Author(s): Dobrovolskaia MA
Assorted challenges in physicochemical characterization, sterilization, depyrogenation, and in the assessment of pharmacology, safety, and efficacy profiles accompany pre-clinical development of nanotechnology-formulated drugs. Some of these challenges are not unique to nanotechnology and are common in the development of other pharmaceutical products. However, nanoparticle-formulated drugs are biochemically sophisticated, which causes their translation into the clinic to be particularly complex. An understanding of both the immune compatibility of nanoformulations and their effects on hematological parameters is now recognized as an important step in the (pre)clinical development of nanomedicines. An evaluation of nanoparticle immunotoxicity is usually performed as a part of a traditional toxicological assessment; however, it often requires additional in vitro and in vivo specialized immuno- and hematotoxicity tests. Herein, I review literature examples and share the experience with the NCI Nanotechnology Characterization Laboratory assay cascade used in the early (discovery-level) phase of pre-clinical development to summarize common challenges in the immunotoxicological assessment of nanomaterials, highlight considerations and discuss solutions to overcome problems that commonly slow or halt the translation of nanoparticle-formulated drugs toward clinical trials. Special attention will be paid to the grand-challenge related to detection, quantification and removal of endotoxin from nanoformulations, and practical considerations related to this challenge.
Referred From: https://doi.org/10.1016/j.jconrel.2015.08.056
Author(s): Chin KL, Anis FZ, Sarmiento ME, Norazmi MN, Acosta A, et al.
Author(s): Negishi H, Taniguchi T, Yanai H
Author(s): Di Franco S, Turdo A, Todaro M, Stassi G
Author(s): Bessis N, GarciaCozar FJ, Boissier MC
Author(s): Sakurai H, Kawabata K, Sakurai F, Nakagawa S, Mizuguchi H, et al.
Author(s): Burel SA, Machemer T, Ragone FL, Kato H, Cauntay P, et al.
Author(s): Lennox KA, Behlke MA
Author(s): Leeds JM, Henry SP, Geary R, Burckin T, Levin AA, et al.
Author(s): Behlke MA
Author(s): Jacobi AM, Rettig GR, Turk R, Collingwood MA, Zeiner SA, et al.
Author(s): Neun BW, Dobrovolskaia MA
Author(s): Neun BW, Dobrovolskaia MA
Author(s): Potter TM, Neun BW, Rodriguez JC, Ilinskaya AN, Dobrovolskaia MA, et al.
Author(s): Fennrich S, Hennig U, Toliashvili L, Schlensak C, Wendel HP, et al.
Author(s): Coch C, Luck C, Schwickart A, Putschli B, Renn M, et al.
Author(s): Daneshian M, Von Aulock S, Hartung T
Author(s): Hasiwa N, Daneshian M, Bruegger P, Fennrich S, Hochadel A, et al.
Author(s): Hoffmann S, Peterbauer A, Schindler S, Fennrich S, Poole S, et al.
Author(s): Vessillier S, Eastwood D, Fox B, Sathish J, Sethu S, et al.
Author(s): Alvarez-Salas LM
Author(s): Henry SP, Geary RS, Yu R, Levin AA
Author(s): Holmlund JT, Monia BP, Kwoh TJ, Dorr FA
Author(s): Monteith DK, Henry SP, Howard RB, Flournoy S, Levin AA, et al.
Author(s): Evans DC, Watt AP, Nicoll-Griffith DA, Baillie TA
Author(s): Keefe AD, Pai S, Ellington A
Author(s): Schmidt A, Schwerd T, Hamm W, Hellmuth JC, Cui S, et al.