Trans-scleral iontophoretic delivery of low molecular weight therapeutics

JOURNAL OF CONTROLLED RELEASE

卷:147

Article

Guengoer, Sevgi¹  Delgado-Charro, M. Begona¹  Ruiz-Perez, Begona²  Schubert, William²  Isom, Phil²  Moslemy, Peyman²  Patane, Michael A.²  Guy, Richard H.¹ 

[1] Univ Bath, Sch Pharm & Pharmacol, Bath BA2 7AY, Avon, England

[2] Eyegate Pharmaceut Inc, Waltham, MA 02453 USA

关键词: Ocular iontophoresis;    Trans-scleral;    Timolol;    Dexamethasone phosphate;    Vancomycin;   

DOI  :  10.1016/j.jconrel.2010.07.107

来源: Elsevier

【 摘 要 】

The fundamental understanding of ocular drug delivery using iontophoresis is not at the same level as that for transdermal electrotransport. Research has therefore been undertaken to characterise the electrical properties of the sclera (charge, permselectivity, and isoelectric point (pI)) and to determine the basics of iontophoretic transport of model neutral, cationic, and anionic species (respectively, mannitol, timolol, and dexamethasone phosphate). Like the skin, the sclera supports a net negative charge under physiological pH conditions and has a pI between 3.5 and 4. Equally, the principles of trans-scleral iontophoretic transport of low molecular weight compounds are consistent with those observed for skin. Iontophoretic delivery of timolol and dexamethasone phosphate was proportional to applied current and drug concentration, and trans-scleral iontophoresis in rabbits led to enhanced intraocular levels of these compounds compared to passive delivery. The behaviour of higher molecular weight species such as peptide drugs and other biopharmaceuticals (e.g., proteins and oligonucleotides) has not been fully characterised. Further work has been undertaken, therefore, to examine the trans-scleral iontophoresis of vancomycin, a glycopeptide antibiotic with a relatively high molecular weight of 1448 Da. It was indeed possible to deliver vancomycin by iontophoresis but trans-scleral transport did not increase linearly with either increasing current density or peptide concentration. (C) 2010 Elsevier B.V. All rights reserved.

【 授权许可】

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