Polyethylene glycol-complexed cationic liposome for enhanced cellular uptake and anticancer activity

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmaceutical Sciences

Background:

• Liposomes are effective drug carriers but suffer from short circulation times and low cellular uptake.
• The reticuloendothelial system (RES) rapidly clears conventional liposomes.
• Targeted delivery and enhanced intracellular uptake are crucial for improving therapeutic efficacy.

Purpose of the Study:

• To develop and characterize polyethylene glycol (PEG)-complexed cationic liposomes (PCL) for improved drug delivery.
• To evaluate the physicochemical properties, drug loading, cellular uptake, pharmacokinetics, and in vivo efficacy of PCL.
• To assess the potential of PCL as a drug delivery carrier for anticancer agents.

Main Methods:

• Cationic liposomes were complexed with carboxylated polyethylene glycol (mPEG-COOH) to form PCL.
• Particle size, zeta potential, and drug (doxorubicin) loading efficiency were determined.
• Intracellular uptake was assessed using flow cytometry and fluorescence microscopy.
• Pharmacokinetic studies in rats and in vivo antitumor activity against SKOV-3 ovarian adenocarcinoma xenografts were performed.

Main Results:

• PCL exhibited favorable particle size and zeta potential after PEG complexation.
• Doxorubicin loading efficiency into PCL was high (~96%).
• PCL demonstrated significantly higher intracellular uptake compared to Doxil and comparable in vitro cytotoxicity.
• In vivo studies showed comparable antitumor activity and slightly lower plasma drug levels for PCL versus Doxil.

Conclusions:

• PEG complexation via ionic interaction effectively modifies cationic liposomes, creating PCL.
• PCL exhibits enhanced cellular uptake and comparable in vivo efficacy to Doxil.
• PCL represents a promising drug delivery platform for enhancing the therapeutic potential of anticancer drugs.