Polymeric Micelles Based on Modified Glycol Chitosan for Paclitaxel Delivery: Preparation, Characterization and...

Area of Science:

• Biomaterials Science
• Polymer Chemistry
• Drug Delivery Systems

Background:

• Glycol chitosan is a biocompatible polymer with potential in biomedical applications.
• Paclitaxel (PTX) is a potent chemotherapeutic agent with poor water solubility and significant toxicity issues with conventional delivery systems.
• Developing effective and safe delivery vehicles for hydrophobic drugs like PTX is crucial for improving therapeutic outcomes.

Purpose of the Study:

• To synthesize and characterize a novel amphiphilic polymer, α-tocopherol succinate modified glycol chitosan (TS-GC).
• To investigate the self-assembly properties of TS-GC into micelles and evaluate their potential as carriers for paclitaxel (PTX).
• To compare the in vitro and in vivo performance of PTX-loaded TS-GC micelles with a conventional Cremophor EL-based formulation.

Main Methods:

• Synthesis of TS-GC by conjugating α-tocopherol succinate to glycol chitosan.
• Characterization using Fourier-transform infrared (FT-FTIR) and proton nuclear magnetic resonance (¹H-NMR) spectroscopy.
• Micelle formation and characterization via critical aggregation concentration determination, Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), and X-ray Diffraction (XRD).
• In vitro and in vivo evaluation of paclitaxel-loaded TS-GC micelles compared to Cremophor EL formulation.

Main Results:

• TS-GC conjugates were successfully synthesized and characterized.
• TS-GC self-assembled into spherical micelles in aqueous solution with a critical aggregation concentration of 7.2 × 10⁻³ mg/mL.
• Paclitaxel-loaded TS-GC micelles exhibited an increased particle size (142 nm) compared to blank micelles (35 nm) with a slight decrease in zeta potential (+16 mV vs. +19 mV).
• XRD analysis indicated paclitaxel was in an amorphous or molecular state within the micelles.
• In vitro and in vivo studies demonstrated lower toxicity and enhanced drug delivery for PTX-loaded TS-GC micelles compared to the Cremophor EL formulation.

Conclusions:

• The synthesized TS-GC polymer effectively self-assembles into stable micelles suitable for drug encapsulation.
• PTX-loaded TS-GC micelles offer a promising alternative to conventional formulations, exhibiting improved safety and delivery profiles.
• TS-GC holds significant potential as a nanocarrier for enhancing the therapeutic efficacy of hydrophobic drugs like paclitaxel.