2. Academic Validation
  3. [Pyr1]-Apelin-13 delivery via nano-liposomal encapsulation attenuates pressure overload-induced cardiac dysfunction

[Pyr1]-Apelin-13 delivery via nano-liposomal encapsulation attenuates pressure overload-induced cardiac dysfunction

  • Biomaterials. 2015 Jan;37:289-98. doi: 10.1016/j.biomaterials.2014.08.045.
Vahid Serpooshan 1,  Senthilkumar Sivanesan 2,  Xiaoran Huang 2,  Morteza Mahmoudi 3,  Andrey V Malkovskiy 2,  Mingming Zhao 4,  Mohammed Inayathullah 2,  Dhananjay Wagh 2,  Xuexiang J Zhang 2,  Scott Metzler 4,  Daniel Bernstein 1,  Joseph C Wu 5,  Pilar Ruiz-Lozano 1,  Jayakumar Rajadas 6
Affiliations

Affiliations

  • 1 Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2 Biomaterials and Advanced Drug Delivery Laboratory, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3 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.
  • 4 Stanford University, Department of Pediatrics, 300 Pasteur Dr., Stanford, CA 94305, USA.
  • 5 Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 6 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: [email protected].
PMID: 25443792 DOI: 10.1016/j.biomaterials.2014.08.045
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.

Keywords

Hypertrophy; Liposomal encapsulation; Nanocarrier; Sustained release; TAC; [Pyr1]-Apelin-13.

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