title: Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles improves ocular drug delivery.
abstract: In this work, a peptide for ocular delivery (POD) and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid) (PGLA)-polyethylene glycol (PEG)-nanoparticles (NPs) in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide); the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance) were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation in vitro (hen's egg test-chorioallantoic membrane assay) or in vivo (Draize test) was detected. Taken together, these data demonstrate that PLGA-PEG-POD NPs are promising vehicles for ocular drug delivery.
authors: Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, Institute for Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Barcelona, Spain.
authors: Aimee
authors: A
authors: Vasconcelos
authors: Department of Physical Chemistry, Institute of Nanoscience and Nanotechnology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: Estefania
authors: E
authors: Vega
authors: Nuclear Magnetic Resonance Unit, IQAC-CSIC, Barcelona, Spain.
authors: Yolanda
authors: Y
authors: Pérez
authors: Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, Institute for Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Barcelona, Spain.
authors: María J
authors: MJ
authors: Gómara
authors: Department of Physical Chemistry, Institute of Nanoscience and Nanotechnology, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.
authors: María Luisa
authors: ML
authors: García
authors: Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, Institute for Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Científicas (IQAC-CSIC), Barcelona, Spain.
authors: Isabel
authors: I
authors: Haro
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000737:chemistry; D051792:Basic Helix-Loop-Helix Proteins / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006016:Glycolates / Q000737:chemistry*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D006016:Glycolates; D019344:Lactic Acid; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011993:Recombinant Fusion Proteins; D000077022:Survivin; D054322:tat Gene Products, Human Immunodeficiency Virus; C512124:HIV-TAT-survivin (T34A) protein; C491825:TCF21 protein, human; C031149:glycolic acid
keywords: anti-inflammatory; controlled release; flurbiprofen; ocular tolerance; peptide for ocular delivery