Development and evaluation of cationic surface-modified hydroxyapatite nanoparticles for enhanced membrane permeation

Area of Science:

• Materials Science
• Nanotechnology
• Biomedical Engineering

Background:

• Hydroxyapatite (HP) nanoparticles are biocompatible materials with potential in drug delivery.
• Modulating nanoparticle surface charge is crucial for enhancing interaction with biological membranes.
• Metronidazole is a key antimicrobial agent often requiring improved delivery systems.

Purpose of the Study:

• To develop positively charged metronidazole-loaded hydroxyapatite (MZ-HP) nanoparticles.
• To enhance membrane interaction, permeation, and therapeutic efficacy via surface charge modulation using cetyltrimethylammonium bromide (CT).

Main Methods:

• Synthesized mesoporous HP nanoparticles from eggshell-derived calcium oxide and loaded with metronidazole.
• Coated MZ-HP nanoparticles with CT (1-3.5 mM/g) via physisorption.
• Characterized nanoparticles using FTIR, XRD, SEM, TEM, and dynamic light scattering; assessed ex vivo skin permeation and in vitro cytocompatibility.

Main Results:

• Achieved maximum metronidazole loading efficiency of 87.2% with a drug to carrier ratio of 0.83 M:1 M.
• Successfully reversed surface charge from negative (HP, MZ-HP) to positive (+21.9 ± 3.3 mV) using CT.
• Demonstrated increased permeability flux (1.285 to 1.582 mg/h·cm²) and improved fibroblast tolerance (IC₅₀ = 184.9 ± 3.12 µg/mL) for CT-MZ-HP.

Conclusions:

• CT-coated MZ-HP nanoparticles represent an effective charge-modulated nanocarrier system.
• These nanoparticles exhibit enhanced trans-barrier transport, membrane interaction, and intracellular access.
• The developed system shows potential as a next-generation antimicrobial delivery platform with improved cytocompatibility.