Lignin nanoparticles as a novel carrier for efficacious delivery of toll like receptor 7/8 agonist: Physicochemical and in-vitro evaluation |
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| Institution: | 1. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160 014, India;2. Department of Chemistry and Centre of Advanced Studies, Panjab University, Chandigarh, 160 014, India;3. Vaxine Pty Ltd, Warradale, Australia;4. College of Medicine and Public Health, Flinders University, Adelaide, Australia;5. National Interdisciplinary Centre of Vaccine, Immunotherapeutics and Antimicrobials, Panjab University, Chandigarh, 160 014, India;1. Aryabhatta Centre for Nanoscience & Nanotechnology, Aryabhatta Knowledge University, Patna, 800001, India;2. Dept. of Zoology, A N College, Patna and Dept. of Education, Govt. of Bihar, India;1. Department of Chemistry, Faculty of Sciences, Aydin Adnan Menderes University, 09010, Aydin, Turkey;2. Department of Physics, Faculty of Sciences, Aydin Adnan Menderes University, 09010, Aydin, Turkey;3. Technical Sciences Vocational School, Gazi University, Ostim, Ankara, 06374, Turkey;1. Department of Chemistry, Sardar Vallabhai National Institute of Technology, Surat, 395007, Gujarat, India;2. Department of Chemistry, School of Advanced Sciences, VIT-AP University, Amaravati, 522237, Andhra Pradesh, India;3. Department of Polymer Science & Technology, Sri Krishnadevaraya University, Ananthapuramu, 515003, Andhra Pradesh, India;1. Department of Physics, Federal University of Health Sciences, Otukpo, Benue State, Nigeria;2. Operations Unit, Starsight Energy, Nigeria;3. Centre for Satellite Technology Development-NASRDA, Abuja, Nigeria;4. Department of Physics, Rivers State University, Port Harcourt, Rivers State, Nigeria |
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| Abstract: | 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-imidazo4,5-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 ∼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 β value ≤ 0.75 corresponding to Fickian diffusion. Moreover, blank as well as meta-aminomethyl BBIQ-loaded LNPs were non-hemolytic 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. |
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| Keywords: | Lignin Toll-like receptor Vaccine adjuvant Drug delivery system Biopolymer |
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