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

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 5days 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.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

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

doi

10.1016/j.taap.2010.04.011

subject

Has Abstract

pub_date

2010-07-01 00:00:00

pages

83-90

issue

1-2

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(10)00138-9

journal_volume

246

pub_type

杂志文章

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