Advertisement

Topics

Heat-activated drug delivery increases tumor accumulation of synergistic chemotherapies.

08:00 EDT 10th June 2019 | BioPortfolio

Summary of "Heat-activated drug delivery increases tumor accumulation of synergistic chemotherapies."

Doxorubicin is a clinically important anthracycline chemotherapeutic agent that is used to treat many cancers. Nanomedicine formulations including Doxil® and ThermoDox® have been developed to mitigate doxorubicin cardiotoxicity. Doxil is used clinically to treat ovarian cancer, AIDS-related Kaposi's sarcoma, and multiple myeloma, but there is evidence that therapeutic efficacy is hampered by lack of drug release. ThermoDox is a lipid-based heat-activated formulation of doxorubicin that relies on externally applied energy to increase tissue temperatures and efficiently trigger drug release, thereby affording therapeutic advantages compared to Doxil. However, elevating tissue temperatures is a complex treatment process requiring significant time, cost, and expertise compared to standard intravenous chemotherapy. This work endeavors to develop a companion therapeutic to ThermoDox that also relies on heat-triggered release in order to increase the therapeutic index of doxorubicin. To this end, a thermosensitive liposome formulation of the heat shock protein 90 inhibitor alvespimycin has been developed and characterized. This research demonstrates that both doxorubicin and alvespimycin are potent anti-cancer agents and that heat amplifies their cytotoxic effects. Furthermore, the two drugs are proven to act synergistically when cancer cells are treated with the drugs in combination. The formulation of alvespimycin was rationally designed to exhibit similar pharmacokinetics and drug release kinetics compared to ThermoDox, enabling the two drugs to be delivered to heated tumors at similar efficiencies resulting in control of a particular synergistic ratio of drugs. In vivo measurements demonstrated effective heat-mediated triggering of doxorubicin and alvespimycin release from thermosensitive liposomes within tumor vasculature. This treatment strategy resulted in a ~10-fold increase in drug concentration within tumors compared to free drug administered without tumor heating.

Affiliation

Journal Details

This article was published in the following journal.

Name: Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Pages:

Links

DeepDyve research library

PubMed Articles [23405 Associated PubMed Articles listed on BioPortfolio]

Ratiometric co-encapsulation and co-delivery of doxorubicin and paclitaxel by tumor-targeted lipodisks for combination therapy of breast cancer.

Combination therapy is a promising treatment for certain advanced drug-resistant cancers. Although effective inhibition of various tumor cells was reported in vitro, combination treatment requires imp...

Depletion of collagen by losartan to improve tumor accumulation and therapeutic efficacy of photodynamic nanoplatforms.

Nanocarriers for drug delivery have made great progress in the treatment of cancer, but the dense extracellular collagen of tumors has greatly limited the efficiency of drug delivery. In this study, l...

A biomimetic cascade nanoreactor for tumor targeted starvation therapy-amplified chemotherapy.

Targeted drug delivery with precisely controlled drug release and activation is highly demanding and challenging for tumor precision therapy. Herein, a biomimetic cascade nanoreactor (designated as Me...

Acidity/Reducibility Dual-Responsive Hollow Mesoporous Organosilica Nanoplatforms for Tumor-Specific Self-Assembly and Synergistic Therapy.

Featured with large surface area, uniform interpenetrating mesopores, diverse organic framework hybridization, and well-defined surface properties, the hollow mesoporous organosilica nanoparticle (HMO...

Multi-stimuli responsive nanosystem modified by tumor-targeted carbon dots for chemophototherapy synergistic therapy.

In this work, a tumor-targeted and multi-stimuli responsive drug delivery system combining infrared thermal imaging of cells with thermo-chemotherapy was developed. Oxidized mesoporous carbon nanopart...

Clinical Trials [11716 Associated Clinical Trials listed on BioPortfolio]

Fentanyl Transdermal Matrix Patch ZR-02-01 Applied With CHADD™ (Controlled Heat-Assisted Drug Delivery) to Treat Breakthrough Pain in Patients With Moderate to Severe Non-Malignant Chronic Pain

A multi-center study to evaluate the efficacy of CHADD (Controlled Heat-Assisted Drug Delivery) applied over a 50 mcg/hr ZR-02-01 matrix transdermal fentanyl patch for the treatment of bre...

Phase I/II Trial of Doxil and Hyperthermia for Breast Cancer Patients With Chest Wall Recurrence or Stage IV Disease With Locally Advanced Breast Cancer

Purpose: The purpose of this protocol is to evaluate the combination of Doxil chemotherapy and heat treatment for recurrent breast cancer located on the chestwall following mastectomy. T...

Impact of Thermal Stress on Pulmonary Absorption and Toxicokinetics of 3 Organic Solvents

In Quebec, thousands of workers are concomitantly exposed to heat and chemical compounds. Exposure to heat induces physiological responses that help maintaining a stable body temperature. ...

Treatment of Tumors in the Urinary Collecting System of the Kidney or Ureter Using a Light Activated Drug (WST11)

The purpose of this study is to test the safety of a combination of the study drug called WST11 and PDT. Photodynamic therapy (PDT) is a type of ablation therapy (treatment which destroys ...

Heat-Activated Target Therapy of Local-Regional Relapse in Breast Cancer Patients

The 105-15-201 study is designed to assess the effectiveness and tolerability of the combination of heat-activated target therapy (radiotherapy + hyperthermia + lyso-thermosensitive liposo...

Medical and Biotech [MESH] Definitions

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.

Systems for the delivery of drugs to target sites of pharmacological actions. Technologies employed include those concerning drug preparation, route of administration, site targeting, metabolism, and toxicity.

The application, via IMPLANTED ELECTRODES, of short bursts of electrical energy in the radiofrequency range, interspersed with pauses in delivery of the current long enough to dissipate the generated heat and avoid heat-induced tissue necrosis.

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.

A potent inhibitor of ADENOSINE DEAMINASE. The drug induces APOPTOSIS of LYMPHOCYTES, and is used in the treatment of many lymphoproliferative malignancies, particularly HAIRY CELL LEUKEMIA. It is also synergistic with some other antineoplastic agents and has immunosuppressive activity.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Drug Delivery
<!--LGfEGNT2Lhm-->Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals.  <!--LGfEGNT2Lhm-->Drug delivery technologies are <!--LGfEGNT2Lhm-->patent pr...

Women's Health
Women's Health - key topics include breast cancer, pregnancy, menopause, stroke Follow and track Women's Health News on BioPortfolio: Women's Health News RSS Women'...


Searches Linking to this Article