کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513955 | 1556501 | 2017 | 27 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Impact of Chemical Structure on Conjunctival Drug Permeability: Adopting Porcine Conjunctiva and Cassette Dosing for Construction of In Silico Model
ترجمه فارسی عنوان
تأثیر ساختار شیمیایی بر نفوذپذیری داروهای مخدر: پذیرش کنجوکتیو گوشت خوک و دوز کاسه برای ساختن مدل سیلیکون
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کلمات کلیدی
PLSPSAHbdVIPPCA - PCAQSPR - برقراری ارتباط کمی بین ساختار و خواص مولکولhydrogen bond donor - تامین کننده هیدروژنPrincipal component analysis - تحلیل مولفههای اصلی یا PCAOphthalmic drug delivery - تحویل داروی OphthalmicAbsorption - جذبpartial least square - حداقل مربعات جزئیQuantitative structure-property relationship - رابطه ساختاری و مالکیت کمیPolar surface area - منطقه قطبیPermeability - نفوذپذیریMolecular weight - وزن مولکولی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
چکیده انگلیسی
Conjunctiva occupies most of the ocular surface area, and conjunctival permeability affects ocular and systemic drug absorption of topical ocular medications. Therefore, the aim of this study was to obtain a computational in silico model for structure-based prediction of conjunctival drug permeability. This was done by employing cassette dosing and quantitative structure-property relationship (QSPR) approach. Permeability studies were performed ex vivo across fresh porcine conjunctiva and simultaneous dosing of a cassette mixture composed of 32 clinically relevant drug molecules with wide chemical space. The apparent permeability values were obtained using drug concentrations that were quantified with liquid chromatography tandem-mass spectrometry. The experimental data were utilized for building a QSPR model for conjunctival permeability predictions. The conjunctival permeability values presented a 17-fold range (0.63-10.74 à 10â6 cm/s). The final QSPR had a Q2 value of 0.62 and predicted the external test set with a mean fold error of 1.34. The polar surface area, hydrogen bond donor, and halogen ratio were the most relevant descriptors for defining conjunctival permeability. This work presents for the first time a predictive QSPR model of conjunctival drug permeability and a comprehensive description on conjunctival isolation from the porcine eye. The model can be used for developing new ocular drugs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 9, September 2017, Pages 2463-2471
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 9, September 2017, Pages 2463-2471
نویسندگان
Eva Ramsay, Marika Ruponen, Théo Picardat, Unni Tengvall, Marjo Tuomainen, Seppo Auriola, Elisa Toropainen, Arto Urtti, Eva M. del Amo,