title: Dorzolamide-loaded PLGA/vitamin E TPGS nanoparticles for glaucoma therapy: Pharmacoscintigraphy study and evaluation of extended ocular hypotensive effect in rabbits.
abstract: Poor drug penetration and rapid clearance after topical instillation of a drug formulation into the eyes are the major causes for the lower ocular bioavailability from conventional eye drops. Along with this, poor encapsulation efficiency of hydrophilic drug in polymeric nanoparticles remains a major formulation challenge. Taking this perspective into consideration, dorzolamide (DZ)-loaded PLGA nanoparticles were developed employing two different emulsifiers (PVA and vitamin E TPGS) and the effects of various formulation and process variables on particle size and encapsulation efficiency were assessed. Nanoparticles emulsified with vitamin E TPGS (DZ-T-NPs) were found to possess enhanced drug encapsulation (59.8±6.1%) as compared to those developed with PVA as emulsifier (DZ-P-NPs). Transcorneal permeation study revealed a significant enhancement in permeation (1.8-2.5 fold) as compared to solution. In addition, ex vivo biodistribution study showed a higher concentration of drug in the aqueous humour (1.5-2.3 fold). Histological and IR-camera studies proved the non-irritant potential of the formulations. Pharmacoscintigraphic studies revealed the reduced corneal clearance, as well as naso-lachrymal drainage in comparison to drug solution. Furthermore, efficacy study revealed that DZ-P-NPs and DZ-T-NPs significantly reduced the intraocular pressure by 22.81% and 29.12%, respectively, after a single topical instillation into the eye.
authors.affiliation: Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India. Electronic address: mhwarsi@gmail.com.
authors.forename: Musarrat H
authors.initials: MH
authors.lastname: Warsi
authors.affiliation: Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Anwar
authors.affiliation: Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Vaidehi
authors.initials: V
authors.lastname: Garg
authors.affiliation: Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Gaurav K
authors.initials: GK
authors.lastname: Jain
authors.affiliation: Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
authors.affiliation: Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India. Electronic address: farhanja_2000@yahoo.com.
authors.forename: Farhan J
authors.initials: FJ
authors.lastname: Ahmad
authors.affiliation: Nanoformulation Research Lab, Faculty of Pharmacy, Hamdard University, New Delhi, India; B. S. Anangpuria Institute of Pharmacy, Faridabad, Haryana, India.
authors.forename: Roop K
authors.initials: RK
authors.lastname: Khar
mesh_terms: D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005901:Glaucoma / Q000000981:diagnostic imaging / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D009798:Ocular Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D011877:Radionuclide Imaging; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014801:Vitamin A / Q000737:chemistry*; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D013449:Sulfonamides; D013876:Thiophenes; D014801:Vitamin A; D014810:Vitamin E; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C062765:dorzolamide; C014225:tocophersolan
keywords: Dorzolamide; Intraocular pressure; Ocular pharmacoscintigraphy; PLGA; Vitamin E TPGS