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Related Concept Videos

Bioavailability Enhancement: Drug Permeability Enhancement01:27

Bioavailability Enhancement: Drug Permeability Enhancement

After oral administration, poor permeability often limits the rate at which drugs are absorbed through the intestinal epithelium. Enhancing drug permeability is crucial for effective therapy, and several strategies have been developed to overcome this challenge.One effective strategy involves the use of lipid-based formulations. These formulations enhance dissolution and solubility, targeting physiological mechanisms to increase drug absorption. This includes stimulating bile salt secretion,...
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Factors Affecting Dissolution: Drug Permeability, Stability and Stereochemistry

Orally administered drugs primarily enter the systemic circulation via passive diffusion through the intestinal membranes. The drug's absorption is influenced by drug stability in the gastrointestinal GI tract, membrane permeability, the surface area available for absorption, luminal drug concentration, and residence time in the lumen. Drug permeability can be enhanced by adjusting the lipophilicity, polarity, or molecular size of the drug, promoting its passive transport across intestinal...

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Custom-designed Laser-based Heating Apparatus for Triggered Release of Cisplatin from Thermosensitive Liposomes with Magnetic Resonance Image Guidance
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Optimizing Liposomal Cisplatin Efficacy through Membrane Composition Manipulations.

Natalia Zisman1, Nancy Dos Santos, Sharon Johnstone

  • 1Department of Preformulation, Celator Pharmaceuticals Corp., 1779 West 75th Avenue, Vancouver, BC, Canada V6P 6P2.

Chemotherapy Research and Practice
|February 8, 2012
PubMed
Summary
This summary is machine-generated.

Optimizing liposomal cisplatin delivery requires balancing drug release rates. An intermediate release formulation demonstrated the greatest antitumor activity in preclinical models, highlighting the importance of controlled drug release for enhanced efficacy.

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Area of Science:

  • Pharmacology
  • Drug Delivery Systems
  • Oncology

Background:

  • The first clinically evaluated liposomal cisplatin (SPI-077) showed tumor accumulation but lacked efficacy, potentially due to poor drug release.
  • Optimizing liposomal formulations is crucial for improving cisplatin's therapeutic index.

Purpose of the Study:

  • To investigate the relationship between cisplatin release rate from liposomes and antitumor efficacy.
  • To identify an optimal liposomal formulation for enhanced cisplatin delivery and activity.

Main Methods:

  • Liposomal formulations with varying phospholipid content (C18 and C16) were created to modulate membrane fluidity and drug release.
  • Formulations were evaluated in the P388 murine leukemia model for drug release kinetics, plasma half-life, and antitumor activity.

Main Results:

  • Formulations with high phase transition temperatures (T(m)) exhibited poor drug release and low efficacy.
  • Formulations with very low T(m) showed rapid drug release in plasma, limiting tumor delivery and efficacy.
  • An intermediate release formulation (DSPC:DPPC:DSPG:Chol, 35:35:20:10) with an 8.3-hour cisplatin plasma half-life demonstrated the highest antitumor activity.

Conclusions:

  • Liposomal cisplatin release rate is a critical factor in determining formulation efficacy.
  • Controlled drug release is essential for effective cisplatin delivery to tumors.
  • This study provides insights into designing optimized liposomal cisplatin formulations for cancer therapy.