Phosphatase-degradable nanoparticles providing sustained drug release

Abstract

AimThe study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine (ETH). MethodsCalcium polyphosphate (Ca-PP), zinc polyphosphate (Zn-PP) and iron polyphosphate nanoparticles (Fe-PP NPs) were prepared by co-precipitation of sodium polyphosphate with cations and ETH. Developed nanocarriers were characterized regarding particle size, PDI, zeta potential, encapsulation efficiency and drug loading. Toxicological profile of nanocarriers was assessed via hemolysis assay and cell viability on human blood erythrocytes and HEK-293 cells, respectively. The enzymatic degradation of NPs was evaluated in presence of alkaline phosphatase (ALP) monitoring the release of monophosphate, shift in zeta potential and particle size as well as drug release. The antibacterial efficacy against Escherichia coli was determined via microdilution assay. ResultsNPs were obtained in a size range between 300 – 480 nm displaying negative zeta potential values. Encapsulation efficiency was in the range of 83.73 %– 95.99 %. Hemolysis assay underlined sufficient compatibility of NPs with blood cells, whereas drug and NPs showed a concentration dependent effect on HEK-293 cells viability. Ca- and Zn-PP NPs exhibited remarkable changes in zeta potential, particle size, monophosphate and drug release upon incubation with ALP, compared to Fe-PP NPs showing only minor differences. The released ETH from Ca- and Zn-PP nanocarriers retained the antibacterial activity against E. coli, whereas no antibacterial effect was observed with Fe-PP NPs. ConclusionPolyphosphate nanoparticles cross-linked with divalent cations and ETH hold promise for sustained drug delivery triggered by ALP for parental administration.