title: Hyaluronic Acid Coated Albumin Nanoparticles for Targeted Peptide Delivery to the Retina.
abstract: Recent studies have shown that Connexin43 mimetic peptide (Cx43 MP) can prevent secondary damage following several retinal ischemic and inflammatory disorders by blocking the pathological opening of gap junction hemichannels. However, the poor stability of peptides and the presence of various intraocular barriers limit efficient retinal delivery in the clinical setting. The present study aimed to prolong the bioactivity of Cx43 MP and achieve targeted delivery to the retina by loading the peptide into hyaluronic acid (HA) coated human serum albumin nanoparticles (HSA NPs). Two different loading methods, adsorption and incorporation, were used with the peptide released slowly over a period of up to four months. Compared to uncoated particles, HA coated HSA NPs exhibited enhanced in vitro cellular uptake and ex vivo retinal penetration via HA-CD44 receptor mediated interactions. Furthermore, cell viability and Cx43 MP functionality assays showed that NPs protected Cx43 MP from degradation, sustained its release, and thus prolonged its bioactivity without reducing cell viability at concentrations used for Cx43 hemichannel blocking. Therefore, HA coated HSA NPs could have great potential for sustained and targeted delivery of Cx43 MP to treat various retinal inflammatory conditions.
authors.affiliation: Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland , Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Di
authors.initials: D
authors.lastname: Huang
authors.affiliation: Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland , Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Ying-Shan
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Buchanan Ocular Therapeutics Unit, Department of Ophthalmology, New Zealand National Eye Centre, Faculty of Medical and Health Sciences, The University of Auckland , Private Bag 92019, Auckland 1142, New Zealand.
authors.forename: Ilva D
authors.identifier: 0000-0001-5997-5994
authors.initials: ID
authors.lastname: Rupenthal
mesh_terms: D000418:Albumins / Q000008:administration & dosage* / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D058449:Intravitreal Injections / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry; D012160:Retina / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000418:Albumins; D018031:Connexin 43; D018960:Hyaluronan Receptors; D010455:Peptides; D006820:Hyaluronic Acid
keywords: connexin43; human serum albumin; hyaluronic acid; mimetic peptide; nanoparticles; retinal delivery