title: Nanoparticle-Based Topical Ophthalmic Gel Formulation for Sustained Release of Hydrocortisone Butyrate.
abstract: This study was conducted to develop formulations of hydrocortisone butyrate (HB)-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (PLGA NP) suspended in thermosensitive gel to improve ocular bioavailability of HB for the treatment of bacterial corneal keratitis. PLGA NP with different surfactants such as polyvinyl alcohol (PVA), pluronic F-108, and chitosan were prepared using oil-in-water (O/W) emulsion evaporation technique. NP were characterized with respect to particle size, entrapment efficiency, polydispersity, drug loading, surface morphology, zeta potential, and crystallinity. In vitro release of HB from NP showed a biphasic release pattern with an initial burst phase followed by a sustained phase. Such burst effect was completely eliminated when nanoparticles were suspended in thermosensitive gels and zero-order release kinetics was observed. In HCEC cell line, chitosan-emulsified NP showed the highest cellular uptake efficiency over PVA- and pluronic-emulsified NP (59.09 ± 6.21%, 55.74 ± 6.26%, and 62.54 ± 3.30%, respectively) after 4 h. However, chitosan-emulsified NP indicated significant cytotoxicity of 200 and 500 μg/mL after 48 h, while PVA- and pluronic-emulsified NP exhibited no significant cytotoxicity. PLGA NP dispersed in thermosensitive gels can be considered as a promising drug delivery system for the treatment of anterior eye diseases.
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA.
authors.forename: Hoang M
authors.initials: HM
authors.lastname: Trinh
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA.
authors.forename: Vibhuti
authors.initials: V
authors.lastname: Agrahari
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Sheng
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Pal
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte Street, Kansas City, Missouri, 64108, USA. mitraa@umkc.edu.
authors.forename: Ashim K
authors.initials: AK
authors.lastname: Mitra
mesh_terms: D060433:Administration, Ophthalmic; D000287:Administration, Topical; D001682:Biological Availability; D002460:Cell Line; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D060527:Corneal Keratocytes / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry; D005128:Eye Diseases / Q000188:drug therapy; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D065587:Ocular Absorption; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004655:Emulsions; D005782:Gels; C007975:hydrocortisone-17-butyrate; D020442:Poloxamer; D011142:Polyvinyl Alcohol; D048271:Chitosan; D006854:Hydrocortisone
keywords: PLGA nanoparticles; hydrocortisone butyrate; thermosensitive gel; topical administration