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A safety and tolerability study of differently-charged nanoparticles for local pulmonary drug delivery

 
: Harush-Frenkel, O.; Bivas-Benita, M.; Nassar, T.; Springer, C.; Sherman, Y.; Avital, A.; Altschuler, Y.; Borlak, J.; Benita, S.

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Toxicology and Applied Pharmacology 246 (2010), Nr.1-2, S.83-90
ISSN: 0041-008X
Englisch
Zeitschriftenaufsatz
Fraunhofer ITEM ()
PEG-PLA; safety; anionic; cationic; surface charge; tolerability; pulmonary; nanoparticle

Abstract
Nanoparticle (NP) based drug delivery systems provide promising opportunities in the treatment of lung diseases. Here we examined the safety and tolerability of pulmonary delivered NPs consisting of PEG-PLA as a function of particle surface charge. The rationale for such a comparison should be attributed to the differential pulmonary toxicity of positively and negatively charged PEG-PLA NP. Thus, the local and systemic effects of pulmonary administered NPs were investigated following 5 days of daily endotracheal instillation to BALB/c mice that were euthanized on the eighth or nineteenth day of the experiment. We collected bronchoalveolar lavages and studied hematological as well as histochemistry parameters. Notably, the cationic stearylamine based PEG-PLA NPs elicited increased local and systemic toxic effects both on the eighth and nineteenth day. In contrast, anionic NPs of similar size were much better tolerated with local inflammatory effects observed only on the eighth experimental day after pulmonary instillation. No systemic toxicity effect was observed although a moderate change was noted in the platelet count that was not considered to be of clinical significance. No pathological observations were detected in the internal organs following instillation of anionic NPs. Overall these observations suggest that anionic PEG-PLA NPs are useful pulmonary drug carriers that should be considered as a promising therapeutic drug delivery system.

: http://publica.fraunhofer.de/dokumente/N-149030.html