Tuneable surface modification of PLGA nanoparticles carrying new antitubercular drug candidate

Abstract

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 nanoparticulate 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.

Preparation and characterization of cationic Pluronic for surface modification and functionalization of polymeric drug delivery nanoparticles

“…Therefore we may expect that NPs containing Pluronic-amine surface layer show higher cellular uptake rate. This assumption was supported by our experimental data on drug loaded PLGA NPs [48]. When the carriers were functionalized by Pluronic F127 and Pluronic-F127-amine highly increased in vitro efficiency was achieved for an antituberculotic drug candidate.…”

“…When the Pluronic-amine derivative was used for the stabilization of the particles increased internalization and intracellular antibacterial effect was obtained. The presence of cationic charges on the particle surface was shown to increase the non-specific cell membrane affinity of the particles leading to increased cellular uptake rate [48].…”

Poly(ethylene carbonate)-containing polylactic acid microparticles with rifampicin improve drug delivery to macrophages

“…Mesoporous silica particles functionalised with polyethyleneimine or with a pH‐responsive nanovalve were used for delivery of RF and isoniazid, respectively . Polymeric nano‐ and microparticles containing RF and other drugs, with or without surface modification, have also shown to be taken up into macrophages …”

Polymeric nanoparticles: Recent development in synthesis and application

“…However, it was found that the hydrophobic character of the PLGA causes the nonspecific adsorption of plasma proteins directing to the uptake of the particles by the mononuclear phagocyte system and therefore their fast clearance from the body. It is recognized that this problem can be prevented if the particles are surface modified by the adsorption or grafting of hydrophilic polymers such as polyethylene glycol (PEG) or poly(ethylene oxide) (PEO) to improve its surface biocompatibility [83,84]. In 2016, Gyulai et al [83] with the aim to increase the potential of targeted drug delivery synthesized the end group derivative of Pluronics a promising drug carrier systems.…”