Pharmacokinetics and in vivo drug release rates in liposomal nanocarrier development.

Liposomes represent a widely varied and malleable class of drug carriers generally characterized by the presence of one or more amphiphile bilayers enclosing an interior aqueous space. Thus, the pharmacological profile of a particular liposomal drug formulation is a function not only of the properties of the encapsulated drug, but to a significant extent of the pharmacokinetics, biodistribution, and drug release rates of the individual carrier. Various physicochemical properties of the liposomal carriers, the drug encapsulation and retention strategies utilized, and the properties of the drugs chosen for encapsulation, all play an important role in determining the effectiveness of a particular liposomal drug. These properties should be carefully tailored to the specific drug, and to the application for which the therapeutic is being designed. Liposomal carriers are also amenable to additional modifications, including the conjugation of targeting ligands or environment-sensitive triggers for increasing the bioavailability of the drug specifically at the site of disease. This review describes the rationale for selecting optimal strategies of liposomal drug formulations with respect to drug encapsulation, retention, and release, and how these strategies can be applied to maximize therapeutic benefit in vivo.

[1]  D. Lasič,et al.  Liposomes: From Physics to Applications , 1993 .

[2]  A. Chanan-Khan,et al.  Bortezomib in combination with pegylated liposomal doxorubicin for the treatment of multiple myeloma. , 2007, Clinical lymphoma & myeloma.

[3]  M. Dewhirst,et al.  Efficacy of liposomes and hyperthermia in a human tumor xenograft model: importance of triggered drug release. , 2000, Cancer research.

[4]  M. Bally,et al.  Influence of pH gradients on the transbilayer transport of drugs, lipids, peptides and metal ions into large unilamellar vesicles. , 1997, Biochimica et biophysica acta.

[5]  W. Hong,et al.  Phase II study of a liposome-entrapped cisplatin analog (L-NDDP) administered intrapleurally and pathologic response rates in patients with malignant pleural mesothelioma. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  L. Keus,et al.  Feasibility, Phase I, and Pharmacological Study of Aerosolized Liposomal 9‐Nitro‐20(S)‐Camptothecin in Patients with Advanced Malignancies in the Lungs , 2000 .

[7]  M. Bally,et al.  Ratiometric dosing of anticancer drug combinations: Controlling drug ratios after systemic administration regulates therapeutic activity in tumor-bearing mice , 2006, Molecular Cancer Therapeutics.

[8]  A. Janoff,et al.  Activity of paclitaxel liposome formulations against human ovarian tumor xenografts , 1997, International journal of cancer.

[9]  M. Zignani,et al.  Current status of pH-sensitive liposomes in drug delivery. , 2000, Progress in lipid research.

[10]  Theresa M Allen,et al.  Drug release rate influences the pharmacokinetics, biodistribution, therapeutic activity, and toxicity of pegylated liposomal doxorubicin formulations in murine breast cancer. , 2004, Biochimica et biophysica acta.

[11]  T. Sonobe,et al.  Liposomalization of SN-38 as active metabolite of CPT-11. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[12]  M. Bally,et al.  The presence of GM1 in liposomes with entrapped doxorubicin does not prevent RES blockade. , 1993, Biochimica et biophysica acta.

[13]  T. Chen,et al.  Alkylated derivatives of poly(ethylacrylic acid) can be inserted into preformed liposomes and trigger pH-dependent intracellular delivery of liposomal contents , 2004, Molecular membrane biology.

[14]  K. Edwards,et al.  An evaluation of transmembrane ion gradient-mediated encapsulation of topotecan within liposomes. , 2004, Journal of controlled release : official journal of the Controlled Release Society.

[15]  F. Szoka,et al.  Cholesterol phosphate derivatives: synthesis and incorporation into a phosphatase and calcium-sensitive triggered release liposome. , 1998, Bioconjugate chemistry.

[16]  D. Tzemach,et al.  Comparative study of the antitumor activity of free doxorubicin and polyethylene glycol-coated liposomal doxorubicin in a mouse lymphoma model. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[17]  A. Malik,et al.  Regulation of vascular endothelial barrier function. , 1994, The American journal of physiology.

[18]  P. Cullis,et al.  The bilayer stabilizing role of sphingomyelin in the presence of cholesterol: a 31P NMR study. , 1980, Biochimica et biophysica acta.

[19]  Anitha Thomas,et al.  Transition Metal-Mediated Liposomal Encapsulation of Irinotecan (CPT-11) Stabilizes the Drug in the Therapeutically Active Lactone Conformation , 2006, Pharmaceutical Research.

[20]  Joel A Swanson,et al.  Drug delivery strategy utilizing conjugation via reversible disulfide linkages: role and site of cellular reducing activities. , 2003, Advanced drug delivery reviews.

[21]  M. Bally,et al.  Improved retention of idarubicin after intravenous injection obtained for cholesterol-free liposomes. , 2002, Biochimica et biophysica acta.

[22]  Uchiyama,et al.  The size of liposomes: a factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs. , 1999, Advanced drug delivery reviews.

[23]  M. Bally,et al.  The formulation of lipid-based nanotechnologies for the delivery of fixed dose anticancer drug combinations. , 2005, Current drug delivery.

[24]  Samuel Zalipsky,et al.  Liposomes with detachable polymer coating: destabilization and fusion of dioleoylphosphatidylethanolamine vesicles triggered by cleavage of surface‐grafted poly(ethylene glycol) , 1996, FEBS letters.

[25]  F. Szoka,et al.  Chemical approaches to triggerable lipid vesicles for drug and gene delivery. , 2003, Accounts of chemical research.

[26]  G. Scambia,et al.  Pegylated liposomal doxorubicin-related palmar-plantar erythrodysesthesia ('hand-foot' syndrome). , 2007, Annals of oncology : official journal of the European Society for Medical Oncology.

[27]  A. Judge,et al.  Hypersensitivity and loss of disease site targeting caused by antibody responses to PEGylated liposomes. , 2006, Molecular therapy : the journal of the American Society of Gene Therapy.

[28]  M. Bally,et al.  A Comparison of Liposomal Formulations of Doxorubicin with Drug Administered in Free Form , 2001, Drug safety.

[29]  Michael Hawkins,et al.  Comparative Preclinical and Clinical Pharmacokinetics of a Cremophor-Free, Nanoparticle Albumin-Bound Paclitaxel (ABI-007) and Paclitaxel Formulated in Cremophor (Taxol) , 2005, Clinical Cancer Research.

[30]  K. Kono,et al.  Thermosensitive polymer-modified liposomes. , 2001, Advanced drug delivery reviews.

[31]  L. Leserman,et al.  Immune clearance of liposomes inhibited by an anti-Fc receptor antibody in vivo. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[32]  F. Szoka,et al.  Low‐pH‐sensitive poly(ethylene glycol) (PEG)‐stabilized plasmid nanolipoparticles: effects of PEG chain length, lipid composition and assembly conditions on gene delivery , 2005, The journal of gene medicine.

[33]  M. Yatvin,et al.  pH-sensitive liposomes: possible clinical implications. , 1980, Science.

[34]  R K Jain,et al.  Transport in lymphatic capillaries. I. Macroscopic measurements using residence time distribution theory. , 1996, The American journal of physiology.

[35]  R. B. Campbell,et al.  Influence of cationic lipids on the stability and membrane properties of paclitaxel-containing liposomes. , 2001, Journal of pharmaceutical sciences.

[36]  F. Muggia,et al.  Pegylated liposomal doxorubicin HCL (PLD; Caelyx/Doxil): experience with long-term maintenance in responding patients with recurrent epithelial ovarian cancer. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[37]  R. Straubinger,et al.  Pharmacokinetics of paclitaxel-containing liposomes in rats , 2003, AAPS PharmSci.

[38]  Simon C Watkins,et al.  Dynamic changes in the characteristics of cationic lipidic vectors after exposure to mouse serum: implications for intravenous lipofection , 1999, Gene Therapy.

[39]  D. Alberts,et al.  Role of pegylated liposomal doxorubicin in ovarian cancer. , 2005, Gynecologic oncology.

[40]  N. Harbeck,et al.  Reduced Incidence of Severe Palmar-Plantar Erythrodysesthesia and Mucositis in a Prospective Multicenter Phase II Trial with Pegylated Liposomal Doxorubicin at 40 mg/m2 Every 4 Weeks in Previously Treated Patients with Metastatic Breast Cancer , 2006, Oncology.

[41]  Corrie Lynn Messerer,et al.  Liposomal Irinotecan , 2004, Clinical Cancer Research.

[42]  F. Szoka,et al.  Distribution in brain of liposomes after convection enhanced delivery; modulation by particle charge, particle diameter, and presence of steric coating , 2005, Brain Research.

[43]  M. Dewhirst,et al.  Preferential extravasation and accumulation of liposomal vincristine in tumor comparing to normal tissue enhances antitumor activity , 2006, Cancer Chemotherapy and Pharmacology.

[44]  D. Papahadjopoulos,et al.  Permeability properties of phospholipid membranes: effect of cholesterol and temperature. , 1972, Biochimica et biophysica acta.

[45]  M. Bally,et al.  Characterization of liposomal systems containing doxorubicin entrapped in response to pH gradients. , 1990, Biochimica et biophysica acta.

[46]  G. Scherphof,et al.  UPTAKE AND PROCESSING OF IMMUNOGLOBULIN-COATED LIPOSOMES BY SUBPOPULATIONS OF RAT-LIVER MACROPHAGES , 1988 .

[47]  R. Straubinger,et al.  Paclitaxel-liposomes for intracavitary therapy of intraperitoneal P388 leukemia. , 1996, Cancer letters.

[48]  L. Huang,et al.  Structural and functional comparisons of pH-sensitive liposomes composed of phosphatidylethanolamine and three different diacylsuccinylglycerols. , 1990, Biochimica et biophysica acta.

[49]  Ulrik B Nielsen,et al.  Anti-HER2 immunoliposomes: enhanced efficacy attributable to targeted delivery. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.

[50]  M. Bally,et al.  The accumulation of drugs within large unilamellar vesicles exhibiting a proton gradient: a survey. , 1990, Chemistry and physics of lipids.

[51]  T. Allen,et al.  Immune cell-mediated antitumor activities of GD2-targeted liposomal c-myb antisense oligonucleotides containing CpG motifs. , 2004, Journal of the National Cancer Institute.

[52]  Yu Zhou,et al.  Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. , 2007, Journal of molecular biology.

[53]  A. Tall,et al.  Interaction between unilamellar egg yolk lecithin vesicles and human high density lipoprotein. , 1979, Biochemistry.

[54]  W. Guo,et al.  A simple and sensitive LC/MS/MS assay for 7-ethyl-10-hydroxycamptothecin (SN-38) in mouse plasma and tissues: application to pharmacokinetic study of liposome entrapped SN-38 (LE-SN38). , 2005, Journal of pharmaceutical and biomedical analysis.

[55]  P. Cullis,et al.  Anomalous solubility behavior of the antibiotic ciprofloxacin encapsulated in liposomes: a 1H-NMR study. , 1998, Biochimica et biophysica acta.

[56]  D. Stuart,et al.  A new liposomal formulation for antisense oligodeoxynucleotides with small size, high incorporation efficiency and good stability. , 2000, Biochimica et biophysica acta.

[57]  T. Ishida,et al.  Anti-PEG IgM elicited by injection of liposomes is involved in the enhanced blood clearance of a subsequent dose of PEGylated liposomes. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[58]  T. Ishida,et al.  Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[59]  Xiao-ling Fang,et al.  Biodistribution in mice and severity of damage in rat lungs following pulmonary delivery of 9-nitrocamptothecin liposomes. , 2008, Pulmonary pharmacology & therapeutics.

[60]  S. Kennel,et al.  Characterization of organ-specific immunoliposomes for delivery of 3′,5′-O-dipalmitoyl-5-fluoro-2′-deoxyuridine in a mouse lung-metastasis model , 2004, Cancer Chemotherapy and Pharmacology.

[61]  T M Allen,et al.  Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. , 1991, Biochimica et biophysica acta.

[62]  F M Muggia,et al.  Complement activation by Cremophor EL as a possible contributor to hypersensitivity to paclitaxel: an in vitro study. , 1998, Journal of the National Cancer Institute.

[63]  F. Martin,et al.  Arrest of human lung tumor xenograft growth in severe combined immunodeficient mice using doxorubicin encapsulated in sterically stabilized liposomes. , 1993, Cancer research.

[64]  J. Slotte,et al.  Membrane properties of D-erythro-N-acyl sphingomyelins and their corresponding dihydro species. , 2001, Biophysical journal.

[65]  R K Jain,et al.  Noninvasive measurement of interstitial pH profiles in normal and neoplastic tissue using fluorescence ratio imaging microscopy. , 1994, Cancer research.

[66]  D. Liggitt,et al.  Lipid-DNA complexes induce potent activation of innate immune responses and antitumor activity when administered intravenously. , 1999, Journal of immunology.

[67]  R. Jain,et al.  Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. , 1994, Cancer research.

[68]  D. Borchman,et al.  Conformational studies of sphingolipids by NMR spectroscopy , 2000 .

[69]  M. Bally,et al.  Copper-topotecan complexation mediates drug accumulation into liposomes. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[70]  C. Benz,et al.  Enhanced Pharmacodynamic and Antitumor Properties of a Histone Deacetylase Inhibitor Encapsulated in Liposomes or ErbB2-Targeted Immunoliposomes , 2005, Clinical Cancer Research.

[71]  T. Allen,et al.  Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues. , 1989, Biochimica et biophysica acta.

[72]  G. Schwartz,et al.  Phase I trial of dose-intense liposome-encapsulated doxorubicin in patients with advanced sarcoma. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[73]  C. Benz,et al.  Development of ligand-targeted liposomes for cancer therapy , 2004, Expert opinion on therapeutic targets.

[74]  D. Ribatti,et al.  Vascular damage and anti-angiogenic effects of tumor vessel-targeted liposomal chemotherapy. , 2003, Cancer research.

[75]  M. Dewhirst,et al.  Thermosensitive liposomes: extravasation and release of contents in tumor microvascular networks. , 1996, International journal of radiation oncology, biology, physics.

[76]  V. Grégoire,et al.  Modulation of the tumor vasculature functionality by ionizing radiation accounts for tumor radiosensitization and promotes gene delivery , 2002, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[77]  Susan O'Brien,et al.  Phase II study of sphingosomal vincristine in patients with recurrent or refractory adult acute lymphocytic leukemia , 2006, Cancer.

[78]  Jennifer I. Hare,et al.  Pharmacokinetics and pharmacodynamics of lipidic nano-particles in cancer. , 2006, Anti-cancer agents in medicinal chemistry.

[79]  Kamps,et al.  Receptor versus non-receptor mediated clearance of liposomes. , 1998, Advanced drug delivery reviews.

[80]  Yechezkel Barenholz,et al.  Prolongation of the Circulation Time of Doxorubicin Encapsulated in Liposomes Containing a Polyethylene Glycol-Derivatized Phospholipid: Pharmacokinetic Studies in Rodents and Dogs , 1993, Pharmaceutical Research.

[81]  F. Dosio,et al.  Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing docetaxel. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[82]  D. Colagiovanni,et al.  Pharmacokinetics , Safety , and Efficacy of a Liposome Encapsulated Thymidylate Synthase Inhibitor , OSI-7904 L [ ( S )-2-[ 5-[ ( 1 , 2-Dihydro-3-methyl-1-oxobenzo [ f ] quinazolin-9-yl ) methyl ] amino-1-oxo-2-isoindolynl ]-glutaric Acid ] in Mice , 2004 .

[83]  D. Tzemach,et al.  Long-circulating liposomes for drug delivery in cancer therapy: a review of biodistribution studies in tumor-bearing animals , 1997 .

[84]  W. Hong,et al.  Phase I clinical and pharmacological study of liposome-entrapped NDDP administered intrapleurally in patients with malignant pleural effusions. , 1997, Clinical cancer research : an official journal of the American Association for Cancer Research.

[85]  R. Perez-soler,et al.  In vivo antitumor activity of cis-bis-neodecanoato-trans- R,R-l,2-diaminocyclohexane platinum(II) formulated in long-circulating liposomes , 2009, Cancer Chemotherapy and Pharmacology.

[86]  M. Bally,et al.  Influence of vesicle size, lipid composition, and drug-to-lipid ratio on the biological activity of liposomal doxorubicin in mice. , 1989, Cancer research.

[87]  M. Bally,et al.  Studies on the myelosuppressive activity of doxorubicin entrapped in liposomes , 2004, Cancer Chemotherapy and Pharmacology.

[88]  L. Gianni,et al.  Anthracyclines: Molecular Advances and Pharmacologic Developments in Antitumor Activity and Cardiotoxicity , 2004, Pharmacological Reviews.

[89]  F. Muggia,et al.  Phase III data on Caelyx in ovarian cancer. , 2001, European journal of cancer.

[90]  S. Stewart,et al.  Randomized comparative trial of pegylated liposomal doxorubicin versus bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[91]  R. Straubinger,et al.  Novel Taxol Formulations: Preparation and Characterization of Taxol-Containing Liposomes , 1994, Pharmaceutical Research.

[92]  J. Schellens,et al.  Phase I and pharmacokinetic study of SPI-77, a liposomal encapsulated dosage form of cisplatin , 2002, Cancer Chemotherapy and Pharmacology.

[93]  L. Matherly,et al.  Human reduced folate carrier: translation of basic biology to cancer etiology and therapy , 2007, Cancer and Metastasis Reviews.

[94]  Xin Huang,et al.  A Bacterial Protein Enhances the Release and Efficacy of Liposomal Cancer Drugs , 2006, Science.

[95]  T. Fleming,et al.  Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. , 2001, The New England journal of medicine.

[96]  P. Cullis,et al.  Stabilized Plasmid–Lipid Particles: Pharmacokinetics and Plasmid Delivery to Distal Tumors following Intravenous Injection , 2000, Journal of drug targeting.

[97]  F. Martin,et al.  Doxorubicin encapsulated in sterically stabilized liposomes is superior to free drug or drug-containing conventional liposomes at suppressing growth and metastases of human lung tumor xenografts. , 1996, Cancer Research.

[98]  M. Bally,et al.  Kupffer cells do not play a role in governing the efficacy of liposomal mitoxantrone used to treat a tumor model designed to assess drug delivery to liver. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[99]  A. Bedikian,et al.  Pharmacokinetics and Urinary Excretion of Vincristine Sulfate Liposomes Injection in Metastatic Melanoma Patients , 2006, Journal of clinical pharmacology.

[100]  P. van Hoogevest,et al.  Transfer of lipophilic drugs between liposomal membranes and biological interfaces: consequences for drug delivery. , 2005, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[101]  S. Simões,et al.  Sterically stabilized ph-sensitive liposomes. , 2004, Methods in enzymology.

[102]  P. Meers,et al.  Enzyme-activated targeting of liposomes. , 2001, Advanced drug delivery reviews.

[103]  Y. Barenholz,et al.  Comparative long-term study of the toxicities of free and liposome-associated doxorubicin in mice after intravenous administration. , 1986, Journal of the National Cancer Institute.

[104]  Theresa M Allen,et al.  Internalizing antibodies are necessary for improved therapeutic efficacy of antibody-targeted liposomal drugs. , 2002, Cancer research.

[105]  Xin Yu Wang,et al.  Accelerated blood clearance of PEGylated liposomes following preceding liposome injection: effects of lipid dose and PEG surface-density and chain length of the first-dose liposomes. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[106]  T M Allen,et al.  Liver pathology accompanying chronic liposome administration in mouse. , 1985, Research communications in chemical pathology and pharmacology.

[107]  David H. Thompson,et al.  Cytosolic drug delivery using pH- and light-sensitive liposomes. , 1999, Advanced drug delivery reviews.

[108]  D. Baccanari,et al.  Antitumor efficacy, pharmacokinetics, and biodistribution of NX 211: a low-clearance liposomal formulation of lurtotecan. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[109]  Y. Barenholz,et al.  Characterization of sterically stabilized cisplatin liposomes by nuclear magnetic resonance. , 2001, Biochimica et biophysica acta.

[110]  M. Johnston,et al.  Therapeutically optimized rates of drug release can be achieved by varying the drug-to-lipid ratio in liposomal vincristine formulations. , 2006, Biochimica et biophysica acta.

[111]  A. Gabizon,et al.  Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies. , 1990, Cancer research.

[112]  B. Bondurant,et al.  Rapid release of liposomal contents upon photoinitiated destabilization with UV exposure. , 2003, Biochimica et biophysica acta.

[113]  Y. Assaraf The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis. , 2006, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[114]  D. Carbonaro,et al.  Preclinical safety, pharmacokinetics and antitumor efficacy profile of liposome-entrapped SN-38 formulation. , 2005, Anticancer research.

[115]  S. Simões,et al.  Sterically Stabilized pH-sensitive Liposomes , 1997, The Journal of Biological Chemistry.

[116]  F. Szoka,et al.  Thiocholesterol-based lipids for ordered assembly of bioresponsive gene carriers. , 2005, Molecular therapy : the journal of the American Society of Gene Therapy.

[117]  M S Newman,et al.  Immunogenicity and pharmacokinetic attributes of poly(ethylene glycol)-grafted immunoliposomes. , 1997, Biochimica et biophysica acta.

[118]  M. Hope,et al.  Immune stimulation by a CpG-containing oligodeoxynucleotide is enhanced when encapsulated and delivered in lipid particles. , 2001, The Journal of pharmacology and experimental therapeutics.

[119]  M. Newman,et al.  Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long-circulating, pegylated liposomes (SPI-077) in tumor-bearing mice , 1999, Cancer Chemotherapy and Pharmacology.

[120]  M. Bally,et al.  Uptake of antineoplastic agents into large unilamellar vesicles in response to a membrane potential. , 1985, Biochimica et biophysica acta.

[121]  P. Stauffer,et al.  Liposomes and hyperthermia in mice: increased tumor uptake and therapeutic efficacy of doxorubicin in sterically stabilized liposomes. , 1994, Cancer research.

[122]  J. Northrop,et al.  Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[123]  P. Cullis,et al.  Interactions of liposomes and lipid-based carrier systems with blood proteins: Relation to clearance behaviour in vivo. , 1998, Advanced drug delivery reviews.

[124]  P. Cullis,et al.  Separation of large unilamellar liposomes from blood components by a spin column procedure: towards identifying plasma proteins which mediate liposome clearance in vivo. , 1991, Biochimica et biophysica acta.

[125]  D. Tzemach,et al.  Liposome longevity and stability in circulation: effects on the in vivo delivery to tumors and therapeutic efficacy of encapsulated anthracyclines. , 1996, Journal of drug targeting.

[126]  G. Pond,et al.  Pegylated liposomal doxorubicin and trastuzumab in HER-2 overexpressing metastatic breast cancer: a multicenter phase II trial. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[127]  Norbert Maurer,et al.  Characterization of the drug retention and pharmacokinetic properties of liposomal nanoparticles containing dihydrosphingomyelin. , 2007, Biochimica et biophysica acta.

[128]  F. Chang,et al.  Simple and efficient liposomal encapsulation of topotecan by ammonium sulfate gradient: stability, pharmacokinetic and therapeutic evaluation , 2002, Anti-cancer drugs.

[129]  P. Steerenberg,et al.  Release of doxorubicin from peritoneal macrophages exposed in vivo to doxorubicin-containing liposomes. , 1988, Biochimica et biophysica acta.

[130]  C. Shapiro,et al.  Cardiac safety of liposomal anthracyclines. , 2004, Seminars in oncology.

[131]  Marc Dellian,et al.  Neovascular targeting therapy: paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[132]  I. Vorobyov,et al.  Conformational studies of sphingolipids by NMR spectroscopy. II. Sphingomyelin. , 2000, Biochimica et biophysica acta.

[133]  D. Papahadjopoulos,et al.  Role of cholesterol in membranes. Effects on phospholipid-protein interactions, membrane permeability and enzymatic activity. , 1973, Biochimica et biophysica acta.

[134]  J Verweij,et al.  Cremophor EL: the drawbacks and advantages of vehicle selection for drug formulation. , 2001, European journal of cancer.

[135]  P. Cullis,et al.  Influence of dose on liposome clearance: critical role of blood proteins. , 1996, Biochimica et biophysica acta.

[136]  M. Kool,et al.  A family of drug transporters: the multidrug resistance-associated proteins. , 2000, Journal of the National Cancer Institute.

[137]  G. Storm,et al.  Liposomes to target the lymphatics by subcutaneous administration. , 2001, Advanced drug delivery reviews.

[138]  F. Szoka,et al.  Efficiency of Cytoplasmic Delivery by pH-Sensitive Liposomes to Cells in Culture , 1990, Pharmaceutical Research.

[139]  F. Martin,et al.  Pharmacokinetics and antitumor activity of epirubicin encapsulated in long‐circulating liposomes incorporating a polyethylene glycol‐derivatized phospholipid , 1992, International journal of cancer.

[140]  T. Andresen,et al.  Advanced strategies in liposomal cancer therapy: problems and prospects of active and tumor specific drug release. , 2005, Progress in lipid research.

[141]  T. Ishida,et al.  Accelerated blood clearance of PEGylated liposomes upon repeated injections: effect of doxorubicin-encapsulation and high-dose first injection. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[142]  J. Zhang,et al.  The highly lipophilic DNA topoisomerase I inhibitor DB-67 displays elevated lactone levels in human blood and potent anticancer activity. , 2001, Journal of controlled release : official journal of the Controlled Release Society.

[143]  T. E. Thompson,et al.  Interaction of cholesterol with various glycerophospholipids and sphingomyelin. , 1990, Biochemistry.

[144]  Ulrik B Nielsen,et al.  Therapeutic efficacy of anti-ErbB2 immunoliposomes targeted by a phage antibody selected for cellular endocytosis. , 2002, Biochimica et biophysica acta.

[145]  M. Bally,et al.  Influence of drug release characteristics on the therapeutic activity of liposomal mitoxantrone. , 1997, The Journal of pharmacology and experimental therapeutics.

[146]  D. V. Hoff,et al.  A Phase 2 trial of the liposomal DACH platinum L-NDDP in patients with therapy-refractory advanced colorectal cancer , 2006, Cancer Chemotherapy and Pharmacology.

[147]  M. Zeidel,et al.  The relationship between membrane fluidity and permeabilities to water, solutes, ammonia, and protons , 1995, The Journal of general physiology.

[148]  L. Mayer,et al.  Determination of free and liposome-associated doxorubicin and vincristine levels in plasma under equilibrium conditions employing ultrafiltration techniques. , 1995, Analytical biochemistry.

[149]  S. Mantripragada A lipid based depot (DepoFoam technology) for sustained release drug delivery. , 2002, Progress in lipid research.

[150]  S. Kawakami,et al.  Physicochemical and pharmacokinetic characteristics of cationic liposomes. , 2006, Die Pharmazie.

[151]  J H Senior,et al.  Fate and behavior of liposomes in vivo: a review of controlling factors. , 1987, Critical reviews in therapeutic drug carrier systems.

[152]  Y. Barenholz,et al.  Gelation of liposome interior A novel method for drug encapsulation , 1992, FEBS letters.

[153]  Theresa M. Allen,et al.  Pharmacokinetics of long-circulating liposomes , 1995 .

[154]  F. Fraternali,et al.  Hydrogen-bonding propensities of sphingomyelin in solution and in a bilayer assembly: a molecular dynamics study. , 2003, Biophysical journal.

[155]  M. Berger,et al.  Distribution of Liposomes into Brain and Rat Brain Tumor Models by Convection-Enhanced Delivery Monitored with Magnetic Resonance Imaging , 2004, Cancer Research.

[156]  Y. Barenholz,et al.  Transmembrane ammonium sulfate gradients in liposomes produce efficient and stable entrapment of amphipathic weak bases. , 1993, Biochimica et biophysica acta.

[157]  R. Rietbroek,et al.  Hyperthermia enhances tumor uptake and antitumor efficacy of thermostable liposomal daunorubicin in a rat solid tumor. , 1996, Cancer research.

[158]  T. Zhang,et al.  Liposome-anchored vascular endothelial growth factor aptamers. , 1998, Bioconjugate chemistry.

[159]  K. Matthay,et al.  Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes. , 1992, Biochimica et biophysica acta.

[160]  N. Van Rooijen,et al.  Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes. , 1994, Biochimica et biophysica acta.

[161]  D. Papahadjopoulos,et al.  Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. , 1999, Pharmacological reviews.

[162]  M. Newman,et al.  Pharmacokinetics, Biodistribution and Therapeutic Efficacy of Doxorubicin Encapsulated in Stealth® Liposomes (Doxil®) , 1994 .

[163]  D. Mager,et al.  Effect of Repetitive Administration of Doxorubicin-Containing Liposomes on Plasma Pharmacokinetics and Drug Biodistribution in a Rat Brain Tumor Model , 2005, Clinical Cancer Research.

[164]  Theresa M Allen,et al.  Rate of biodistribution of STEALTH liposomes to tumor and skin: influence of liposome diameter and implications for toxicity and therapeutic activity. , 2003, Biochimica et biophysica acta.

[165]  M. Dewhirst,et al.  In vivo monitoring of tissue pharmacokinetics of liposome/drug using MRI: Illustration of targeted delivery , 2004, Magnetic resonance in medicine.

[166]  E. Chang,et al.  Systemic tumor-targeted gene delivery by anti-transferrin receptor scFv-immunoliposomes. , 2002, Molecular cancer therapeutics.

[167]  P. Kramer,et al.  Liposomal entrapment of floxuridine. , 1977, Journal of pharmaceutical sciences.

[168]  J. Lehn,et al.  The design of cationic lipids for gene delivery. , 2005, Current pharmaceutical design.

[169]  P. Cullis,et al.  Factors influencing the retention and chemical stability of poly(ethylene glycol)-lipid conjugates incorporated into large unilamellar vesicles. , 1994, Biochimica et biophysica acta.

[170]  F. Szoka,et al.  Lipid-based Nanoparticles for Nucleic Acid Delivery , 2007, Pharmaceutical Research.

[171]  R. Jain,et al.  Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[172]  Mark W Dewhirst,et al.  Magnetic resonance imaging of temperature-sensitive liposome release: drug dose painting and antitumor effects. , 2007, Journal of the National Cancer Institute.

[173]  J. Correia,et al.  Vinca alkaloid-induced tubulin spiral formation correlates with cytotoxicity in the leukemic L1210 cell line. , 2000, Biochemistry.

[174]  C. Cass,et al.  The role of nucleoside transporters in cancer chemotherapy with nucleoside drugs , 2007, Cancer and Metastasis Reviews.

[175]  R. Rifkin,et al.  Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma , 2006, Cancer.

[176]  M. Bally,et al.  Liposomal encapsulation of topotecan enhances anticancer efficacy in murine and human xenograft models. , 2000, Cancer research.

[177]  J. Schellens,et al.  Systemic and tumor disposition of platinum after administration of cisplatin or STEALTH liposomal-cisplatin formulations (SPI-077 and SPI-077 B103) in a preclinical tumor model of melanoma , 2004, Cancer Chemotherapy and Pharmacology.

[178]  J. M. Smaby,et al.  Cholesterol decreases the interfacial elasticity and detergent solubility of sphingomyelins. , 2001, Biochemistry.

[179]  P. Ahl,et al.  Elastase activated liposomal delivery to nucleated cells. , 1999, Biochimica et biophysica acta.

[180]  M. Bally,et al.  A two-step targeting approach for delivery of doxorubicin-loaded liposomes to tumour cells in vivo , 2004, Cancer Chemotherapy and Pharmacology.

[181]  M. Dellian,et al.  Neovascular targeting chemotherapy: Encapsulation of paclitaxel in cationic liposomes impairs functional tumor microvasculature , 2004, International journal of cancer.

[182]  G. Gregoriadis,et al.  The effect of lipid composition of small unilamellar liposomes containing melphalan and vincristine on drug clearance after injection into mice. , 1983, Biochemical pharmacology.

[183]  L. Mayer,et al.  Liposomal and nonliposomal drug pharmacokinetics after administration of liposome-encapsulated vincristine and their contribution to drug tissue distribution properties. , 2001, The Journal of pharmacology and experimental therapeutics.

[184]  C. Benz,et al.  Genospheres: self-assembling nucleic acid-lipid nanoparticles suitable for targeted gene delivery , 2006, Gene Therapy.

[185]  Francis C Szoka,et al.  Barriers to carrier mediated drug and gene delivery to brain tumors. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[186]  L. Huang,et al.  Some negatively charged phospholipid derivatives prolong the liposome circulation in vivo. , 1992, Biochimica et biophysica acta.

[187]  P. Cullis,et al.  Influence of cholesterol on the association of plasma proteins with liposomes. , 1996, Biochemistry.

[188]  R. Zhou,et al.  Antivasculature effects of doxorubicin-containing liposomes in an intracranial rat brain tumor model. , 2002, Cancer research.

[189]  G. Scherphof,et al.  Transfer and exchange of phospholipid between small unilamellar liposomes and rat plasma high density lipoproteins. Dependence on cholesterol content and phospholipid composition. , 1981, Biochimica et biophysica acta.

[190]  M. Dewhirst,et al.  The development and testing of a new temperature-sensitive drug delivery system for the treatment of solid tumors. , 2001, Advanced drug delivery reviews.

[191]  J Szebeni,et al.  Stealth liposomes and long circulating nanoparticles: critical issues in pharmacokinetics, opsonization and protein-binding properties. , 2003, Progress in lipid research.

[192]  S. Clerc,et al.  Loading of amphipathic weak acids into liposomes in response to transmembrane calcium acetate gradients. , 1995, Biochimica et biophysica acta.

[193]  M. Bally,et al.  In Vitro and in Vivo Characterization of Doxorubicin and Vincristine Coencapsulated within Liposomes through Use of Transition Metal Ion Complexation and pH Gradient Loading , 2004, Clinical Cancer Research.

[194]  R. Bankert,et al.  Antibody targeting of doxorubicin-loaded liposomes suppresses the growth and metastatic spread of established human lung tumor xenografts in severe combined immunodeficient mice. , 2000, Cancer research.

[195]  Vladimir P Torchilin,et al.  Recent approaches to intracellular delivery of drugs and DNA and organelle targeting. , 2006, Annual review of biomedical engineering.

[196]  J. Zhang,et al.  Development and characterization of a novel Cremophor EL free liposome-based paclitaxel (LEP-ETU) formulation. , 2005, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[197]  A. Spector,et al.  Membrane cholesterol and phospholipid in consecutive concentric sections of human lenses. , 1985, Journal of lipid research.

[198]  D. Tzemach,et al.  Correlation of toxicity with pharmacokinetics of pegylated liposomal doxorubicin (Doxil) in metastatic breast carcinoma , 2000, Cancer.

[199]  A. Gabizon,et al.  Liposome circulation time and tumor targeting: implications for cancer chemotherapy , 1995 .

[200]  P. van Hoogevest,et al.  Lipophilic Drug Transfer Between Liposomal and Biological Membranes: What Does It Mean for Parenteral and Oral Drug Delivery? , 2006, Journal of liposome research.

[201]  M. Woodle,et al.  Pharmacokinetics and anti‐tumor activity of vincristine encapsulated in sterically stabilized liposomes , 1995, International journal of cancer.

[202]  Yechezkel Barenholz,et al.  Pharmacokinetics of Pegylated Liposomal Doxorubicin , 2003, Clinical pharmacokinetics.

[203]  D. Papahadjopoulos,et al.  The introduction of poliovirus RNA into cells via lipid vesicles (liposomes) , 1979, Cell.

[204]  P. Cullis,et al.  Factors influencing uptake and retention of amino-containing drugs in large unilamellar vesicles exhibiting transmembrane pH gradients. , 1999, Biochimica et biophysica acta.

[205]  F. Szoka,et al.  Role of cholesterol in enhancing the antitumor activity of cytosine arabinoside entrapped in liposomes. , 1979, Cancer treatment reports.

[206]  M. Newman,et al.  Relationship of dose intensity to the induction of palmar-plantar erythrodysesthia by pegylated liposomal doxorubicin in dogs , 1999, Human & experimental toxicology.

[207]  Theresa M Allen,et al.  Advantages of liposomal delivery systems for anthracyclines. , 2004, Seminars in oncology.

[208]  O. Kaalhus,et al.  Radiation Improves the Distribution and Uptake of Liposomal Doxorubicin (Caelyx) in Human Osteosarcoma Xenografts , 2004, Cancer Research.

[209]  K. Edwards,et al.  Formation of drug-arylsulfonate complexes inside liposomes: a novel approach to improve drug retention. , 2006, Journal of controlled release : official journal of the Controlled Release Society.

[210]  T. Allen A study of phospholipid interactions between high-density lipoproteins and small unilamellar vesicles. , 1981, Biochimica et biophysica acta.

[211]  Feng Liu,et al.  Implications of pharmacokinetic behavior of lipoplex for its inflammatory toxicity. , 2005, Advanced drug delivery reviews.

[212]  Perttu S. Niemelä,et al.  Structure and dynamics of sphingomyelin bilayer: insight gained through systematic comparison to phosphatidylcholine. , 2004, Biophysical journal.

[213]  D. Drummond,et al.  Synthesis and characterization of N-acylated, pH-sensitive 'caged' aminophospholipids. , 1995, Chemistry and physics of lipids.

[214]  K. Kono,et al.  Novel gene delivery systems: complexes of fusigenic polymer-modified liposomes and lipoplexes , 2001, Gene Therapy.

[215]  Matthias John,et al.  RNAi-mediated gene silencing in non-human primates , 2006, Nature.

[216]  T. Allen,et al.  Subcutaneous administration of liposomes: a comparison with the intravenous and intraperitoneal routes of injection. , 1993, Biochimica et biophysica acta.

[217]  M. Angst,et al.  Pharmacology of Drugs Formulated with DepoFoam™ , 2006, Clinical pharmacokinetics.

[218]  Bengt Rippe,et al.  Glomerular filtration rate dependence of sieving of albumin and some neutral proteins in rat kidneys. , 2003, American journal of physiology. Renal physiology.

[219]  M. Yessine,et al.  Membrane-destabilizing polyanions: interaction with lipid bilayers and endosomal escape of biomacromolecules. , 2004, Advanced drug delivery reviews.

[220]  J. Heyes,et al.  Stabilized plasmid-lipid particles containing PEG-diacylglycerols exhibit extended circulation lifetimes and tumor selective gene expression. , 2005, Biochimica et biophysica acta.

[221]  P. Cullis,et al.  Association of blood proteins with large unilamellar liposomes in vivo. Relation to circulation lifetimes. , 1992, The Journal of biological chemistry.

[222]  R. Bittman,et al.  Interaction of cholesterol with sphingomyelin in monolayers and vesicles. , 1994, Biochemistry.

[223]  C. Mamot,et al.  Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. , 2005, Cancer research.

[224]  M. Berger,et al.  Novel nanoliposomal CPT-11 infused by convection-enhanced delivery in intracranial tumors: pharmacology and efficacy. , 2006, Cancer research.

[225]  Theresa M Allen,et al.  Multiple Injections of Pegylated Liposomal Doxorubicin: Pharmacokinetics and Therapeutic Activity , 2003, Journal of Pharmacology and Experimental Therapeutics.

[226]  W. Oyen,et al.  Preclinical and clinical evidence for disappearance of long-circulating characteristics of polyethylene glycol liposomes at low lipid dose. , 2000, The Journal of pharmacology and experimental therapeutics.

[227]  David H. Thompson,et al.  Phototriggering of liposomal drug delivery systems. , 2001, Advanced drug delivery reviews.

[228]  Christopher Poole,et al.  Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[229]  M. Berger,et al.  Tissue affinity of the infusate affects the distribution volume during convection-enhanced delivery into rodent brains: Implications for local drug delivery , 2006, Journal of Neuroscience Methods.

[230]  M. Hope,et al.  Antibacterial Efficacy against an In Vivo Salmonella typhimurium Infection Model and Pharmacokinetics of a Liposomal Ciprofloxacin Formulation , 1998, Antimicrobial Agents and Chemotherapy.

[231]  Imran Ahmad,et al.  Development and characterization of a novel liposome-based formulation of SN-38. , 2004, International journal of pharmaceutics.

[232]  F. Khuri,et al.  A phase II study of STEALTH cisplatin (SPI-77) in patients with advanced non-small cell lung cancer. , 2001, Lung cancer.

[233]  M. Berger,et al.  Convection-enhanced delivery of Ls-TPT enables an effective, continuous, low-dose chemotherapy against malignant glioma xenograft model. , 2006, Neuro-oncology.

[234]  D. Thompson,et al.  Acid-triggered release via dePEGylation of DOPE liposomes containing acid-labile vinyl ether PEG-lipids. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[235]  M A Fischl,et al.  Pegylated-liposomal doxorubicin versus doxorubicin, bleomycin, and vincristine in the treatment of AIDS-related Kaposi's sarcoma: results of a randomized phase III clinical trial. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[236]  B. Haraldsson,et al.  Glomerular size and charge selectivity in the rat as revealed by FITC-ficoll and albumin. , 2000, American journal of physiology. Renal physiology.

[237]  S. Bhatia,et al.  Enhancement of the in vivo circulation lifetime of L-alpha-distearoylphosphatidylcholine liposomes: importance of liposomal aggregation versus complement opsonization. , 1997, Biochimica et biophysica acta.

[238]  H. D. Liggitt,et al.  Factors influencing the efficiency of cationic liposome-mediated intravenous gene delivery , 1997, Nature Biotechnology.

[239]  A. Gabizon,et al.  Pharmacokinetics and tissue distribution of doxorubicin encapsulated in stable liposomes with long circulation times. , 1989, Journal of the National Cancer Institute.

[240]  P Berg,et al.  Introduction of liposome-encapsulated SV40 DNA into cells. , 1980, The Journal of biological chemistry.

[241]  M. Hope,et al.  Immunogenicity and Rapid Blood Clearance of Liposomes Containing Polyethylene Glycol-Lipid Conjugates and Nucleic Acid , 2005, Journal of Pharmacology and Experimental Therapeutics.

[242]  P. Cullis,et al.  Effects of intravenous and subcutaneous administration on the pharmacokinetics, biodistribution, cellular uptake and immunostimulatory activity of CpG ODN encapsulated in liposomal nanoparticles. , 2007, International immunopharmacology.

[243]  S. Haupt,et al.  Drug targeting by surface cationization. , 2000, Critical reviews in therapeutic drug carrier systems.

[244]  Francis C Szoka,et al.  Low-pH-sensitive PEG-stabilized plasmid-lipid nanoparticles: preparation and characterization. , 2003, Bioconjugate chemistry.

[245]  C. Verschraegen,et al.  Clinical Evaluation of the Delivery and Safety of Aerosolized Liposomal 9-Nitro-20(S)-Camptothecin in Patients with Advanced Pulmonary Malignancies , 2004, Clinical Cancer Research.

[246]  Joseph Kost,et al.  Controlling liposomal drug release with low frequency ultrasound: mechanism and feasibility. , 2007, Langmuir : the ACS journal of surfaces and colloids.

[247]  M. Bally,et al.  Controlled destabilization of a liposomal drug delivery system enhances mitoxantrone antitumor activity , 1999, Nature Biotechnology.

[248]  D. McDonald,et al.  Organ-specific endothelial cell uptake of cationic liposome-DNA complexes in mice. , 1997, The American journal of physiology.

[249]  K. Edwards,et al.  Optimization and characterization of a sphingomyelin/cholesterol liposome formulation of vinorelbine with promising antitumor activity. , 2005, Journal of pharmaceutical sciences.

[250]  E. C. Beuvery,et al.  Comparison of four bifunctional reagents for coupling peptides to proteins and the effect of the three moieties on the immunogenicity of the conjugates. , 1989, Journal of immunological methods.

[251]  M. Bally,et al.  Comparison of different hydrophobic anchors conjugated to poly(ethylene glycol): effects on the pharmacokinetics of liposomal vincristine. , 1998, Biochimica et biophysica acta.

[252]  M. Bally,et al.  CHAPTER 4.2 – Designing therapeutically optimized liposomal anticancer delivery systems: Lessons from conventional liposomes , 1998 .

[253]  J. Dijkstra,et al.  Interaction of liposomes with Kupffer cells in vitro. , 1984, Experimental cell research.

[254]  T M Allen,et al.  In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. , 1998, Cancer research.

[255]  M. Bally,et al.  Sphingomyelin-cholesterol liposomes significantly enhance the pharmacokinetic and therapeutic properties of vincristine in murine and human tumour models. , 1995, British Journal of Cancer.

[256]  H. Maeda,et al.  A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. , 1986, Cancer research.

[257]  G. Kenner,et al.  Influence of poly(ethylene glycol) grafting density and polymer length on liposomes: relating plasma circulation lifetimes to protein binding. , 2007, Biochimica et biophysica acta.

[258]  D. Papahadjopoulos,et al.  Ultrastructural characterization of cationic liposome-DNA complexes showing enhanced stability in serum and high transfection activity in vivo. , 1998, Biochimica et biophysica acta.

[259]  P. Cullis,et al.  Liposome-encapsulated vincristine, vinblastine and vinorelbine: a comparative study of drug loading and retention. , 2005, Journal of controlled release : official journal of the Controlled Release Society.

[260]  G. Wood,et al.  Targeting of the Antivascular Drug Combretastatin to Irradiated Tumors Results in Tumor Growth Delay , 2005, Pharmaceutical Research.

[261]  Michael Hawkins,et al.  Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[262]  T. Allen,et al.  Ligand-targeted liposomal anticancer drugs. , 2003, Progress in lipid research.

[263]  C. Brayton,et al.  9-NITROCAMPTOTHECIN LIPOSOME AEROSOL: LACK OF SUBACUTE TOXICITY IN DOGS , 2002, Inhalation toxicology.

[264]  D Needham,et al.  Elastic deformation and failure of lipid bilayer membranes containing cholesterol. , 1990, Biophysical journal.

[265]  Y. Barenholz,et al.  Targeted Delivery of Doxorubicin via Sterically Stabilized Immunoliposomes: Pharmacokinetics and Biodistribution in Tumor-bearing Mice , 1996, Pharmaceutical Research.

[266]  H. Groen,et al.  Phase I and pharmacologic study of liposomal lurtotecan, NX 211: urinary excretion predicts hematologic toxicity. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[267]  H. Harashima,et al.  Pharmacokinetic/pharmacodynamic modeling of antitumor agents encapsulated into liposomes. , 1999, Advanced drug delivery reviews.

[268]  J. Drevs,et al.  Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study , 2004, Cancer Chemotherapy and Pharmacology.

[269]  F. Dosio,et al.  Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing water-soluble prodrugs of paclitaxel. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[270]  N Thatcher,et al.  Phase II study of SPI-77 (sterically stabilised liposomal cisplatin) in advanced non-small-cell lung cancer , 2006, British Journal of Cancer.

[271]  T. Allen,et al.  Pharmacokinetics of stealth versus conventional liposomes: effect of dose. , 1991, Biochimica et biophysica acta.

[272]  B. Tromberg,et al.  Fluorescence imaging studies for the disposition of daunorubicin liposomes (DaunoXome) within tumor tissue. , 1996, Cancer research.

[273]  Theresa M. Allen,et al.  Determination of Doxorubicin Levels in Whole Tumor and Tumor Nuclei in Murine Breast Cancer Tumors , 2005, Clinical Cancer Research.

[274]  M. Bally,et al.  Coencapsulation of irinotecan and floxuridine into low cholesterol-containing liposomes that coordinate drug release in vivo. , 2007, Biochimica et biophysica acta.

[275]  E. Moase,et al.  Improved Therapeutic Responses in a Xenograft Model of Human B Lymphoma (Namalwa) for Liposomal Vincristine versus Liposomal Doxorubicin Targeted via Anti-CD19 IgG2a or Fab′ Fragments , 2004, Clinical Cancer Research.

[276]  U. Nielsen,et al.  Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. , 2006, Cancer research.

[277]  Keith Bowman,et al.  Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs , 2005, Nature Biotechnology.

[278]  Vladimir P Torchilin,et al.  Cationic charge determines the distribution of liposomes between the vascular and extravascular compartments of tumors. , 2002, Cancer research.

[279]  Theresa M Allen,et al.  Anti-CD19-Targeted Liposomal Doxorubicin Improves the Therapeutic Efficacy in Murine B-Cell Lymphoma and Ameliorates the Toxicity of Liposomes with Varying Drug Release Rates , 2005, Clinical Cancer Research.

[280]  T. Ishida,et al.  Accelerated clearance of PEGylated liposomes in rats after repeated injections. , 2003, Journal of controlled release : official journal of the Controlled Release Society.

[281]  A. Urtti,et al.  Extracellular Glycosaminoglycans Modify Cellular Trafficking of Lipoplexes and Polyplexes* , 2001, The Journal of Biological Chemistry.

[282]  M. Stuart,et al.  Transmembrane gradient driven phase transitions within vesicles: lessons for drug delivery. , 1995, Biochimica et biophysica acta.

[283]  P. Uster,et al.  Encapsulation of the topoisomerase I inhibitor GL147211C in pegylated (STEALTH) liposomes: pharmacokinetics and antitumor activity in HT29 colon tumor xenografts. , 1998, Clinical cancer research : an official journal of the American Association for Cancer Research.

[284]  G. Gregoriadis,et al.  Stability of small unilamellar liposomes in serum and clearance from the circulation: the effect of the phospholipid and cholesterol components. , 1982, Life sciences.

[285]  Philip S Low,et al.  Evaluation of disulfide reduction during receptor-mediated endocytosis by using FRET imaging , 2006, Proceedings of the National Academy of Sciences.

[286]  M. Bally,et al.  Liposomes with entrapped doxorubicin exhibit extended blood residence times. , 1990, Biochimica et biophysica acta.

[287]  John W. Park,et al.  Development of a highly active nanoliposomal irinotecan using a novel intraliposomal stabilization strategy. , 2006, Cancer research.

[288]  J. Leroux,et al.  In vitro characterization of a novel polymeric-based pH-sensitive liposome system. , 2000, Biochimica et biophysica acta.

[289]  J. Hagstrom,et al.  pH-sensitive, cationic liposomes: A new synthetic virus-like vector , 1996, Nature Biotechnology.

[290]  W. Guo,et al.  Paclitaxel quantification in mouse plasma and tissues containing liposome-entrapped paclitaxel by liquid chromatography-tandem mass spectrometry: application to a pharmacokinetics study. , 2005, Analytical biochemistry.

[291]  M. Bally,et al.  Accumulation of liposomal lipid and encapsulated doxorubicin in murine Lewis lung carcinoma: the lack of beneficial effects by coating liposomes with poly(ethylene glycol). , 1997, The Journal of pharmacology and experimental therapeutics.

[292]  S. Parker,et al.  Tissue distribution of the cytofectin component of a plasmid-DNA/cationic lipid complex following intravenous administration in mice. , 1997, Human gene therapy.

[293]  F. Szoka,et al.  Cyclic amphipathic peptide-DNA complexes mediate high-efficiency transfection of adherent mammalian cells. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[294]  Ryuta Saito,et al.  Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain , 2005, Experimental Neurology.

[295]  K. Mechtler,et al.  Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery. , 1996, Human gene therapy.

[296]  C G Morgan,et al.  Active Uptake of Drugs into Photosensitive Liposomes and Rapid Release on UV Photolysis¶ , 2000, Photochemistry and photobiology.

[297]  D. Scherman,et al.  Reducible cationic lipids for gene transfer. , 2001, The Biochemical journal.

[298]  Paul R. Lockman,et al.  Nanoparticle Surface Charges Alter Blood–Brain Barrier Integrity and Permeability , 2004, Journal of drug targeting.

[299]  Dayan Ad Pharmacological-toxicological expert report. CAELYX. (Stealth liposomal doxorubicin HCl). , 1996 .

[300]  D. Ribatti,et al.  Targeted liposomal c-myc antisense oligodeoxynucleotides induce apoptosis and inhibit tumor growth and metastases in human melanoma models. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[301]  F. Szoka,et al.  pH-dependent fusion of phosphatidylcholine small vesicles. Induction by a synthetic amphipathic peptide. , 1988, The Journal of biological chemistry.

[302]  P. Cullis,et al.  Ionophore-mediated uptake of ciprofloxacin and vincristine into large unilamellar vesicles exhibiting transmembrane ion gradients. , 1998, Biochimica et biophysica acta.

[303]  F. Goñi,et al.  Interaction of cholesterol with sphingomyelin in mixed membranes containing phosphatidylcholine, studied by spin-label ESR and IR spectroscopies. A possible stabilization of gel-phase sphingolipid domains by cholesterol. , 2001, Biochemistry.