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Gemcitabine delivery to pancreatic ductal adenocarcinoma is limited by poor pharmacokinetics, dense fibrosis and hypo-vascularization. Activatable liposomes, with drug release resulting from local heating, enhance serum stability and circulation, and the released drug retains the ability to diffuse within the tumor. A limitation of liposomal gemcitabine has been the low loading efficiency. To address this limitation, we used the superior solubilizing potential of copper (II) gluconate to form a complex with gemcitabine at copper:gemcitabine (1:4). Thermosensitive liposomes composed of
DSPE-PEG2k (80:15:5, mole%) then reached 12 wt% loading, 4-fold greater than previously reported values. Cryo transmission electron microscopy confirmed the presence of a liquid crystalline gemcitabine‑copper mixture. The optimized gemcitabine liposomes released 60% and 80% of the gemcitabine within 1 and 5 min, respectively, at 42 °C. Liposomal encapsulation resulted in a circulation half-life of ~2 h in vivo (compared to reported circulation of 16 min for free gemcitabine in mice), and free drug was not detected within the plasma. The resulting gemcitabine liposomes were efficacious against both murine breast cancer and pancreatic cancer in vitro. Three repeated treatments of activatable gemcitabine liposomes plus ultrasound hyperthermia regressed or eliminated tumors in the neu deletion model of murine breast cancer with limited toxicity, enhancing survival when compared to treatment with gemcitabine alone. With 5% of the free gemcitabine dose (5 rather than 100 mg/kg), tumor growth was suppressed to the same degree as gemcitabine. Additionally, in a more aggressive tumor model of murine pancreatic cancer, liposomal gemcitabine combined with local hyperthermia induced cell death and regions of apoptosis and necrosis.
This article was published in the following journal.
Name: Journal of controlled release : official journal of the Controlled Release Society
The co-encapsulation of paclitaxel (PTX) and doxorubicin (DXR) in liposomes has the potential to offer pharmacokinetic and pharmacodynamic advantages, providing delivery of both drugs to the tumor at ...
: SLC6A14 (ATB), a Na/Clcoupled transporter for neutral/cationic amino acids, is overexpressed in many cancers; It has been investigated as a target for improved liposomal drug delivery to treat liver...
Nitrogen mustard (NM) was among the earliest drugs used to treat malignant tumors, and it kills tumor cells by cross-linking DNA. Unfortunately, because of the short half-life and unfavorable selectiv...
Nanotechnology has recently gained lots of interest in drug delivery due to its potential to improve the therapeutic outcomes of various diseases. Particularly, a wide range of different nano-sized ve...
Mannose Receptor (MR) and DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) are two mannose-specific targets for antigens carried by liposomes but DC-SIGN is more specific ...
Background: Site-specific delivery of anti-cancer therapeutics is paramount for both reducing nonspecific toxicities and increasing efficacy of chemotherapeutic agents. Due to their small ...
RATIONALE: Drugs used in chemotherapy, such as gemcitabine and flavopiridol, use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug ...
RATIONALE: Drugs used in chemotherapy, such as gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. GTI-2040 may stop the growth of tumor cell...
RATIONALE: Drugs used in chemotherapy, such as PR-104, docetaxel, and gemcitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them...
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Ph...
Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins.
Forms to which substances are incorporated to improve the delivery and the effectiveness of drugs. Drug carriers are used in drug-delivery systems such as the controlled-release technology to prolong in vivo drug actions, decrease drug metabolism, and reduce drug toxicity. Carriers are also used in designs to increase the effectiveness of drug delivery to the target sites of pharmacological actions. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
Carbohydrate antigen most commonly seen in tumors of the ovary and occasionally seen in breast, kidney, and gastrointestinal tract tumors and normal tissue. CA 125 is clearly tumor-associated but not tumor-specific.
A tumor necrosis factor receptor subtype with specificity for TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 15. It is found in tissues containing LYMPHOCYTES and may play a role in regulating lymphocyte homeostasis and APOPTOSIS. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...
Clinical Approvals Clinical Trials Drug Approvals Drug Delivery Drug Discovery Generics Drugs Prescription Drugs In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are dis...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...