Lignin nanoparticles as a novel carrier for efficacious delivery of toll like receptor 7/8 agonist: Physicochemical and in-vitro evaluation

Imidazoquinolinone (IMDQ) derivatives are known TLR7/8 agonists and are approved by the FDA for antiviral and skin cancer treatment. Their use as innate immune system activating molecules has been limited by poor pharmacokinetic properties and toxicities associated with systemic administration. In the present study, an IMDQ derivative, 1-(3-(aminomethyl) benzyl)-2-butyl-1H-imidazo[4,5-c] quinolin-4-amine (meta-aminomethyl BBIQ, 4), was encapsulated in biopolymer lignin nanoparticles (LNPs) to develop slow-release delivery system and to enhance its immune activating properties. A co-precipitation method was used to synthesize LNPs of alkali lignin. Characterization studies demonstrated the formation of spherical shaped nanoparticles of similar to 150 nm size. The encapsulation efficiency and loading capacity for meta-aminomethyl BBIQ in LNPs was found to be 99% and 70%, respectively. In-vitro release studies showed 78% release over 24 h at pH 7.4 followed by sustained release. Kinetic modelling studies showed the release profile followed Weibull order kinetics with beta value <= 0.75 corresponding to Fickian diffusion. Moreover, blank as well as meta-aminomethyl BBIQ-loaded LNPs were nonhemolytic and did not show significant cytotoxicity in RAW 264.7 and MDA-MB-23 cells at all tested concentrations. This study confirms the potential to use LNPs as a drug delivery system for immune modulators or vaccine adjuvants.

Automated summary

In this study, an IMDQ derivative, meta-aminomethyl BBIQ, was encapsulated in biopolymer lignin nanoparticles (LNPs) to develop a slow-release delivery system and enhance its immune activating properties. The formation of spherical shaped LNPs of approximately 150 nm size was confirmed, and the release of meta-aminomethyl BBIQ from LNPs followed sustained release kinetics. The study suggests the potential use of LNPs as a drug delivery system for immune modulators or vaccine adjuvants.