Polyborane-encapsulated PEGylated Liposomes Prepared Using Post-insertion Technique for Boron Neutron Capture Therapy

Area of Science:

• Nanomedicine
• Biotechnology
• Radiotherapy

Background:

• PEGylated liposomes are effective boron carriers for Boron Neutron Capture Therapy (BNCT).
• A post-insertion method for adding polyethylene glycol (PEG) to liposomes after formation has been reported.
• Optimizing PEGylated liposome preparation is crucial for enhancing BNCT efficacy and cost-effectiveness.

Purpose of the Study:

• To prepare and evaluate polyborane-encapsulated PEGylated liposomes for BNCT using a post-insertion technique (post-PEG liposomes).
• To compare the physicochemical properties, in vitro cytotoxicity, cell uptake, and in vivo biodistribution of post-PEG liposomes with conventionally prepared PEGylated liposomes (pre-PEG liposomes).
• To determine if the post-insertion technique can achieve similar therapeutic effects with reduced DSPE-PEG amounts.

Main Methods:

• Preparation of polyborane-encapsulated PEGylated liposomes using conventional (pre-PEG) and post-insertion (post-PEG) methods with varying DSPE-PEG concentrations.
• Characterization of liposome physicochemical properties: particle size distribution, surface charge density, and fixed aqueous layer thickness.
• In vitro evaluation: cytotoxicity assays and cell uptake studies using B16 melanoma and RAW264.7 cells.
• In vivo biodistribution studies in tumor-bearing mice, measuring boron concentration and tumor/blood ratios at 24 hours post-administration.

Main Results:

• Post-PEG liposomes and pre-PEG liposomes exhibited equivalent particle size distributions, surface charge densities, and fixed aqueous layer thicknesses.
• In vitro studies confirmed that post-PEG liposomes and pre-PEG liposomes had similar effects regarding cytotoxicity and cell uptake.
• In vivo biodistribution studies showed comparable boron concentrations (73.2-77.6 µg/g) and tumor/blood ratios (5.5-5.8) for both types of PEGylated liposomes.
• The post-insertion technique successfully produced effective BNCT liposomes using half the amount of DSPE-PEG compared to the conventional method.

Conclusions:

• The post-insertion technique is a viable method for preparing PEGylated liposomes for BNCT.
• This technique allows for the creation of effective boron carriers with a reduced DSPE-PEG content, potentially lowering production costs.
• Post-PEG liposomes demonstrate comparable physicochemical, in vitro, and in vivo properties to conventionally prepared pre-PEG liposomes, validating their utility in BNCT.