کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5550593 1557296 2017 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Parameters affecting the transscleral delivery of two positively charged proteins of comparable size
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی علوم دارویی
پیش نمایش صفحه اول مقاله
Parameters affecting the transscleral delivery of two positively charged proteins of comparable size
چکیده انگلیسی

Apart from molecular weight and net surface charge, there are other macromolecule-related factors that could, in principle, influence their diffusion across biological tissues, such as shape, conformability, water solubility and surface charge distribution.Lysozyme and cytochrome c, proteins with comparable molecular weight, isoelectric point and net surface charge in physiological conditions (approx. +7.8), are suitable model compounds for comparative studies, in particular to find out if other properties can have a role in the permeation across the sclera. The comparison between lysozyme and cytochrome c permeability was conducted by studying the permeation across the sclera and the choroid-Bruch's membrane and the diffusion across a hyaluronan gel-matrix. Melanin binding tests and the measurement of the electroosmosis flow during transscleral iontophoresis allowed for the evaluation of macromolecules affinity for the ocular tissues. Finally, anodal iontophoresis was applied to further confirm the interaction of the two proteins with the sclera.The data here collected show that two proteins with very similar MW, p Ka and charge can display very different diffusion properties across biological barriers. In particular, these differences can be attributed to a different interaction with specific components of ocular tissues: while the interaction with melanin and collagen fibers is apparently the same for the two molecules, a relevant difference was found in case of hyaluronic acid. Considering also literature evidences, the important parameters that can be responsible for this different affinity are molecular shape (spherical for cytochrome c vs prolate for lysozyme) and a combination of hydrophobic and electrostatic interactions that depends on the surface charge distribution. The interactions between sclera components and lysozyme are relatively strong and were not altered by the application of electric current.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Journal of Pharmaceutics - Volume 521, Issues 1–2, 15 April 2017, Pages 214-221
نویسندگان
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