TLR2 agonistic lipopeptide enriched PLGA nanoparticles as combinatorial drug delivery vehicle

Abstract

The use of multiple Toll-Like Receptor (TLR) agonists as vaccine adjuvants has been proved to be beneficial against various diseases. Polymeric nanoparticles (Nps) provide wide range of options to incorporate multiple TLR agonists while ensuring optimal delivery and non-toxicity. To synergistically engage the cross-talk of TLR2 and TLR7, we synthesized pathogen mimicking Poly(lactic-co-glycolic acid) (PLGA) Nps encapsulating T7 (TLR7 agonist) and T2 lipopeptide (TLR2 agonist). The single emulsification-solvent evaporation process was employed for the synthesis where both hydrophobic T7 and TLR2 agonists were incorporated in a single step. Fourier Transform Infrared (FTIR) spectroscopy, Thermogravimetric (TGA) and Differential Scanning Calorimetry (DSC) analysis of pure PLGA and both agonists (T2 and T7) were compared with that of synthesized PLGA Nps to better understand the chemical bonding and stability. The physicochemical assessment was performed starting with particle size analysis and was confirmed using Transmission Electron Microscopy (TEM). During in-vitro release studies, about 40% of T7 was released for the first 5 hr followed by a two-day period of sustained release. Kinetics modelling results showed that the release kinetics was unaffected by the addition of T2 lipopeptide into PLGA Nps. These findings confirmed successful co-delivery of both agonists in same cargo that can be utilise to generate a balance immune response against various infectious diseases such as malaria, leishmania, hepatitis, influenza. The higher drug loading and the capability of PLGA suspension to get lyophilised paved the way for long-term storage, effective encapsulation, and co-delivery in vaccination.