In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery

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• 作者：Furqan A. Maulvi^a ; ^{furqanmpc@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Dhara H. Lakdawala^a ; Anjum A. Shaikh^a ; Ankita R. Desai^a ; Harsh H. Choksi^a ; Rutvi J. Vaidya^a ; Ketan M. Ranch^a ; Akshay R. Koli^a ; Bhavin A. Vyas^a ; Dinesh O. Shah^b ; ^c ; ^d ; ^e
• 关键词：Timolol maleate ; Hydrogel contact lenses ; Ring implantation ; Controlled drug delivery ; Pharmacokinetic study ; Pharmacodynamic study
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 March 2016
• 年：2016
• 卷：226
• 期：Complete
• 页码：47-56
• 全文大小：2076 K

文摘

Glaucoma is commonly treated using eye drops, which is highly inefficient due to rapid clearance (low residence time) from ocular surface. Contact lenses are ideally suited for controlled drug delivery to cornea, but incorporation of any drug loaded particulate system (formulation) affect the optical and physical property of contact lenses. The objective of the present work was to implant timolol maleate (TM) loaded ethyl cellulose nanoparticle-laden ring in hydrogel contact lenses that could provide controlled drug delivery at therapeutic rates without compromising critical lens properties. TM-implant lenses were developed, by dispersing TM encapsulated ethyl cellulose nanoparticles in acrylate hydrogel (fabricated as ring implant) and implanted the same in hydrogel contact lenses (sandwich system). The TM-ethyl cellulose nanoparticles were prepared by double emulsion method at different ratios of TM to ethyl cellulose. The X-ray diffraction studies revealed the transformation of TM to amorphous state. In vitro release kinetic data showed sustained drug release within the therapeutic window for 168 h (NP 1:3 batch) with 150 μg loading. Cytotoxicity and ocular irritation study demonstrated the safety of TM-implant contact lenses. In vivo pharmacokinetic studies in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC), with TM-implant contact lenses in comparison to eye drop therapy. In vivo pharmacodynamic data in rabbit model showed sustained reduction in intra ocular pressure for 192 h. The study demonstrated the promising potential of implantation technology to treat glaucoma using contact lenses, and could serve as a platform for other ocular diseases.