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Effects of polyamidoamine (PAMAM) dendrimers on the nasal absorption of poorly absorbable drugs in rats.

Abstract：

:The absorption enhancing effects of polyamidoamine (PAMAM) dendrimers with various concentrations and generations on the nasal absorption of fluorescein isothiocyanate-labeled dextran with an average molecular weight of 4400 (FD4) were initially studied in rats. PAMAM dendrimers with different generations improved the nasal absorption of FD4 and the absorption enhancing effects of PAMAM dendrimers were generation dependent. The rank order of absorption enhancement effects of PAMAM dendrimers was G3>G2>G1>G0. The absorption enhancing effects of PAMAM dendrimers were shown to be concentration dependent for the same generation of PAMAM dendrimers. The nasal membrane toxicity of these PAMAM dendrimers was evaluated by measuring the release of protein and lactate dehydrogenase (LDH) in nasal cavity lavage fluid. PAMAM dendrimers with higher generations and concentrations caused some membrane damage to the nasal tissues, but it was much less than the damage caused by sodium deoxycholate as a positive control. Based on the consideration between the efficacy and safety of PAMAM dendrimers, 1% (w/v) G3 dendrimer with high effectiveness and low toxicity was considered to be a best absorption enhancer for improving the nasal absorption of FD4. 1% (w/v) G3 dendrimer also improved the nasal absorption of macromolecular compounds and drugs including FD10, FD70, insulin and calcitonin. Finally, we measured the zeta potentials of drug solutions with or without PAMAM dendrimers to elucidate their absorption enhancing mechanisms. The zeta potentials of model drug solutions changed to positive by the addition of 1% (w/v) G3 dendrimer. This changing might trigger the absorption enhancing effects of PAMAM dendrimers on the nasal absorption of FDs, insulin and calcitonin, as the first step of mechanisms. In conclusion, 1% (w/v) G3 dendrimer is a promising absorption enhancer for improving the nasal absorption of FDs, insulin and calcitonin without any membrane damage to the nasal tissues.

journal_name

Int J Pharm

journal_title

International journal of pharmaceutics

authors

Dong Z,Katsumi H,Sakane T,Yamamoto A

doi

10.1016/j.ijpharm.2010.04.021

subject

Has Abstract

pub_date

2010-06-30 00:00:00

pages

244-52

issue

1-2

eissn

0378-5173

issn

1873-3476

pii

S0378-5173(10)00293-0

journal_volume

393

pub_type

杂志文章

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