title: Design of an anti-inflammatory composite nanosystem and evaluation of its potential for ocular drug delivery.
abstract: This study compared two specific embodiments of an ocular nanosystem (NS): one portraying a purely polymeric system, referred to as the chitosan-poly(ε-caprolactone) nanosystem, and the other based on a composite lipoidal-polymeric NS architecture utilizing phospholipids-the lipoidal-chitosan-poly(ε-caprolactone) nanosystem. Investigations undertaken were implicit to warrant inclusion in an implantable system for the intelligent treatment of inflammatory disorders (specifically ocular afflictions). Results obtained highlighted the enhanced efficacy of both NS to an indomethacin suspension in terms of tissue permeation, cell uptake, and anti-inflammatory activity. Furthermore, the size (134.3 vs. 140.7 nm); surface charge (+49.4 vs. +55.7 mV); drug incorporation efficiency (75.00% vs. 67.20%); flux across the retinal pigment epithelium-choroid-sclera (0.002951 vs. 0.001255 mg cm (-2) h(-1) ); anti-inflammatory efficacy, demonstrated by a decrease in 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole complex formation (0.0031 vs. 0.0023 mmol L(-1) ) and decrease in NFκB formation (decrease in relative optical density of 0.2027 vs. 0.2420); and enhanced inflammatory cell uptake, visualized via high-speed fluorescence and confocal microscopy, all highlighted the enhanced potential of the lipoidal system compared with the purely polymeric NS for potentially targeting inflammatory disorders of the posterior segment of the eye. Mechanics energy relationships revealed the favorable hydrophilic-lipophilic balance of the composite NS compared with the purely polymeric NS.
authors.affiliation: Department of Pharmacy and Pharmacology, University of the Witwatersrand, Parktown, Johannesburg 2193, South Africa.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Du Toit
authors.forename: Thirumala
authors.initials: T
authors.lastname: Govender
authors.forename: Trevor
authors.initials: T
authors.lastname: Carmichael
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D018938:Caco-2 Cells; D048271:Chitosan / Q000031:analogs & derivatives*; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D005123:Eye / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008081:Liposomes / Q000737:chemistry; D008958:Models, Molecular; D016328:NF-kappa B / Q000276:immunology; D049329:Nanostructures / Q000737:chemistry / Q000648:ultrastructure; D010743:Phospholipids / Q000737:chemistry; D011091:Polyesters / Q000737:chemistry*; D011817:Rabbits
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D008081:Liposomes; D016328:NF-kappa B; D010743:Phospholipids; D011091:Polyesters; C016240:polycaprolactone; D048271:Chitosan; D007213:Indomethacin
keywords: ELISA; cell uptake; computational modeling; confocal microscopy; lipids; liposomes; permeation; nanoparticles; nanotechnology; ophthalmic drug delivery