Tuneable surface modification of PLGA nanoparticles carrying new antitubercular drug candidate

Biodegradable poly(lactic-co-glycolic acid)(PLGA 50:50) nanoparticles (NPs) were prepared and characterized in terms of size, composition, zeta potential and colloidal stability. Surface modification of PLGA NPs where primary amino groups were introduced to the Pluronic surface layer was developed. This method allows modulation of the charge character of the nanoparticle surface and provides functional groups for chemical reactions useful for targeting while retaining the aggregation stability of the system. The nanoparticles showed significant interaction with model membrane system (DPPC and DPPC + DPPG lipid layers) depending on the amount and type of Pluronic applied for stabilization of NPs. A new antitubercular drug candidate was encapsulated into the PLGA NPs. The cellular uptake and the intracellular efficacy against Mycobacterium tuberculosis (Mtb) of the drug and the drug loaded nano-particulate systems were investigated. These formulations were successfully taken up by MonoMac6 human monocyte cells and highly enhanced the availability and efficacy of the drug against Mtb which was demonstrated in comparative in vitro experiments. (C) 2014 Elsevier B.V. All rights reserved.