title: [Pyr1]-Apelin-13 delivery via nano-liposomal encapsulation attenuates pressure overload-induced cardiac dysfunction.
abstract: Nanoparticle-mediated sustained delivery of therapeutics is one of the highly effective and increasingly utilized applications of nanomedicine. Here, we report the development and application of a drug delivery system consisting of polyethylene glycol (PEG)-conjugated liposomal nanoparticles as an efficient in vivo delivery approach for [Pyr1]-apelin-13 polypeptide. Apelin is an adipokine that regulates a variety of biological functions including cardiac hypertrophy and hypertrophy-induced heart failure. The clinical use of apelin has been greatly impaired by its remarkably short half-life in circulation. Here, we investigate whether [Pyr1]-apelin-13 encapsulation in liposome nanocarriers, conjugated with PEG polymer on their surface, can prolong apelin stability in the blood stream and potentiate apelin beneficial effects in cardiac function. Atomic force microscopy and dynamic light scattering were used to assess the structure and size distribution of drug-laden nanoparticles. [Pyr1]-apelin-13 encapsulation in PEGylated liposomal nanocarriers resulted in sustained and extended drug release both in vitro and in vivo. Moreover, intraperitoneal injection of [Pyr1]-apelin-13 nanocarriers in a mouse model of pressure-overload induced heart failure demonstrated a sustainable long-term effect of [Pyr1]-apelin-13 in preventing cardiac dysfunction. We concluded that this engineered nanocarrier system can serve as a delivery platform for treating heart injuries through sustained bioavailability of cardioprotective therapeutics.
authors.affiliation: Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Vahid
authors.initials: V
authors.lastname: Serpooshan
authors.affiliation: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Senthilkumar
authors.initials: S
authors.lastname: Sivanesan
authors.affiliation: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Huang
authors.affiliation: Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA; Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Morteza
authors.initials: M
authors.lastname: Mahmoudi
authors.affiliation: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Malkovskiy
authors.affiliation: Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Inayathullah
authors.affiliation: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Wagh
authors.affiliation: Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Xuexiang J
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Metzler
authors.affiliation: Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Bernstein
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.affiliation: Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Pilar
authors.initials: P
authors.lastname: Ruiz-Lozano
authors.affiliation: Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA; Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: jayraja@stanford.edu.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Rajadas
mesh_terms: D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D008027:Light; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011312:Pressure; D012542:Scattering, Radiation
chemical_list: D004337:Drug Carriers; D036341:Intercellular Signaling Peptides and Proteins; D008081:Liposomes; C495199:apelin-13 peptide
keywords: Hypertrophy; Liposomal encapsulation; Nanocarrier; Sustained release; TAC; [Pyr1]-Apelin-13