Lipid-polymer hybrid nanoparticles with rhamnolipid-triggered release capabilities as anti-biofilm drug delivery vehicles

In lung biofilm infection therapies, the use of lipid-polymer hybrid nanoparticles to encapsulate drugs has emerged as a promising alternative to using liposomes because they have superior physicochemical stability and still possess the biofilm affinity and sputum-penetrating ability ofliposomes. To be deemed equally efficacious as liposomes against bacterial biofilms, however, the capability of hybrid nanoparticles to target-release encapsulated drugs at biofilm colonies must be demonstrated. This communication details our investigations into the trigger-release characteristics of hybrid nanoparticles in response to encountering rhamnolipids, which are ubiquitously present in biofilm colonies of Pseudomonas aeruginosa, a major respiratory pathogen. Poly（lactic-co-glycolic acid） and phospbatidylcholine were used as the poly- mer nanoparticle core and lipid coat, respectively. These investigations were performed using compounds from various biopharmaceutical classification systems （BCS） that differ in their lipid-membrane permeabilities. The release of BCS Class II1 compounds, which have poor lipid-membrane permeabilities, was successfully triggered by rhamnolipids at a concentration approximately equal to their clinically observed value, and this release was attributed to the disruption of lipid coats by rhamnolipid micelles. Not unexpectedly, BCS Class I compounds, which have high lipid-membrane permeabilities, were released freely whether or not rhamnolipids were present. The rate of the triggered release can be controlled by incor- porating an additional lipid layer on the hybrid nanoparticles via the electrostatically driven adsorption of lipid vesicles.

Ternary nanoparticle complex of ciprofloxacin exhibiting sustained release at gastric pH prepared by co-complexation with polyanions and an ionic amphiphile

Poor bioavailability of the broad spectrum antibiotic ciprofloxacin (CIP) is caused by its narrow absorption window in the stomach. With the aim of prolonging the gastric reside nee time of CIP, we prepared a ternary nano particle complex (nan oplex) of CIP by co-complexation w ith polya nions (sodium dextran sulfate (DXT)) and an anionic amphiphile (sodium dodecyl sulfate (SDS)). We investigated the effect of the charge ratio of DXT to SDS on the size, zeta potential, CIP payload, and CIP utilization rate of the CIP-DXTSDS nanoplex and its dissolution characteristics in simulated gastrointestinal fluids. Fourier transform infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry analyses showed that the ternary nanoplex was made up of amorphous C1P-DXT and crystalline CIP-SDS complexes. The size of the CIP-DXT-SDS nanoplex prepared at a >90% CIP utilization rate was 110-290 nm and it had a zeta potential of -16-39 mV, and CIP payload of 47-62%, depending on the charge ratio. At gastric pH, the CIP-DXT-SDS nanoplex prepared with a DXT:SDS charge ratio lower than 80:20 exhibited prolonged CIP release (60% dissolution after 8 h) compared with native CIP (100% dissolution after 1 h) and a binary CIP-DXT nanoplex (80% dissolution after 5 h), which was attributed to its lower solubility. The sustained release characteristics of the CIP-DXT-SDS nanoplex were comparable to those of existing CIP gastrorete ntive formulations.