کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8414250 | 1545345 | 2014 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
N-alkylation of highly quaternized chitosan derivatives affects the paracellular permeation enhancement in bronchial epithelia in vitro
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کلمات کلیدی
Degree of quaternizationFD4FBSTMCFITCFCSHBSSCSLMHanks balanced salt solution - Hanks محلول نمک را تعویض می کندMTT - MTTN,N,N-Trimethyl chitosan - N، N، N-Trimethyl chitosantight junctions - اتصالات محکمPermeation enhancement - افزایش نفوذAli - اماTER - داشتنdegree of acetylation - درجه استیلاسیونDegree of substitution - درجه جایگزینیair–liquid interface - رابط هوا و مایعfetal bovine serum - سرم جنین گاوfetal calf serum - سرم گوساله جنینfluorescein isothiocyanate - فلوئورسین ایسوتیوسیاناتtransepithelial electrical resistance - مقاومت الکتریکی transepithelialConfocal scanning laser microscopy - میکروسکوپ لیزر اسکن کنفوکالApparent permeability - نفوذ پذیری ظاهریPapp - پاپChitosan - کیتوسان
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیوتکنولوژی یا زیستفناوری
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
This study describes the structure-activity relationship for carefully characterized N-alkyl-N-quaternary chitosan derivatives as permeation enhancers for drugs that are mainly absorbed through the paracellular pathway, such as macromolecular drugs and hydrophilic drugs, in a well defined bronchial epithelial cell line. The O-methyl free derivatives used in the study were fully trimethylated (100%) N,N,N-trimethyl chitosan (TMC) and N-propyl-(QuatPropyl), N-butyl-(QuatButyl) and N-hexyl (QuatHexyl)-N,N-dimethyl chitosan, with 85-91% degree of quaternization. The fully trimethylated TMC, from 0.25 mg/ml, decreased transepithelial electrical resistance (TER) in a reversible manner and enhanced the permeation of the macromolecule FITC-dextran 4 kDa (FD4) 2-5 fold. TMC did not cause any alterations in the tight junction (TJ) protein claudin-4 or in F-actin architecture. QuatHexyl was the most effective polymer to produce enhanced permeation and decreased TER from 0.016 mg/ml. Nevertheless, this enhanced permeation was accompanied by reduced viability and dissociation of F-actin and claudin-4 proteins. The structure-activity relationship suggests that more lipophilic derivatives show more permeation enhancement, TJ disassembly, and less viability in the order of hexyl â butyl > propyl > methyl and demonstrates that the permeation effect is not only mediated by permanent positive charge but also by the extent of N-alkylation. These results are relevant to elucidate the structural factors contributing to the permeation enhancement of chitosan derivatives and for potential use in pulmonary applications.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 86, Issue 1, January 2014, Pages 55-63
Journal: European Journal of Pharmaceutics and Biopharmaceutics - Volume 86, Issue 1, January 2014, Pages 55-63
نویسندگان
Berglind Eva Benediktsdóttir, Thórarinn Gudjónsson, Ãlafur Baldursson, Már Másson,