← Back to Search
Paclitaxel-loaded PLGA Nanoparticles: Preparation, Physicochemical Characterization And In Vitro Anti-tumoral Activity.
Cristina Fonseca, S. Simões, R. Gaspar
Published 2002 · Medicine, Chemistry
Download PDFAnalyze on Scholarcy
The main objective of this study was to develop a polymeric drug delivery system for paclitaxel, intended to be intravenously administered, capable of improving the therapeutic index of the drug and devoid of the adverse effects of Cremophor EL. To achieve this goal paclitaxel (Ptx)-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Ptx-PLGA-Nps) were prepared by the interfacial deposition method. The influence of different experimental parameters on the incorporation efficiency of paclitaxel in the nanoparticles was evaluated. Our results demonstrate that the incorporation efficiency of paclitaxel in nanoparticles was mostly affected by the method of preparation of the organic phase and also by the organic phase/aqueous phase ratio. Our data indicate that the methodology of preparation allowed the formation of spherical nanometric (<200 nm), homogeneous and negatively charged particles which are suitable for intravenous administration. The release behaviour of paclitaxel from the developed Nps exhibited a biphasic pattern characterised by an initial fast release during the first 24 h, followed by a slower and continuous release. The in vitro anti-tumoral activity of Ptx-PLGA-Nps developed in this work was assessed using a human small cell lung cancer cell line (NCI-H69 SCLC) and compared to the in vitro anti-tumoral activity of the commercial formulation Taxol. The influence of Cremophor EL on cell viability was also investigated. Exposure of NCI-H69 cells to 25 microg/ml Taxol resulted in a steep decrease in cell viability. Our results demonstrate that incorporation of Ptx in nanoparticles strongly enhances the cytotoxic effect of the drug as compared to Taxol, this effect being more relevant for prolonged incubation times.
This paper references
A new paren - developed in this work may be considered promising teral emulsion for the administration of Taxol
T. G. Sambandan Tarr (2001)
Novel Taxol Formulations: Preparation and Characterization of Taxol-Containing Liposomes
Amarnath Sharma (2004)
Rapid calorimetric assay for cellular growth 69. and survival: application of proliferation and cytotoxicity
anticancer drug paclitaxel (Taxol) Ann
Chemotherapy for advanced ovarian cancer: nanoparticles containing paclitaxel
J T Thigpen (2001)
Cell kill kinetics and cell cycle effects of taxol on human and hamster ovarian cell lines
N. M. Lopes (2004)
A Submicron Lipid Emulsion Coated with Amphipathic Polyethylene Glycol for Parenteral Administration of Paclitaxel (Taxol)
B. Lundberg (1997)
Metastatic breast cancer ery in cancer chemotherapy
T. P. Chelvi D. Sharma
Taxol: a new and effective anti-cancer drug.
W. Slichenmyer (1991)
Drug therapy: paclitaxel— biodegradable microspheres and nanospheres for the conreview article, New Engl
E K Rowinsky (1993)
Optimized preparation of poly(D,L lactic-co-gly- 1 (4) (1991) 221–241. colic) acid microspheres and nanospheres for oral
Pharmaceutical aspects of paclitaxel
R. Panchagnula (1998)
ylcyanoacrylate nanospheres against multidrug-resistant cells Dev
Journal of Controlled Release
C Fonseca (2002)
Solubility and stability of taxol: effects of buffers and cyclodextrins
S. Dordunoo (1996)
Clinical pharmacokinetics of doxorubicin in glycolic acid) for parenteral administration Lieberhepatoma patients after a single intravenous injection of free man Dosage Forms
A Rolland (1989)
vivo study of two types of long-circulating solid lipid
D B Chen (2001)
Cremophor EL release of paclitaxel ( Taxol ) loaded poly ( lactic - co - glycolic solvent for paclitaxel and toxicity
J. B. Mitchell
Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers.
D. Quintanar-Guerrero (1998)
systems for in vivo paclitaxel delivery
The influence of Cremophor EL on the cell cycle effects of paclitaxel (Taxol®) in human tumor cell lines
J. Liebmann (2004)
Preparations of biodegradable nanospheres of water-soluble and insoluble drugs with D, L-lactide/glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior.
T. Niwa (1993)
Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer.
C. Spencer (1994)
Development of biodegradable microspheres and nanospheres for the controlled release of cyclosporin A
A. Sánchez (1993)
increase of the drug concentration near its site of
Pharmacology and toxicology of Cremophor EL reproducible formation of nanometric (,200 nm), diluent
R T Dorr (1994)
Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation.
H. Gelderblom (2001)
Effects of prolonged versus short-term exposure paclitaxel (Taxol) on human tumor colony-forming units.
E. Raymond (1997)
Preparation and assay
Effects of emulsifiers on the con - liposomes in human small cell lung cancer , Biochim . Bio - trolled release of paclitaxel ( Taxol ) from nanospheres of phys
G. F. Huang Feng (2001)
The preparation of sub-200 nm biodegradable colloidal particles from poly(β-malic acid-co-benzyl malate) copolymers and their surface modification with Poloxamer and Poloxamine surfactants
S. Stolnik (1994)
In vitro and in vivo antitumoral activity of free, and encapsulated taxol.
M. H. Bartoli (1990)
Effects of for targeted delivery of a novel anticancer agent, Taxol, prolonged versus short-term exposure paclitaxel (taxol) on human tumor colony-forming units
E Raymond (1996)
Weekly paclitaxel in advanced non-small cell lung cancer.
A. Chang (2001)
Int. J. Pharm
H Fessi (1996)
would favour a drug influx into the cell [ 62 ] ; ( ii ) Weekly paclitaxel in advanced non - small cell lung cancer , tumoral cells ( which in many situations exhibited Semin
J. Rubins Chang
Influence of cationic lipids on the stability and membrane properties of paclitaxel-containing liposomes.
R. Campbell (2001)
ultra-dispersed polymer systems Speiser, Tissue distribution of antitumor drugs associated
P Couvreur (1991)
results, it can be concluded that the formulations
Enhanced Preparation techniques and mechanisms of formation of cytotoxicity of doxorubicin encapsulated in polyisohexbiodegradable nanoparticles from preformed polymers
In vitro and in vivo study of two types of long-circulating solid lipid nanoparticles containing paclitaxel.
D. Chen (2001)
Influence of Surface Properties at Biodegradable Microsphere Surfaces: Effects on Plasma Protein Adsorption and Phagocytosis
F. Lacasse (2004)
In vitro and in vivo evaluation of taxol release from poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate and degradation of the microspheres
Y. Wang (1997)
Les polymères à base d'acides lactiques et glycolique et la délivrance contrôlée des principes actifs
J. Mauduit (1993)
Polymeric dispersions as drug
Augmentation vent - and Concentration - dependent molecular interactions of of transvascular transport of macromolecules and nanoparti - Taxol ( Paclitaxel )
Paclitaxel — a review of its pharma - meric nanoparticles allowing the drug to be released codynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer
The use of drug-loaded
W J Slichenmyer
Pharmaceutical Dosage Forms: Disperse Systems
H. Lieberman (1988)
The results obtained showed that the methodology diluted in infusion solutions and stored in various containers, selected in this work allowed the instantaneous and Am
J Liebmann (2001)
Metastatic breast cancer with resistance to both anthracycline and docetaxel successfully treated with weekly paclitaxel
M. Ishitobi (2001)
Prolonged controlled-release of nafarelin, a luteinizing hormone-releasing hormone analogue, from biodegradable polymeric implants: influence of composition and molecular weight of polymer.
L. M. Sanders (1986)
Nanocapsule formation by interfacial polymer deposition following solvent displacement
H. Fessi (1989)
biodegradable microspheres surfaces: effects on plasma
Enhanced cytotoxicity of doxorubicin encapsulated in polyisohexylcyanoacrylate nanospheres against multidrug-resistant tumour cells in culture.
S. Bennis (1994)
Colloidal Drug Delivery Systems
J. Kreuter (1994)
Polymeric Dispersions as Drug Carriers
R. Bodmeier (1998)
Optimized preparation of poly d,l (lactic-glycolic) microspheres and nanoparticles for oral administration
M. Chacón (1996)
Solvent- and concentration-dependent molecular interactions of taxol (Paclitaxel).
S. V. Balasubramanian (1994)
Chemotherapy for advanced ovarian cancer: overview of randomized trials.
J. Thigpen (2000)
Nanoparticle characterization : a comprehensive physicochemical approach
B. Magenheim (1991)
enhanced endocytotic activity) can internalise
Cell kill protein adsorption and phagocytosis kinetics and cell cycle effects of taxol on human and hamster
M Lopes (1998)
Cell cultures for the assessment of toxicity and uptake of polymeric particulate drug carriers
S. Maassen (1993)
Hydrophobic collapse of taxol and taxotere solution conformations in mixtures of water and organic solvent
D. V. Velde (1993)
Nanospheres of biodegradable polymers: a system for clinical administration of an anticancer drug paclitaxel (Taxol).
S. Feng (2000)
Effects of emulsifiers on the conliposomes in human small cell lung cancer, Biochim. Biotrolled release of paclitaxel (Taxol) from nanospheres of phys
S S Feng (2001)
Paclitaxel—a review of its pharmameric nanoparticles allowing the drug to be released codynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer
A new parendeveloped in this work may be considered promising teral emulsion for the administration of Taxol
B D Tarr (1987)
Influence of surface properties
F X Lacasse (1997)
C Vauthier-Holtzsherer (2001)
Drug therapy : paclitaxel (Taxol)
E. Rowinsky (1995)
Cell kill protein adsorption and phagocytosis
P. Hildgen McMullen (1997)
Paclitaxel loaded poly(L-lactic acid) microspheres: properties of microspheres made with low molecular weight polymers.
R. Liggins (2001)
Cremophor EL, solvent for paclitaxel, and toxicity
J. Liebmann (1993)
J.P. De- Technology Foundation
M H Bartoli
Hypersensitivity reactions from taxol.
R. Weiss (1990)
Pharmacology and Toxicology of Cremophor EL Diluent
R. Dorr (1994)
Maria Jose Alonso
Pharmacology and toxicology of Cremophor ELreproducible formation of nanometric ( , 200 nm ) , diluent
V. J. Stella
Novel Taxol formulation: polyvinylpyrrolidone nanoparticle-encapsulated Taxol for drug delivery in cancer therapy.
D. Sharma (1996)
PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug.
T. Govender (1999)
The use of drug-loaded nanoparticles in cancer chemotherapy
J. Leroux (1996)
H Sato (1997)
its anti - tumoral efficacy as compared to the free drug Cremophor EL : the drawbacks and advantages of vehicle ( Taxol ) , this effect being more relevant for pro - selection for drug formulation
J. Verweij Gelderblom
Clinical pharmacokinetics of doxorubicin in hepatoma patients after a single intravenous injection of free or nanoparticle-bound anthracycline
A. Rolland (1989)
nanoparticles of poly(lactic acid) and poly(lactic
E Alleman (1980)
A growth pore
J N Moreira (2000)
A growth factor antagonist as a targeting agent for sterically stabilized liposomes in human small cell lung cancer.
J. Moreira (2001)
Pharmacokinetic study of taxol-loaded poly(lactic-co-glycolic acid) microspheres containing isopropyl myristate after targeted delivery to the lung in mice.
H. Sato (1996)
would favour a drug influx into the cell ; (ii) Weekly paclitaxel in advanced non-small cell lung cancer, tumoral cells (which in many situations exhibited
A Y Chang (2001)
Effects of for targeted delivery of a novel anticancer agent , Taxol , prolonged versus short - term exposure paclitaxel ( taxol ) on Chem
A. Hanauske Raymond
Metastatic breast cancer ery in cancer chemotherapy, Oncol
M. Ishitobi (1996)
Stability, compatibility, and plasticizer extraction of taxol (NSC-125973) injection diluted in infusion solutions and stored in various containers.
W. Waugh (1991)
A New Parenteral Emulsion for the Administration of Taxol
B. Tarr (2004)
Fabrication, characterization and in vitro release of paclitaxel (Taxol) loaded poly (lactic-co-glycolic acid) microspheres prepared by spray drying technique with lipid/cholesterol emulsifiers.
L. Mu (2001)
Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
T. Mosmann (1983)
In vitro and in vivovivó vivóˆvivóˆ´ et glycolique at la delivrance controlee des principes actifs, evaluation of taxol release from poly(lactic-co-glycolic acid) STP Pharma Sci
M Wang (1993)
Cell cultures sition following solvent displacement1) for the assessment of toxicity and uptake of polymeric
S Maaben (1989)
fully treated with weakly paclitaxel
Drug therapy : paclitaxel — biodegradable microspheres and nanospheres for the con - review article , New Engl
R. C. Donehower Rowinsky
Surface modification of i.v. injectable biodegradable nanoparticles with poloxamer polymers and poloxamine 908
R. Mueller (1993)
L Marshal-Heussler (1993)
Microencapsulation : methods and industrial applications
S. Benita (1996)
macokinetic study of taxol-loaded poly(lactic-co-glycolic
Surface modification of i.v. carriers Banker injectable biodegradable nanoparticles with poloxamer poly Pharmaceutical Dosage Forms: Disperse Systems, mers and poloxamine 908
R H Muller (1993)
Cytotoxic studies of paclitaxel (Taxol) in human tumour cell lines.
J. Liebmann (1993)
Effects of emulsifiers on the controlled release of paclitaxel (Taxol) from nanospheres of biodegradable polymers.
S. Feng (2001)
Preparation and characterization of poly(lactic-co-glycolic acid) microspheres for targeted delivery of a novel anticancer agent, taxol.
Y. Wang (1996)
In vitro and in vivo ́ ˆ ́ et glycolique at la delivrance controlee des principes actifs , evaluation of taxol release from poly ( lactic - co - glycolic acid )
H. Sato (1993)
Nanospheres of biodegradable polymers: a system for clinical administration of an patibility of PLA and PLGA microspheres
S S Feng (1997)
Methodology for the preparation of
Augmentation vent-and Concentration-dependent molecular interactions of of transvascular transport of macromolecules and nanoparti- Taxol (Paclitaxel)
W L Monsky (1476)
Novel taxol formulations: preparation and characterization of Taxol containing lipo- The authors would like to acknowledge Professor somes
A Sharma (1994)
Tissue distribution of antitumor drugs associated with polyalkylcyanoacrylate nanoparticles.
P. Couvreur (1980)
Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study.
J. Szebeni (1998)
Some parameters influencing cytotoxicity of free doxorubicin and doxorubicin-loaded nanoparticles in sensitive and multidrug resistant leucemic murine cells: incubation time, number of nanoparticles per cell
F. Nemati (1994)
Formulation of L-asparaginase-loaded poly(lactide-co-glycolide) nanoparticles: influence of polymer properties on enzyme loading, activity and in vitro release.
M. M. Gasper (1998)
Metastatic breast cancer ery in cancer chemotherapy1996) with resistance to both anthracycline and docetaxel success
Paclitaxel loaded poly(L-lactic cycle effects of paclitaxel (Taxol) in human tumor cell lines, acid) microspheres: properties of microspheres made with
R T Liggins (1994)
Solubility and stability of taxol: loading and release studies of a water soluble drug, J. effects of buffers and cyclodextrins
S K Dordunoo (1996)
acid) microspheres containing isopropyl myristate after J.B. Mitchell, Cytotoxic studies of paclitaxel (Taxol) in targeted delivery to the lung in mice
J Liebmann (1993)
Hyper - sensitivity reactions from Taxol
P. H. Wiernik
Augmentation of transvascular transport of macromolecules and nanoparticles in tumors using vascular endothelial growth factor.
W. Monsky (1999)
Biodegradation and biocompatibility of PLA and PLGA microspheres.
Preparation, characterization and properties of sterically stabilized paclitaxel-containing liposomes.
P. Crosasso (2000)
spherical and homogeneous PLGA nanoparticles that
井口 泰泉 (1986)
This paper is referenced by
Design and Synthesis of New Sulfur-Containing Hyperbranched Polymer and Theranostic Nanomaterials for Bimodal Imaging and Treatment of Cancer.
Blaze Heckert (2017)
Nanoparticle and targeted systems for cancer therapy.
L. Brannon-Peppas (2004)
Development and validation of a fluorimetric method to determine curcumin in lipid and polymeric nanocapsule suspensions
L. Mazzarino (2010)
Nano Technology in Medicine and Future Implications: A Mini Review
K. A. Wani (2018)
Nanoparticle-Based Manipulation of Antigen-Presenting Cells for Cancer Immunotherapy.
R. Fang (2015)
Pulmonary applications and toxicity of engineered nanoparticles.
J. W. Card (2008)
Advanced biomaterials for cancer immunotherapy
F. Yang (2020)
Anti-cancer nanoparticulate drug delivery system using biodegradable polymers
Harish Gopinath (2013)
Evaluation of polymeric PLGA nanoparticles conjugated to curcumin for use in aPDT
Renata Celi Carvalho de Souza Pietra (2017)
Lipid shell modified with combination of lipid and phospholipids in solid lipid nanoparticles for engineered specificity of paclitaxel in tumor bearing mice.
Sidharth Malgounda Patil (2013)
Paclitaxel: a review of adverse toxicities and novel delivery strategies
Neena I. Marupudi (2007)
Poly(lactide-co-glycolide) nanoparticles as carriers for norcantharidin
Q. Zeng (2009)
A robust systematic design: Optimization and preparation of polymeric nanoparticles of PLGA for docetaxel intravenous delivery.
Pedram Rafiei (2019)
Purified and surfactant-free coenzyme Q10-loaded biodegradable nanoparticles.
B. J. Nehilla (2008)
Paclitaxel loading in PLGA nanospheres affected the in vitro drug cell accumulation and antiproliferative activity
L. Vicari (2008)
Chlorambucil Encapsulation into PLGA Nanoparticles and Cytotoxic Effects in Breast Cancer Cell
Diego Juscelino Santos Dias (2015)
Biodegradable Nanoparticles and Their In Vivo Fate
A. Kumari (2016)
Efficient inhibition of intraperitoneal human ovarian cancer growth by short hairpin RNA targeting CD44.
Li-juan Zou (2014)
Taxane Formulations: From Plant to Clinic
Abdelbary M. A. Elhissi (2018)
Biodegradable Polymers - A Review
K. Vasanthi (2017)
Assessment of intestinal permeability of paclitaxel in the presence of NSAIDs and P-glycoprotein inhibitors
Zahra Sobhani (2017)
DETERMINATION OF PACLITAXEL BY 3D VIEW LC-DIODE ARRAY UV: ITS APPLICATION TO AN IN SITU CLOSED LOOP RE-CIRCULATING INTESTINE ABSORPTION STUDY IN RATS
Sekar Vasanthakumar (2013)
Clinical developments of antitumor polymer therapeutics
S. Parveen (2019)
In vitro and in vivo evaluation of docetaxel-loaded stearic acid-modified Bletilla striata polysaccharide copolymer micelles
Qingxiang Guan (2017)
The characterization of paclitaxel-loaded microspheres manufactured from blends of poly(lactic-co-glycolic acid) (PLGA) and low molecular weight diblock copolymers.
J. Jackson (2007)
Multifunctional biodegradable polyacrylamide nanocarriers for cancer theranostics--a "see and treat" strategy.
Shouyan Wang (2012)
Glycyrrhetinic acid-graft-hyaluronic acid conjugate as a carrier for synergistic targeted delivery of antitumor drugs.
L. Zhang (2013)
Paclitaxel-loaded PLGA nanoparticles surface modified with transferrin and Pluronic®P85, an in vitro cell line and in vivo biodistribution studies on rat model
N. Shah (2009)
Multicellular Tumor Spheroids for Evaluation of Cytotoxicity and Tumor Growth Inhibitory Effects of Nanomedicines In Vitro: A Comparison of Docetaxel-Loaded Block Copolymer Micelles and Taxotere®
A. Mikhail (2013)
Tocol emulsions for drug solubilization and parenteral delivery.
P. Constantinides (2004)
Programmed Hydrolysis in Designing Paclitaxel Prodrug for Nanocarrier Assembly
Q. Fu (2015)
Surface-modified gatifloxacin nanoparticles with potential for treating central nervous system tuberculosis
P. Marcianes (2017)See more