Folate modified dual pH/reduction-responsive mixed micelles assembled using FA-PEG-PDEAEMA and PEG-SS-PCL for...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Polymer Chemistry

Background:

• Developing effective drug delivery systems is crucial for cancer therapy.
• Polymeric micelles offer potential for controlled drug release and targeted delivery.
• Stimuli-responsive materials enhance drug release at target sites.

Purpose of the Study:

• To design and synthesize folate-modified, dual pH/reduction-responsive mixed polymeric micelles for targeted doxorubicin delivery.
• To evaluate the drug loading, release kinetics, and in vitro cytotoxicity of these novel micelles.
• To investigate the potential of these micelles as an anticancer drug delivery platform.

Main Methods:

• Dissipative particle dynamics (DPD) simulations for micelle assembly.
• Synthesis and characterization of polymers (PEG-PDEAEMA, FA-PEG-PDEAEMA, PEG-SS-PCL) using NMR, FT-IR, GPC.
• Preparation and evaluation of doxorubicin (DOX)-loaded mixed micelles (MIX1 and MIX2).
• In vitro drug release studies at different pH and reduction conditions.
• Cytotoxicity assays on HepG2 cells.

Main Results:

• Mixed micelles (MIX1) achieved high drug loading (20.22% LC, 50.69% EE) and efficient doxorubicin encapsulation.
• Controlled release profiles observed, with accelerated release under acidic and reductive conditions (pH 5.0 + 10 mM DTT).
• Folate-modified micelles (MIX1) exhibited enhanced cytotoxicity against HepG2 cells compared to free DOX and non-modified micelles (MIX2).
• Blank micelles demonstrated good biocompatibility.

Conclusions:

• Folate-modified dual pH/reduction-responsive mixed polymeric micelles are effective for high-capacity, controlled doxorubicin delivery.
• The targeted delivery and stimuli-responsive release enhance anticancer efficacy.
• These micelles represent a promising candidate for targeted cancer therapy.