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Functional and pathological improvements of the hearts in diabetes model by the combined therapy of bFGF-loaded nanoparticles with ultrasound-targeted microbubble destruction
Journal article   Peer reviewed

Functional and pathological improvements of the hearts in diabetes model by the combined therapy of bFGF-loaded nanoparticles with ultrasound-targeted microbubble destruction

Ying-Zheng Zhao, Xin-Qiao Tian, Ming Zhang, Lu Cai, Ao Ru, Xiao-Tong Shen, Xi Jiang, Rong-Rong Jin, Lei Zheng, Kyle Hawkins, …
Journal of controlled release, v 186
28 Jul 2014
DOI: https://doi.org/10.1016/j.jconrel.2014.04.054
PMID: 24815422
Featured in Collection :   UN Sustainable Development Goals @ Drexel

Abstract

Animals Collagen - metabolism Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Experimental - pathology Diabetes Mellitus, Experimental - physiopathology Diabetic Cardiomyopathies - drug therapy Diabetic Cardiomyopathies - metabolism Diabetic Cardiomyopathies - pathology Diabetic Cardiomyopathies - physiopathology Fibroblast Growth Factor 2 - administration & dosage Fibroblast Growth Factor 2 - chemistry Heart - drug effects Heart - physiopathology Heparin - chemistry Microbubbles Myocardium - metabolism Myocardium - pathology Nanoparticles - administration & dosage Nanoparticles - chemistry Poloxamer - chemistry Rats, Sprague-Dawley Ultrasonics Ventricular Function, Left - drug effects
Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality among the diabetic patients and currently there is no effective means to reverse its pathological progress. Basic fibroblast growth factor (bFGF) has shown promise as a molecular therapy for DCM, but its delivery is inefficient and non-specific. In the present study, a therapy combining nanoparticle (NP) carrier and ultrasound-targeted microbubble destruction (UTMD) was reported the first time for bFGF delivery to the heart of diabetic rats. bFGF-loaded NP (bFGF-NP) were prepared with Poloxamer 188-grafted heparin copolymer using water-in-water technique, and the morphology, encapsulation efficiency, and bioactivity of bFGF-NP were studied. The cellular uptake and cytotoxicity of bFGF-NP were evaluated with primary cultures of the left ventricular (LV) cardiomyocytes in vitro. Therapeutic effects of bFGF-NP/UTMD on the heart of DCM rats were studied by measuring LV systolic and diastolic functions, hemodynamic characteristics and indicators of cardiac remodeling including myocardial collagen volume fraction and capillary density. Results demonstrated that bFGF-NP showed good round morphology, efficient bFGF encapsulation and stable bioactivity of bFGF in vitro. bFGF-NP/UTMD combined treatment significantly enhanced the efficiency of bFGF cellular uptake (P<0.05) without obvious cytotoxicity. Significant improvements (P<0.05) in both cardiac functions and tissue morphology in the DCM rats were observed in bFGF-NP/UTMD group. These were not achievable using free bFGF, bFGF-NP or UTMD treatment alone. Our results show that combining a non-viral vector with UTMD technique is an effective strategy to deliver bFGF to the heart, and the resulting growth factor therapy has demonstrated potential to reverse the progress of DCM by restoring the cardiac functions and even the structure of damaged cardiac tissues.

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42 citations in Web of Science
44 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Chemistry, Multidisciplinary
Pharmacology & Pharmacy
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