Erythrocyte membrane coated biodegradable nanoparticles detoxify LPS-induced toxicity by producing non-mutagenic metabolites and downregulating pro-inflammatory cytokines and oxidative stress markers.

Bacterial lipopolysaccharides are considered as chief virulent factor and found to be responsible for numerous clinical manifestations and lethal effects in both animals and humans. The ability of LPS to express acute phase proteins and cytokines leads to pathological effects. The study was designed to optimize biomimetic and biodegradable nanoparticles (NPs) based regimen for detoxification of LPS induced toxicity. The surface of NPs was modified with freshly collected red blood cells (RBCs) membranes and polyethylene glycol. Endotoxins were extracted from LPS using E.coli and Salmonella typhi. Chitosan NPs diameter & zeta potential was 78.8 nm & +28.3 mV, while after coating with RBCs membrane and PEG, the size was 712.4,712 nm and potential as + 40 and + 28.6 mV respectively. Albino rats were given endotoxin insult following NPs treatment. There was significant decrease in pyrexia after treatment with coated nanoparticles (98.7 ± 1.23 °F for LPS E. coli & RBCs coated NPs group while 99.7 ± 0.75 °F for LPS salmonella + RBCs coated NPs group). A significant reduction in WBCs count was noted after treatment with RBCs coated NPs, in both LPS E.coli and LPS Salmonella i.e. 11.7 ± 1.2 count/cmm and 11.3 ± 1.1 in comparison to LPS E. coli and LPS Salmonella treated group (17.5 ± 0.9 and 16.8 ± 2.3 count/cmm respectively in comparison to healthy control (12 ± 0.7 count/cmm). A significant reduction was observed in CAT and SOD concentration, after treatment with LPS E. coli and Salmonella treatments i.e. 21.9 ± 1.6, 21.9 ± 1.81 and 21.6 ± 2, and 21.6 ± 2.07 µg/mg protein respectively in comparison to healthy control i.e. 32.7 ± 1.7 & 32.2 ± 1.3 µg/mg protein. There was significant improvement after administration of RBCs coated NPs as the recorded values were 31.1 ± 1.36 and 31.7 ± 1.43 µg/mg protein for LPS E. coli & LPS salmonella respectively. The same pattern was observed for SOD after treatment with RBCs coated NPs (LPS E. coli 31 ± 0.7 µg/mg protein and LPS salmonella 31.2 ± 0.8 µg/mg protein. The similar pattern was observed for pro-inflammatory cytokines level. Histopathological studies also showed significant decrease in morbidity after treatment. Results were analyzed statistically by ANOVA followed by Tukey's test. It is concluded that RBCs membrane coated NPs have great potential for detoxification of LPS derived endotoxins and thus may reduce the morbidity. However, further studies are required for safety and dose optimization of NPs.