The Experts below are selected from a list of 1632 Experts worldwide ranked by ideXlab platform

Thomas D Madden - One of the best experts on this subject based on the ideXlab platform.

  • controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity
    Nature Biotechnology, 1999
    Co-Authors: Gitanjali Adlakhahutcheon, Marcel B Bally, Clifford Shew, Thomas D Madden
    Abstract:

    Controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity

  • Controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity
    Nature Biotechnology, 1999
    Co-Authors: Gitanjali Adlakha-hutcheon, Marcel B Bally, Clifford Shew, Thomas D Madden
    Abstract:

    Programmable fusogenic vesicles (PFVs) are lipid-based Drug-Delivery systems that exhibit time-dependent destabilization. The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from the vesicle surface. This exchange rate is controlled, in turn, by the acyl chain composition of the PEG-PE. We describe in vitro and in vivo studies using PFVs as Delivery vehicles for the anticancer Drug mitoxantrone. We demonstrate that the PEG-PE acyl composition determined the rate at which PFVs are eliminated from plasma after intravenous administration, and the rate of mitoxantrone leakage from PFV. The nature of the PEG-PE component also determined the antitumor efficacy of mitoxantrone-loaded PFV in murine and human in murine and human xenograft tumor models. Increased circulation time and improved activity were obtained for PFV containing PEG-PE with an 18-carbon acyl chain length, as a result of slower vesicle destabilization.

Theresa M. Allen - One of the best experts on this subject based on the ideXlab platform.

  • Liposomal Drug Delivery systems: From concept to clinical applications
    Advanced Drug Delivery Reviews, 2013
    Co-Authors: Theresa M. Allen, PIETER RUTTER CULLIS
    Abstract:

    The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as Drug Delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote Drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of Drugs. These advances have led to numerous clinical trials in such diverse areas as the Delivery of anti-cancer, anti-fungal and antibiotic Drugs, the Delivery of gene medicines, and the Delivery of anesthetics and anti-inflammatory Drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine Delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future. © 2012 Elsevier B.V.

  • Liposomal Drug Delivery systems from concept to clinical applications
    Advanced Drug Delivery Reviews, 2013
    Co-Authors: Theresa M. Allen, PIETER RUTTER CULLIS
    Abstract:

    The first closed bilayer phospholipid systems, called liposomes, were described in 1965 and soon were proposed as Drug Delivery systems. The pioneering work of countless liposome researchers over almost 5 decades led to the development of important technical advances such as remote Drug loading, extrusion for homogeneous size, long-circulating (PEGylated) liposomes, triggered release liposomes, liposomes containing nucleic acid polymers, ligand-targeted liposomes and liposomes containing combinations of Drugs. These advances have led to numerous clinical trials in such diverse areas as the Delivery of anti-cancer, anti-fungal and antibiotic Drugs, the Delivery of gene medicines, and the Delivery of anesthetics and anti-inflammatory Drugs. A number of liposomes (lipidic nanoparticles) are on the market, and many more are in the pipeline. Lipidic nanoparticles are the first nanomedicine Delivery system to make the transition from concept to clinical application, and they are now an established technology platform with considerable clinical acceptance. We can look forward to many more clinical products in the future.

  • Medical Applications of Liposomes - CHAPTER 4.6 – Targeted sterically stabilized Liposomal Drug Delivery
    Medical Applications of Liposomes, 1998
    Co-Authors: Theresa M. Allen, Christian B Hansen, Darrin D Stuart
    Abstract:

    This chapter provides an overview of targeted Liposomal Drug Delivery and potential problems with targeted liposomes. Drug carriers, such as liposomes, are used in attempts to improve the therapeutic index of associated therapeutic molecules. Selective Drug Delivery to cancer cells requires the presence of markers on the cancer cell surface, which distinguishes them from non-tumor cells. These markers are often referred to as tumor-associated antigens. In some cases, the antigen is well characterized and is known to be a receptor, which is mutated or over expressed on the tumor cells, while in other cases the antigen is simply characterized as a cell surface glycoprotein with uncharacterized structure or function. Ligands that are used specifically to target cancer cells are monoclonal antibodies. Several problems identified with targeted liposomes are: rapid clearance of immunoliposomes, target tissue heterogeneity, and binding site barrier. In recent years, significant progress has been achieved in attempts to gain specific targeting of Drugs in vivo . These include: development of long-circulating immunoliposomes, adaptation of existing chemistries, and the development of new strategies for coupling ligands to the surface of liposomes.

  • chapter 4 6 targeted sterically stabilized Liposomal Drug Delivery
    Medical Applications of Liposomes, 1998
    Co-Authors: Theresa M. Allen, Christian B Hansen, Darrin D Stuart
    Abstract:

    This chapter provides an overview of targeted Liposomal Drug Delivery and potential problems with targeted liposomes. Drug carriers, such as liposomes, are used in attempts to improve the therapeutic index of associated therapeutic molecules. Selective Drug Delivery to cancer cells requires the presence of markers on the cancer cell surface, which distinguishes them from non-tumor cells. These markers are often referred to as tumor-associated antigens. In some cases, the antigen is well characterized and is known to be a receptor, which is mutated or over expressed on the tumor cells, while in other cases the antigen is simply characterized as a cell surface glycoprotein with uncharacterized structure or function. Ligands that are used specifically to target cancer cells are monoclonal antibodies. Several problems identified with targeted liposomes are: rapid clearance of immunoliposomes, target tissue heterogeneity, and binding site barrier. In recent years, significant progress has been achieved in attempts to gain specific targeting of Drugs in vivo . These include: development of long-circulating immunoliposomes, adaptation of existing chemistries, and the development of new strategies for coupling ligands to the surface of liposomes.

  • Liposomes
    Drugs, 1997
    Co-Authors: Theresa M. Allen
    Abstract:

    Liposomal Drug Delivery systems markedly alter the biodistribution of their associated Drugs by delaying Drug clearance, retarding Drug metabolism, decreasing the volume of distribution, and shifting the distribution in favour of diseased tissues with increased capillary permeability. This increases the therapeutic indices of the associated Drugs, by increasing the Drug concentration in solid tumours and regions of infection, and reducing the Drug concentration in normal tissues. Three Liposomal formulations have been approved for clinical use.

Marcel B Bally - One of the best experts on this subject based on the ideXlab platform.

  • Liposomal Drug Delivery: Recent Patents and Emerging Opportunities
    Recent Patents on Drug Delivery & Formulation, 2007
    Co-Authors: Murray S. Webb, Patrick Rebstein, Wendy Lamson, Marcel B Bally
    Abstract:

    It is challenging to develop innovative, as well as commercially viable, lipid-based Drug Delivery systems for the treatment of cancer because of the breadth of existing intellectual property that limits freedom-to-operate. For example, novel compositions can be described in which a new chemical entity is associated with a lipid based carrier, but if the loading method or components of the lipid compositions are proprietary then the ability to develop novel compositions will require access to the appropriate intellectual property. We believe it is useful to present a review of the patent literature describing novel Liposomal Drug Delivery systems given by parenteral administration to humans for the treatment of serious medical conditions such as cancer. This review is intended to: (i) identify and describe novel approaches that have recently been protected by US or international patents and patent applications, and; (ii) identify founding technology in the field which is recently off-patent, thus presenting emerging opportunities for the development of new therapeutic options for patients. Issued patents, and selected patent applications, having publication dates in 2005 or 2006 were retrieved from searches of the US, European, German, Japanese, INPADOC and WIPO PCT databases. Liposomal Delivery systems patented for systemic administration in the treatment of human medical conditions were reviewed in detail.

  • controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity
    Nature Biotechnology, 1999
    Co-Authors: Gitanjali Adlakhahutcheon, Marcel B Bally, Clifford Shew, Thomas D Madden
    Abstract:

    Controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity

  • Controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity
    Nature Biotechnology, 1999
    Co-Authors: Gitanjali Adlakha-hutcheon, Marcel B Bally, Clifford Shew, Thomas D Madden
    Abstract:

    Programmable fusogenic vesicles (PFVs) are lipid-based Drug-Delivery systems that exhibit time-dependent destabilization. The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from the vesicle surface. This exchange rate is controlled, in turn, by the acyl chain composition of the PEG-PE. We describe in vitro and in vivo studies using PFVs as Delivery vehicles for the anticancer Drug mitoxantrone. We demonstrate that the PEG-PE acyl composition determined the rate at which PFVs are eliminated from plasma after intravenous administration, and the rate of mitoxantrone leakage from PFV. The nature of the PEG-PE component also determined the antitumor efficacy of mitoxantrone-loaded PFV in murine and human in murine and human xenograft tumor models. Increased circulation time and improved activity were obtained for PFV containing PEG-PE with an 18-carbon acyl chain length, as a result of slower vesicle destabilization.

Clifford Shew - One of the best experts on this subject based on the ideXlab platform.

  • controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity
    Nature Biotechnology, 1999
    Co-Authors: Gitanjali Adlakhahutcheon, Marcel B Bally, Clifford Shew, Thomas D Madden
    Abstract:

    Controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity

  • Controlled destabilization of a Liposomal Drug Delivery system enhances mitoxantrone antitumor activity
    Nature Biotechnology, 1999
    Co-Authors: Gitanjali Adlakha-hutcheon, Marcel B Bally, Clifford Shew, Thomas D Madden
    Abstract:

    Programmable fusogenic vesicles (PFVs) are lipid-based Drug-Delivery systems that exhibit time-dependent destabilization. The rate at which this destabilization occurs is determined by the exchange rate of a bilayer-stabilizing component, polyethylene glycol-phosphatidylethanolamine (PEG-PE) from the vesicle surface. This exchange rate is controlled, in turn, by the acyl chain composition of the PEG-PE. We describe in vitro and in vivo studies using PFVs as Delivery vehicles for the anticancer Drug mitoxantrone. We demonstrate that the PEG-PE acyl composition determined the rate at which PFVs are eliminated from plasma after intravenous administration, and the rate of mitoxantrone leakage from PFV. The nature of the PEG-PE component also determined the antitumor efficacy of mitoxantrone-loaded PFV in murine and human in murine and human xenograft tumor models. Increased circulation time and improved activity were obtained for PFV containing PEG-PE with an 18-carbon acyl chain length, as a result of slower vesicle destabilization.

Takayuki Ishii - One of the best experts on this subject based on the ideXlab platform.

  • Applications of Liposomal Drug Delivery Systems to Develop Neuroprotective Agents for the Treatment of Ischemic Stroke.
    Biological & Pharmaceutical Bulletin, 2019
    Co-Authors: Tatsuya Fukuta, Takayuki Ishii, Tomohiro Asai
    Abstract:

    : Ischemic stroke is one of the leading causes of severe disability and death. In clinical settings, tissue plasminogen activator (t-PA) for thrombolytic therapy is the only globally approved Drug for the treatment of ischemic stroke. However, the proportion of patients who receive t-PA therapy is extremely limited due to its narrow therapeutic time window (TTW) and the risk of cerebral hemorrhage. Cerebral ischemia-reperfusion (I/R) injury is also a serious problem for patients' outcomes. Hence, the development of more effective therapies has been desired to prolong the TTW of t-PA and prevent cerebral I/R injury. For delivering Drugs into the brain, the blood-brain barrier (BBB) must be overcome since it limits Drug penetration into the brain, leading to insufficient therapeutic efficacy. As a distinctive pathology after an ischemic stroke, it was reported that the vascular permeability of the BBB is increased around the ischemic region. We found that nano-sized liposomes can pass through the disrupted BBB and accumulate in the I/R region, and that Delivery of neuroprotective agents using a Liposomal Drug Delivery system (DDS) is effective for the treatment of cerebral I/R injury. Moreover, we have recently demonstrated that combination therapy with Liposomal Drugs and t-PA can suppress the deleterious effects of t-PA and extend its TTW in a rat ischemic stroke model. These findings indicate that applications of nanoparticle DDS technology could be a hopeful approach to Drug development for ischemic stroke therapy. In this review, we introduce our findings on ischemic stroke treatment using Liposomal DDS and recent advances from other research groups.

  • amelioration of cerebral ischemia reperfusion injury based on Liposomal Drug Delivery system with asialo erythropoietin
    Journal of Controlled Release, 2012
    Co-Authors: Takayuki Ishii, Tomohiro Asai, Dai Oyama, Tatsuya Fukuta, Nodoka Yasuda, Kosuke Shimizu, Tetsuo Minamino
    Abstract:

    Abstract Cerebral ischemia–reperfusion (I/R) injury induces secondary cerebral damage. As Drugs for treating this type of injury have shown poor efficacy and adverse side effects in clinical trials, a novel therapeutic strategy has been long awaited. In this study, we focused on the disruption of the blood–brain barrier after stroke, and applied a Liposomal Drug Delivery system (DDS) designed to enhance the pharmacological effect of the neuroprotectant and to avoid side effects. PEGylated liposomes were injected at varying time after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) model rats. The results showed PEGylated liposomes accumulated in the ischemic hemisphere at an early stage after reperfusion and were retained in the lesion for at least 24 h after injection. We also investigated the effectiveness of asialo-erythropoietin (AEPO)-modified PEGylated liposomes (AEPO-liposomes) in treating the cerebral I/R injury. AEPO-liposome treatment significantly reduced TTC-defined cerebral legion following cerebral I/R injury, and ameliorated motor function compared with vehicle and AEPO treatment. In conclusion, these results indicate that AEPO-liposomes are a promising Liposomal formulation for protecting the brain from I/R injury, and that this Liposomal DDS has potential as a novel strategy for the treatment of cerebral I/R injury.

  • Amelioration of cerebral ischemia–reperfusion injury based on Liposomal Drug Delivery system with asialo-erythropoietin
    Journal of Controlled Release, 2012
    Co-Authors: Takayuki Ishii, Tomohiro Asai, Dai Oyama, Tatsuya Fukuta, Nodoka Yasuda, Kosuke Shimizu, Tetsuo Minamino
    Abstract:

    Abstract Cerebral ischemia–reperfusion (I/R) injury induces secondary cerebral damage. As Drugs for treating this type of injury have shown poor efficacy and adverse side effects in clinical trials, a novel therapeutic strategy has been long awaited. In this study, we focused on the disruption of the blood–brain barrier after stroke, and applied a Liposomal Drug Delivery system (DDS) designed to enhance the pharmacological effect of the neuroprotectant and to avoid side effects. PEGylated liposomes were injected at varying time after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) model rats. The results showed PEGylated liposomes accumulated in the ischemic hemisphere at an early stage after reperfusion and were retained in the lesion for at least 24 h after injection. We also investigated the effectiveness of asialo-erythropoietin (AEPO)-modified PEGylated liposomes (AEPO-liposomes) in treating the cerebral I/R injury. AEPO-liposome treatment significantly reduced TTC-defined cerebral legion following cerebral I/R injury, and ameliorated motor function compared with vehicle and AEPO treatment. In conclusion, these results indicate that AEPO-liposomes are a promising Liposomal formulation for protecting the brain from I/R injury, and that this Liposomal DDS has potential as a novel strategy for the treatment of cerebral I/R injury.