Phosphatase-degradable nanoparticles providing sustained drug release

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Development of novel drug delivery systems is crucial for improving therapeutic efficacy.
• Enzyme-responsive materials offer targeted drug release mechanisms.
• Polyphosphate nanoparticles present a promising platform for drug encapsulation.

Purpose of the Study:

• To engineer enzyme-degradable polyphosphate nanoparticles (NPs) for sustained release of ethacridine (ETH).
• To investigate the impact of divalent metal cations (calcium, zinc, iron) on NP properties and drug release.
• To evaluate the antibacterial efficacy of released ETH.

Main Methods:

• Synthesis of calcium, zinc, and iron polyphosphate NPs via co-precipitation with ETH.
• Characterization of NPs for size, PDI, zeta potential, encapsulation efficiency, and drug loading.
• Assessment of NP toxicity using hemolysis and cell viability assays.
• Evaluation of enzymatic degradation by alkaline phosphatase (ALP) and subsequent drug release.
• Determination of antibacterial activity against Escherichia coli.

Main Results:

• Synthesized NPs ranged from 300-480 nm with negative zeta potentials and high encapsulation efficiencies (83.73%-95.99%).
• NPs demonstrated good hemocompatibility, with concentration-dependent effects on HEK-293 cell viability.
• Calcium and zinc polyphosphate NPs showed significant changes in zeta potential, particle size, and drug release upon ALP treatment.
• Released ETH from Ca- and Zn-PP NPs retained potent antibacterial activity against E. coli.

Conclusions:

• Polyphosphate nanoparticles cross-linked with divalent cations offer a viable strategy for sustained drug delivery.
• ALP-triggered drug release from these nanocarriers holds potential for parenteral administration.
• The developed NPs demonstrate promise for targeted antibacterial therapy.