title: In vitro and in vivo evaluation of novel implantation technology in hydrogel contact lenses for controlled drug delivery.
abstract: 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 168h (NP 1:3 batch) with 150μg 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 192h. 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.
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India. Electronic address: furqanmpc@gmail.com.
authors: Furqan A
authors: FA
authors: Maulvi
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Dhara H
authors: DH
authors: Lakdawala
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Anjum A
authors: AA
authors: Shaikh
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Ankita R
authors: AR
authors: Desai
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Harsh H
authors: HH
authors: Choksi
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Rutvi J
authors: RJ
authors: Vaidya
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Ketan M
authors: KM
authors: Ranch
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Akshay R
authors: AR
authors: Koli
authors: Maliba Pharmacy College, Uka Tarsadia University, Surat 394350, India.
authors: Bhavin A
authors: BA
authors: Vyas
authors: Shah-Schulman Center for Surface Science and Nanotechnology, Dharmsinh Desai University, Nadiad 387001, India; Department of Chemical Engineering, University of Florida, Gainesville, FL 32611, United States; School of Earth and Environmental Sciences, Columbia University, New York, NY, United States; Department of Anaesthesiology, University of Florida, Gainesville, FL 32611, United States.
authors: Dinesh O
authors: DO
authors: Shah
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D003261:Contact Lenses; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000295:instrumentation; D004867:Equipment Design; D005260:Female; D005901:Glaucoma / Q000188:drug therapy* / Q000503:physiopathology; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits; D013999:Timolol / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D009883:Ophthalmic Solutions; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D013999:Timolol
keywords: Controlled drug delivery; Hydrogel contact lenses; Pharmacodynamic study; Pharmacokinetic study; Ring implantation; Timolol maleate