Journal Article

The Effect of Polymeric Nanoparticles on Biocompatibility of Carrier Red Blood Cells

Vargas-Morales, Omayra, Zern, Blaine, Pan, Daniel, Mitragotri, Samir, Muzykantov, Vladimir, Anselmo, Aaron C., Gupta, Vivek, Zakrewsky, Michael

2016

Overview

Red blood cells (RBCs) can be used for vascular delivery of encapsulated or surface-bound drugs and carriers. Coupling to RBC prolongs circulation of nanoparticles (NP, 200 nm spheres, a conventional model of polymeric drug delivery carrier) enabling their transfer to the pulmonary vasculature without provoking overt RBC elimination. However, little is known about more subtle and potentially harmful effects of drugs and drug carriers on RBCs. Here we devised high-throughput in vitro assays to determine the sensitivity of loaded RBCs to osmotic stress and other damaging insults that they may encounter in vivo (e.g. mechanical, oxidative and complement insults). Sensitivity of these tests is inversely proportional to RBC concentration in suspension and our results suggest that mouse RBCs are more sensitive to damaging factors than human RBCs. Loading RBCs by NP at 1:50 ratio did not affect RBCs, while 10-50 fold higher NP load accentuated RBC damage by mechanical, osmotic and oxidative stress. This extensive loading of RBC by NP also leads to RBCs agglutination in buffer; however, addition of albumin diminished this effect. These results provide a template for analyses of the effects of diverse cargoes loaded on carrier RBCs and indicate that: i) RBCs can tolerate carriage of NP at doses providing loading of millions of nanoparticles per microliter of blood; ii) tests using protein-free buffers and mouse RBCs may overestimate adversity that may be encountered in humans.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Agglutination / Albumins - administration & dosage / Albumins - chemistry / Analysis / Animals / Biocompatibility / Biocompatible Materials - chemistry / Bioengineering / Biology and Life Sciences / Blood / Blood & organ donations / Blood cells / Buffers / Care and treatment / Chemical engineering / Damage / Drug carriers / Drug Carriers - chemistry / Drug delivery / Drug delivery systems / Drug Delivery Systems - methods / Drugs / Engineering and Technology / Erythrocyte Count - methods / Erythrocytes / Erythrocytes - chemistry / Erythrocytes - metabolism / Humidity / In vivo methods and tests / Laboratory animals / Male / Medicine / Medicine and Health Sciences / Mice / Nanoparticles / Nanoparticles - chemistry / Osmotic stress / Oxidative stress / Pharmacology / Physical Sciences / Polymers / Polymers - chemistry / Red blood cells / Research and Analysis Methods / Sensitivity / Sensitivity and Specificity / Studies