A simple way to enhance Doxil® therapy: Drug release from liposomes at the tumor site by amphiphilic block copolymer

Abstract

The antitumor efficacy of Doxil® is hindered by the poor release of the active drug from the liposome at the tumor sites. This study investigates a possibility to enhance drug release from the liposomes and increase therapeutic efficacy of Doxil® by administering Pluronic block copolymers once the liposomal drug accumulates in the tumor sites. In our study, the fluorescence de-quenching experiments were designed to investigate the drug release from liposome by Pluronic P85. MTT cytotoxicity assay and confocal microscopy images were carried out to determine whether Pluronic P85 could facilitate release of Dox from Doxil®. Anti-tumor growth and distribution of drug were evaluated when Pluronic P85 was injected 1 hr, 48 hrs, or 96 hrs after the Doxil® administration in A2780 human ovarian cancer xenografts. Addition of Pluronic P85 resulted in release of Dox from the liposomes accompanied with significant increases of Dox delivery and cytotoxic effect in cancer cells. The greatest anti-tumor effect of single injection of Doxil® was achieved when Pluronic P85 was administered 48 hrs after Doxil®. The Confocal tile scanning images of tumor section showed that copolymer treatment induced the release of the drug in the tumors from the vessels regions to the bulk of the tumor. No release of the drug remaining in circulation was observed. Our study has demonstrated a simple approach for localized release of Dox from liposome by Pluronic P85 at the tumor site, which was therapeutically beneficial.

Self-Assembled Monomethoxy (Polyethylene Glycol)-<I>b</I>-<I>P</I>(<I>D</I>,<I>L</I>-Lactic-<I>co</I>-Glycolic Acid)-<I>b</I>-<I>P</I>(<I>L</I>-Glutamic Acid) Hybrid-Core Nanoparticles for Intracellular pH-Triggered Release of Doxorubicin

“…The drug-loaded nanoparticles exhibited smaller particle sizes and were stable in physiological media. For these drug-loaded nanoparticles, no significant initial release was observed within 24 hours and no very slow release like that of Doxil ® (10% within 7 day), 45 was observed in pH7.4PBS. Importantly, the DOX release from the nanoparticles was significantly accelerated in pH5.0 acetate buffer due to destruction of the nanoparticles.…”

“…33 34 When DOX was encapsulated in the hybrid core of nanoparticles, its self-fluorescence was quenched compared with that of the free drug. 35 The influence of HSA on drug leakage was examined in a fluorescence de-quenching experiment and results are illustrated in Figure 7(B). The fluorescence intensity of drug-loaded nanoparticles increased after incubation with HSA at 37 C for 6 hours, which suggested drug leakage from the nanoparticles.…”

Humid Heat Autoclaving of Hybrid Nanoparticles Achieved by Decreased Nanoparticle Concentration and Improved Nanoparticle Stability Using Medium Chain Triglycerides as a Modifier

“…Using the self-fluorescence quenching property of doxorubicin (DOX) (32,33), cargo leakage during autoclaving was investigated by monitoring the changes in the fluorescence spectra of free DOX in pristine/autoclaved samples (Fig. 5a).…”

Radio Frequency-Activated Nanoliposomes for Controlled Combination Drug Delivery

“…Since the release of hydrophilic drugs encapsulated in the liposomal core is typically driven by passive diffusion, the insertion of stabilizing PL chains into the bilayers may hinder this process (16)(17)(18). The enhanced rigidity of the bilayer that could be imparted by the inclusion of hydrophobic drugs might likewise stabilize the systems and reduce the drug release rate.…”