Lipid-Polymer Hybrid Nanoparticles for Enhanced Anti-Infective Delivery

A recent study demonstrated that dual core-shell LPHNPs can co-deliver cefotaxime and an antimicrobial peptide (RN7IN6), preserving both payloads' activity and improving in vitro Gram-negative potency.

The formulation pairs a chitosan-based polymeric inner core loaded with cefotaxime (CTX) and a bacteria-relevant lipid shell incorporating RN7IN6, yielding uniformly nanosized particles with low polydispersity and physicochemical changes consistent with effective shell coverage. Encapsulation efficiencies for RN7IN6 trended ~10-18% across loading concentrations while CTX incorporation remained stable. Peptide activity assays indicated preserved antimicrobial function after encapsulation, supporting potential localized pharmacodynamic advantages from co-delivery.

In vitro efficacy screens against Escherichia coli provided the strongest signals: CTX in LPHNPs registered an MIC around 0.25 μg/mL, empty LPHNPs had an MIC of 2 μg/mL, and co-loaded LPHNPs produced complete inhibition at the lowest tested combination (0.375 μg/mL CTX with 0.25 μg/mL RN7IN6). RN7IN6 within co-loaded particles showed at least a 21-fold improvement in MIC relative to the free combination in this organism. These preclinical efficacy signals support prioritizing in vivo efficacy testing and selection of appropriate Gram-negative infection models.

The team manufactured the formulation using microfluidic mixing, which enabled controlled mixing, reproducible nanoscale size distributions, and continuous processing potential. Optimization identified a total flow rate near 20 mL/min, a lipid concentration of ≈0.5 mg/mL, and a flow-rate ratio of ~5:1 as conditions that produced small, uniform LPHNPs and reproducible coating of polymer cores with the lipid shell—providing a credible pathway toward scalable manufacture while practical hurdles remain.