Journal
JOURNAL OF CONTROLLED RELEASE
Volume 264, Issue -, Pages 14-23Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2017.08.010
Keywords
Nanomedicine; Drug delivery; Complement activation; Pathway; Metastable liposome; Porcine model; Biophysics; Shear-responsive nano-container
Funding
- Swiss National Science Foundation (SNSF) via the National Research Program (NRP) 62 'Smart Materials' [126090]
- European Union Seventh Framework Programme [NMP-2012-LARGE-6-309820, 602923-2]
- 'Applied Materials and Nanotechnology Center of Excellence', Miskolc University
Ask authors/readers for more resources
Liposomes formulated from the 1,3-diamidophospholipid Pad-PC-Pad are shear-responsive and thus promising nano-containers to specifically release a vasodilator at stenotic arteries. The recommended preclinical safety tests for therapeutic liposomes of nanometer size include the in vitro assessment of complement activation and the evaluation of the associated risk of complement activation-related pseudo-allergy (CARPA) in vivo. For this reason, we measured complement activation by Pad-PC-Pad formulations in human and porcine sera, along with the nanopharmaceutical-mediated cardiopulmonary responses in pigs. The evaluated formulations comprised of Pad-PC-Pad liposomes, with and without polyethylene glycol on the surface of the liposomes, and nitroglycerin as a model vasodilator. The nitroglycerin incorporation efficiency ranged from 25% to 50%. In human sera, liposome formulations with 20 mg/mL phospholipid gave rise to complement activation, mainly via the alternative pathway, as reflected by the rises in SC5b-9 and Bb protein complex concentrations. Formulations having a factor of ten lower phospholipid content did not result in measurable complement activation. The weak complement activation induced by Pad-PC-Pad liposomal formulations was confirmed by the results obtained by performing an in vivo study in a porcine model, where hemodynamic parameters were monitored continuously. Our study suggests that, compared to FDA-approved liposomal drugs, Pad-PC-Pad exhibits less or similar risks of CARPA.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available