کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1427736 986877 2006 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Enhancement of nasal absorption of large molecular weight compounds by combination of mucolytic agent and nonionic surfactant
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Enhancement of nasal absorption of large molecular weight compounds by combination of mucolytic agent and nonionic surfactant
چکیده انگلیسی

For improving the nasal absorption of poorly absorbable hydrophilic compounds, the suitability of a combination of a mucolytic agent, N-acetyl-l-cysteine (NAC), and a nonionic surfactant, polyoxyethylene (C25) lauryl ether (laureth-25), was examined. Rat studies with fluorescent isothiocyanate-labeled dextran (molecular weight ca. 4.4 kDa, FD-4) as a model hydrophilic compound revealed dramatic enhancement of nasal absorption when NAC and laureth-25 were simultaneously applied. The nasal bioavailability of FD-4 in saline solution was 8.2 ± 0.6% but increased to 40.0 ± 5.5% when 5% NAC and 5% laureth-25 were added. This synergistic enhancement could result from the mucolytic activity of NAC in reducing mucous viscosity by which the accessibilities of FD-4 and laureth-25 to the epithelial membrane were increased. Further rat studies proved that this formulation increased nasal absorption of salmon calcitonin. Absolute bioavailability from saline solution containing 5% NAC and 1% laureth-25 was 26.8 ± 2.2%, 3.5 times that of the commercial calcitonin nasal spray Miacalcin (7.7 ± 2.1%). The potential of the new formulation to cause tissue damage in terms of hemolytic activity and liberation of phospholipid from the nasal membranes was nil or slight. The combination of NAC and laureth-25 appears suitable for use in development of nasal products for poorly absorbable drugs, especially peptide and protein drugs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 110, Issue 2, 10 January 2006, Pages 347–352
نویسندگان
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