over 180 minutes, either as a single-treatment cycle of the test formulation followed by a single-treatment cycle of the reference formulation, or vice versa.
RESULTS
Thirty-two of 58 patients were evaluable and were included in the analysis for bioequivalence. Mean total paclitaxel Cmax values for the test and reference formulations were 4955.0 and 5108.8 ng/mL, respectively. Corresponding AUC0-∞ values were 15,853.8 and 18,550.8 ng·h/mL, respectively. Treatment ratios of the geometric means were 97% (90% CI, 91%-103%) for Cmax and 84% (90% CI, 80%-90%) for AUC0-∞. These results met the required 80% to 125% bioequivalence criteria. The most frequently reported adverse events after LEP-ETU administration were fatigue, alopecia, and myalgia.
CONCLUSION
At the studied dose regimen, LEP-ETU showed bioequivalence with paclitaxel formulated with polyethoxylated castor oil.
Topics: Adult; Aged; Antineoplastic Agents; Castor Oil; Chemistry, Pharmaceutical; Cross-Over Studies; Drug Administration Schedule; Female; Humans; Infusions, Intravenous; Liposomes; Male; Middle Aged; Neoplasm Metastasis; Neoplasms; Paclitaxel; Solvents; Therapeutic Equivalency; Young Adult
PubMed: 24290734
DOI: 10.1016/j.clinthera.2013.10.009 -
European Journal of Pharmaceutics and... Nov 2023Pancreatic cancer (PC) is an incurable disease with a high death rate in the world nowadays. Gemcitabine (GEM) and Paclitaxel (PTX) are considered as references of... (Review)
Review
Pancreatic cancer (PC) is an incurable disease with a high death rate in the world nowadays. Gemcitabine (GEM) and Paclitaxel (PTX) are considered as references of chemotherapeutic treatments and are commonly used in clinical applications. Factors related to the tumor microenvironment such as insufficient tumor penetration, toxicity, and drug resistance can limit the effectiveness of these therapeutic anticancer drugs. The use of different liposomal nanostructures is a way that can optimize the drug's effectiveness and reduce toxicity. Given the development of PC therapy, this review focuses on advances in Nano-formulation, characterization, and delivery systems of loaded GEM and PTX liposomes using chemotherapy, nucleic acid delivery, and stroma remodeling therapy. As a result, the review covers the literature dealing with the applications of liposomes in PC therapy.
Topics: Humans; Gemcitabine; Paclitaxel; Liposomes; Deoxycytidine; Cell Line, Tumor; Pancreatic Neoplasms; Nanostructures; Tumor Microenvironment
PubMed: 37758121
DOI: 10.1016/j.ejpb.2023.09.014 -
Nanomedicine (London, England) Apr 2023To overcome the resistance of lung cancer to paclitaxel. P-glycoprotein antibody-conjugated paclitaxel PEG-coated immunoliposomes (Pab-PTX-L) were prepared, and a...
To overcome the resistance of lung cancer to paclitaxel. P-glycoprotein antibody-conjugated paclitaxel PEG-coated immunoliposomes (Pab-PTX-L) were prepared, and a series of quality evaluations, cell evaluation and assessment of their antitumor effect in mice were conducted. The results showed that Pab-PTX-L was nano-sized with high encapsulation efficiency of paclitaxel. For the paclitaxel-resistant lung cancer A549/T cells, the cellular uptake and cell viability inhibition and apoptosis of Pab-PTX-L-treated cells were higher than those of the control groups. More importantly, Pab-PTX-L showed a good targeting and antitumor effect on tumor tissue in mouse experiments. This study will provide a new insight on enhanced paclitaxel delivery into paclitaxel-resistant cancer cells.
Topics: Animals; Mice; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Drug Delivery Systems; Drug Resistance, Neoplasm; Liposomes; Lung Neoplasms; Paclitaxel; Drug Resistance, Multiple; Antibodies; Male; Mice, Nude; Mice, Inbred BALB C
PubMed: 37306214
DOI: 10.2217/nnm-2023-0015 -
Future Oncology (London, England) Dec 2013Currently, six liposomal chemotherapeutics have received clinical approval and many more are in clinical trials or undergoing preclinical evaluation. Liposomes exhibit... (Review)
Review
Currently, six liposomal chemotherapeutics have received clinical approval and many more are in clinical trials or undergoing preclinical evaluation. Liposomes exhibit low toxicity and improve the biopharmaceutical features and therapeutic index of drugs, thereby increasing efficacy and reducing side effects. In this review we discuss the advantages of using liposomes for the delivery of chemotherapeutics. Gemcitabine and paclitaxel have been chosen as examples to illustrate how the performance of a metabolically unstable or poorly water-soluble drug can be greatly improved by liposomal incorporation. We look at the beneficial effects of liposomes in a variety of solid and blood-borne tumors, including thyroid cancer, pancreatic cancer, breast cancer and multiple myeloma.
Topics: Breast Neoplasms; Deoxycytidine; Doxorubicin; Drug Delivery Systems; Female; Humans; Liposomes; Multiple Myeloma; Paclitaxel; Pancreatic Neoplasms; Thyroid Neoplasms; Gemcitabine
PubMed: 24295415
DOI: 10.2217/fon.13.146 -
Critical Reviews in Oncogenesis 2014We review liposome-based delivery approaches that aim to address toxicities and to improve the therapeutic efficacy of mainstream chemotherapeutics, namely, doxorubicin,... (Review)
Review
We review liposome-based delivery approaches that aim to address toxicities and to improve the therapeutic efficacy of mainstream chemotherapeutics, namely, doxorubicin, paclitaxel, and cisplatin. A brief review of the biomolecular mechanism(s) of action of these agents is followed by a description of characteristic examples of therapeutic approaches and of liposome membrane designs. Short reports on clinical studies are also included when applicable. The technical issues of different loading/encapsulation methods of these agents into liposomes are also discussed in terms of the physicochemical properties of both the agents themselves and of the lipid-based self-assemblies.
Topics: Antineoplastic Agents; Cisplatin; Doxorubicin; ErbB Receptors; Humans; Hydrogen-Ion Concentration; Liposomes; Paclitaxel
PubMed: 25271431
DOI: 10.1615/critrevoncog.2014011533 -
Colloids and Surfaces. B, Biointerfaces Dec 2017In this study, novel paclitaxel (PTX) loaded hybrid liposomes for oral PTX delivery were prepared through incorporating PTX loaded polyion complex micelles comprised of...
In this study, novel paclitaxel (PTX) loaded hybrid liposomes for oral PTX delivery were prepared through incorporating PTX loaded polyion complex micelles comprised of positively charged Pluronic F127-Polyethylenimine (PF127-PEI) copolymer and negatively charged sodium cholate (CA) into liposomes consisted of phospholipid molecules. According to the results, this kind of PTX-loaded hybrid liposomes showed improved PTX encapsulation efficiency, sustained PTX release, and enhanced PTX absorption in intestine. The mechanism for enhancing absorption was demonstrated in connection with inhibition of the efflux mediated by multidrug resistance protein, intestinal P-gp. In pharmacokinetic study, the absolute oral bioavailability of PTX loaded in hybrid liposomes had reached to 37.91%. All of these results demonstrated that the application of this novel PTX loaded hybrid liposomes is a strategy with great potential for highly effective oral PTX delivery.
Topics: Administration, Oral; Animals; Antineoplastic Agents, Phytogenic; Drug Delivery Systems; Drug Liberation; Humans; Intestinal Absorption; Liposomes; MCF-7 Cells; Male; Micelles; Paclitaxel; Poloxamer; Polyethyleneimine; Rats, Wistar; Sodium Cholate
PubMed: 29028605
DOI: 10.1016/j.colsurfb.2017.10.016 -
Journal of Oncology Pharmacy Practice :... Mar 2024Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in... (Review)
Review
PURPOSE
Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in water and high toxicity, resulting in low drug tolerance. These difficulties could be resolved by using suitable pharmacological carriers. Hence, it is essential to determine innovative methods of administering this effective medication to overcome paclitaxel's inherent limitations.
METHODS
An extensive literature search was conducted using multiple electronic databases to identify relevant studies published.
RESULTS
In this comprehensive analysis, many different paclitaxel delivery systems are covered and discussed, such as albumin-bound paclitaxel, polymeric micelles, paclitaxel-loaded liposomes, prodrugs, cyclodextrins, and peptide-taxane conjugates. Moreover, the review also covers various delivery routes of conventional paclitaxel or novel paclitaxel formulations, such as oral administration, local applications, and intraperitoneal delivery.
CONCLUSION
In addition to albumin-bound paclitaxel, polymeric micelles appear to be the most promising formulations for innovative drug delivery systems at present. A variety of variants of polymeric micelles are currently undergoing advanced phases of clinical trials.
Topics: Humans; Micelles; Antineoplastic Agents, Phytogenic; Albumin-Bound Paclitaxel; Paclitaxel; Drug Delivery Systems; Polymers; Drug Carriers
PubMed: 38204196
DOI: 10.1177/10781552231208978 -
Journal of Pharmacy & Pharmaceutical... 2006An important step in the development of liposome-based formulations is estimating the free drug concentration in the aqueous solution surrounding liposomes. This...
PURPOSE
An important step in the development of liposome-based formulations is estimating the free drug concentration in the aqueous solution surrounding liposomes. This research presents a new method for determination of free concentrations, based on membrane-protected solid-phase microextraction (SPME).
METHODS
For effective direct extraction of low molecular weight compounds from complex liquid samples, a hollow membrane was used to form a concentric sheath around a coated SPME fiber. The membrane blocked the access of large particles, like liposomes, to the coating surface, while target analytes with low molecular weight diffused through the membrane and reached the extraction phase. Quantification was conveniently performed by reversed-phase liquid chromatography coupled to electrospray ionization mass spectrometry.
RESULTS
The carbowax/templated resin SPME fiber was determined to be the most suitable for these assays, providing enough sensitivity when an extraction time of one hour was used. The free concentration of paclitaxel was found to be 0.36 microg/mL, significantly below the solubility limit of paclitaxel in water.
CONCLUSION
The method was successfully applied for determining free paclitaxel in liposome formulations based on dioleyl-trimethyl-ammonium-propane, with good linearity over the range of concentrations of interest. The method was faster and more practical than equilibrium dialysis, as the SPME approach provided preconcentration and convenient delivery to the analytical system.
Topics: Antineoplastic Agents; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Liposomes; Mass Spectrometry; Paclitaxel; Solubility
PubMed: 16959192
DOI: No ID Found -
Journal of Biomaterials Applications Sep 2015Conventional therapeutic approaches for cancer are limited by cancer cell resistance, which has impeded their clinical applications. The main goal of this work was to...
Conventional therapeutic approaches for cancer are limited by cancer cell resistance, which has impeded their clinical applications. The main goal of this work was to investigate the combined antitumor effect of paclitaxel with small interfering RNA modified by cationic liposome formed from modified octadecyl quaternized carboxymethyl chitosan. The cationic liposome was composed of 3β-[N-(N', N'-dimethylaminoethane)-carbamoyl]-cholesterol, dioleoylphosphatidylethanolamine, and octadecyl quaternized carboxymethyl chitosan. The cationic liposome properties were characterized by Fourier transform infrared spectroscopy, dynamic light scattering and zeta potential measurements, transmission electron microscopy, atomic force microscopy, and gel retardation assay. The cationic liposome exhibited good properties, such as a small particle size, a narrow particle size distribution, a good spherical shape, a smooth surface, and a good binding ability with small interfering RNA. Most importantly, when combined with paclitaxel and small interfering RNA, the composite cationic liposome induced a great enhancement in the antitumor activity, which showed a significantly higher in vitro cytotoxicity in Bcap-37 cells than liposomal paclitaxel or small interfering RNA alone. In conclusion, the results indicate that cationic liposome could be further developed as a codelivery system for chemotherapy drugs and therapeutic small interfering RNAs.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Cations; Chitosan; Drug Carriers; Liposomes; Microscopy, Atomic Force; Microscopy, Electron, Transmission; Neoplasms; Paclitaxel; RNA, Small Interfering; Spectroscopy, Fourier Transform Infrared
PubMed: 25838353
DOI: 10.1177/0885328215579297 -
International Journal of Nanomedicine 2018In this study, a novel arginine, glycine, aspartic acid peptide (RGD)-modified paclitaxel and curcumin co-loaded liposomes were developed to evaluate their antitumor...
PURPOSE
In this study, a novel arginine, glycine, aspartic acid peptide (RGD)-modified paclitaxel and curcumin co-loaded liposomes were developed to evaluate their antitumor activity in vitro and in vivo.
MATERIALS AND METHODS
Co-loaded liposomes were prepared using the solvent evaporation method. The particles had spherical shapes under electron microscopy with sizes <130 nm.
RESULTS
By comparison with the free drug, RGD-modified paclitaxel and curcumin co-loaded liposomes and paclitaxel and curcumin co-loaded liposomes have sustained-release properties in vitro. In vivo, there was no significant difference in pharmacokinetic parameters between the RGD-modified paclitaxel and curcumin co-loaded liposomes and paclitaxel and curcumin co-loaded liposomes. A strong green fluorescence was observed in the cytoplasmic region after incubation of RGD-modified paclitaxel and curcumin co-loaded liposomes for 2 h. RGD-modified paclitaxel and curcumin co-loaded liposomes showed a superior antiproliferative effect on A549 cells with a possible mechanism that suppressed the multidrug resistance phenomenon and exhibited a clear synergistic effect.
CONCLUSION
The results indicate that RGD-modified paclitaxel and curcumin co-loaded liposomes had a better antitumor effect in vivo than the non-modified LPs. These results indicate that RGD-modified co-loaded liposomes are a promising candidate for antitumor drug delivery.
Topics: Animals; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Curcumin; Drug Delivery Systems; Drug Liberation; Female; Humans; Liposomes; Lung Neoplasms; Male; Mice, Inbred BALB C; Oligopeptides; Paclitaxel; Rats, Sprague-Dawley; Xenograft Model Antitumor Assays
PubMed: 29731631
DOI: 10.2147/IJN.S157746