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Positively charged liposomes containing tumor necrosis factor in solid tumors
1Department of Formulation Research, Pharmaceutical Research of Dainippon Pharmaceutical Co. Ltd., Fukushimaku, Osaka, Japan.
Biological & Pharmaceutical Bulletin
|March 22, 2000
Summary
Positively charged liposomes enhanced antitumor effects against solid tumors more than Tumor Necrosis Factor (TNF) solution. This novel drug delivery system reduced TNF toxicity, leading to complete tumor cures in some cases.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Solid tumors like Meth A sarcoma, MH-134 hepatoma, and colon 26 adenocarcinoma present treatment challenges.
- Tumor Necrosis Factor (TNF) has shown antitumor potential but is limited by systemic toxicity.
- Liposomes offer a promising drug delivery system for enhanced therapeutic efficacy and reduced side effects.
Purpose of the Study:
- To evaluate the antitumor efficacy of liposomes carrying Tumor Necrosis Factor (TNF) against solid tumors.
- To compare the effectiveness of positively charged liposomes versus negatively charged liposomes and free TNF solution.
- To assess the systemic toxicity and pharmacokinetic profile of TNF delivered via liposomes.
Main Methods:
- Intratumoral administration of liposomes and TNF solution in murine solid tumor models (Meth A sarcoma, MH-134 hepatoma, colon 26 adenocarcinoma).
- Comparison of antitumor effects between different liposome formulations (positively charged, negatively charged) and TNF solution.
- Measurement of TNF plasma concentration and calculation of Area Under Curve (AUC) to evaluate systemic exposure and toxicity.
Main Results:
- Liposomes demonstrated superior antitumor effects compared to TNF solution.
- Positively charged liposomes (decyl amine) showed enhanced efficacy over negatively charged liposomes and TNF solution.
- Positively charged liposomes significantly reduced systemic TNF exposure (AUC approximately 1/30 to 1/180 of TNF solution) and localized TNF retention.
- Reduced side effects allowed for higher TNF doses with positively charged liposomes, leading to complete tumor cures in some instances.
Conclusions:
- Positively charged liposomes represent an effective drug delivery system for enhancing TNF's antitumor activity against solid tumors.
- This liposomal formulation significantly improves therapeutic index by increasing local drug concentration and minimizing systemic toxicity.
- The enhanced efficacy and reduced toxicity of positively charged liposomes hold potential for complete tumor eradication.