Fabrication and Optimization of Poly(ε-caprolactone) Microspheres Loaded with S-Nitroso-N-Acetylpenicillamine for Nitric Oxide Delivery

Author:

Alvi Syed Baseeruddin1,Pracha Nooruddin1,Shalaan Mahmoud1,Dholaniya Pankaj Singh12,Mergaye Muhamad1,Sridharan Divya1ORCID,Khan Mahmood134ORCID

Affiliation:

1. Division of Basic and Translational Research, Department of Emergency Medicine, The Ohio State University, Columbus, OH 43210, USA

2. Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India

3. Department of Physiology and Cell Biology, The Ohio State University, Columbus, OH 43210, USA

4. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA

Abstract

Heart disease is one of the leading causes of death in the United States and throughout the world. While there are different techniques for reducing or preventing the impact of heart disease, nitric oxide (NO) is administered as nitroglycerin for reversing angina or chest pain. Unfortunately, due to its gaseous and short-lived half-life, NO can be difficult to study or even administer. Therefore, controlled delivery of NO is desirable for therapeutic use. In the current study, the goal was to fabricate NO-releasing microspheres (MSs) using a donor molecule, S-Nitroso-N-Acetyl penicillamine, (SNAP), and encapsulating it in poly(ε-caprolactone) (PCL) using a single-emulsion technique that can provide sustained delivery of NO to cells over time without posing any toxicity risks. Optimization of the fabrication process was performed by varying the duration of homogenization (5, 10, and 20 min) and its effect on entrapment efficiency and size. The optimized SNAP-MS had an entrapment efficiency of ˃50%. Furthermore, we developed a modified method for NO detection by using NO microsensors to detect the NO release from SNAP-MSs in real time, showing sustained release behavior. The fabricated SNAP-MSs were tested for biocompatibility with HUVECs (human umbilical vein endothelial cells), which were found to be biocompatible. Lastly, we tested the effect of controlled NO delivery to human induced pluripotent stem-derived cardiomyocytes (hiPSC-CMs) via SNAP-MSs, which showed a significant improvement in the electrophysiological parameters and alleviated anoxic stress.

Funder

National Institute of Health

OSU start-up funds

American Heart Association Undergraduate Research Fellowship

American Heart Association post-doctoral fellowship

Publisher

MDPI AG

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