Development of phosphorylated nanoparticles as zeta potential inverting systems

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery

Background:

• Overcoming physiological barriers like mucus and cell membranes is crucial for effective oral drug delivery.
• Developing smart nanoparticles that respond to specific biological cues can improve drug targeting and absorption.

Purpose of the Study:

• To engineer nanoparticles with a negative zeta potential that switches to positive upon encountering intestinal alkaline phosphatase.
• To assess the potential of these nanoparticles for navigating mucus and membrane barriers in drug delivery.

Main Methods:

• Modification of carboxymethyl cellulose and chitosan with phosphotyrosine using carbodiimide chemistry.
• Formation of polyelectrolyte complexes and characterization of nanoparticle size (200-300 nm) and initial zeta potential (-8 mV to -5 mV).
• In vitro evaluation of phosphate ion release and zeta potential changes using isolated phosphatase and a Caco-2 cell model.

Main Results:

• Demonstrated phosphate ion release from modified polymers and nanoparticles in the presence of intestinal alkaline phosphatase.
• Observed a significant shift in nanoparticle zeta potential from negative to positive (up to +8 mV) after phosphatase incubation.
• Resazurin assay confirmed the non-toxic nature of the polymers and nanoparticles.

Conclusions:

• The developed nanoparticles exhibit a stimuli-responsive charge-switching behavior, ideal for drug delivery.
• Their size and tunable surface charge facilitate overcoming mucus and membrane barriers.
• These non-toxic nanoparticles show promise as advanced tools for future drug delivery applications.