Cationic Corona-Engineered Polymer-Lipid Hybrid Nanoparticles for Enhanced Dermal Penetration and Cellular...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmaceutics

Background:

• Conventional surfactants in drug delivery can cause cytotoxicity.
• Limitations exist in achieving both enhanced skin penetration and controlled drug release simultaneously.
• Novel nanocarrier systems are needed to overcome these challenges for effective transdermal drug delivery.

Purpose of the Study:

• To engineer cationic polymer-lipid hybrid nanoparticles (CLHNPs) for improved transdermal drug delivery.
• To overcome the cytotoxicity of conventional surfactants.
• To achieve enhanced skin penetration and controlled drug release.

Main Methods:

• Synthesis of poly(2-ethyl-2-oxazoline)-block-poly(ε-caprolactone) (POx-b-PCL) copolymers via ring-opening polymerization.
• Coassembly of copolymers with lecithin using nanoprecipitation to form CLHNPs (approx. 120 nm).
• Characterization using differential scanning calorimetry, NMR relaxometry, biolayer interferometry, confocal microscopy, and ex vivo skin penetration studies.

Main Results:

• CLHNPs exhibited increased core crystallinity and rigidity, leading to a 2-fold reduction in Higuchi release rate constants for sustained curcumin delivery.
• Demonstrated a 10-fold enhanced binding affinity to albumin via electrostatic interactions, correlating with improved cellular internalization in HaCaT keratinocytes.
• Confocal microscopy showed a 70% increase in transdermal penetration depth in ex vivo porcine skin (max fluorescence at 30-40 μm).

Conclusions:

• The developed CLHNPs offer a biocompatible platform for transdermal drug delivery.
• These nanoparticles synergistically combine controlled release kinetics with cationic surface properties.
• The system presents a promising approach for topical therapeutic applications, overcoming surfactant-related cytotoxicity.