Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner.
Merve Seray UralMario Menéndez-MirandaGiuseppina SalzanoJeremie MathurinEce Neslihan AybekeAriane Deniset-BesseauAlexandre DazziMarianna PorcinoCharlotte Martineau-CorcosRuxandra GrefPublished in: Pharmaceutics (2021)
Vancomycin (VCM) is a last resort antibiotic in the treatment of severe Gram-positive infections. However, its administration is limited by several drawbacks such as: strong pH-dependent charge, tendency to aggregate, low bioavailability, and poor cellular uptake. These drawbacks were circumvented by engineering pH-responsive nanoparticles (NPs) capable to incorporate high VCM payload and deliver it specifically at slightly acidic pH corresponding to infection sites. Taking advantage of peculiar physicochemical properties of VCM, here we show how to incorporate VCM efficiently in biodegradable NPs made of poly(lactic-co-glycolic acid) and polylactic acid (co)polymers. The NPs were prepared by a simple and reproducible method, establishing strong electrostatic interactions between VCM and the (co)polymers' end groups. VCM payloads reached up to 25 wt%. The drug loading mechanism was investigated by solid state nuclear magnetic resonance spectroscopy. The engineered NPs were characterized by a set of advanced physicochemical methods, which allowed examining their morphology, internal structures, and chemical composition on an individual NP basis. The compartmentalized structure of NPs was evidenced by cryogenic transmission electronic microscopy, whereas the chemical composition of the NPs' top layers and core was obtained by electron microscopies associated with energy-dispersive X-ray spectroscopy. Noteworthy, atomic force microscopy coupled to infrared spectroscopy allowed mapping the drug location and gave semiquantitative information about the loadings of individual NPs. In addition, the NPs were stable upon storage and did not release the incorporated drug at neutral pH. Interestingly, a slight acidification of the medium induced a rapid VCM release. The compartmentalized NPs could find potential applications for controlled VCM release at an infected site with local acidic pH.
Keyphrases
- oxide nanoparticles
- high resolution
- atomic force microscopy
- single molecule
- drug delivery
- drug induced
- ionic liquid
- mass spectrometry
- magnetic resonance imaging
- emergency department
- staphylococcus aureus
- health information
- magnetic resonance
- single cell
- solar cells
- adverse drug
- high density
- combination therapy
- stress induced
- electron microscopy
- gram negative