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J Control Release. 2015 Feb 28;200:167-78. doi: 10.1016/j.jconrel.2015.01.008. Epub 2015 Jan 7.

A spatio-temporal cardiomyocyte targeted vector system for efficient delivery of therapeutic payloads to regress cardiac hypertrophy abating bystander effect.

Author information

1
Department of Zoology, University of Calcutta, 35, B.C. Road, Kolkata 700019, India.
2
Centre for Chemical Biology, Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500007, India.
3
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500007, India.
4
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India.
5
Division of Virology, National Institute of Cholera and Enteric Diseases, P-33, C.I.T. Road Scheme-XM, Beliaghata, Kolkata 700010, India.
6
Department of Zoology, University of Calcutta, 35, B.C. Road, Kolkata 700019, India. Electronic address: sagartirtha.sarkar@gmail.com.

Abstract

Diverse array of therapeutic regimens, drugs or siRNA, are commonly used to regress cardiac hypertrophy, although, bystander effect and lower retention of bioactive molecules significantly reduce their functional clinical efficacy. Carvedilol, a widely used and effective anti-hypertrophic drug, simultaneously blocks β-adrenergic receptors non-specifically in various organs. Likewise, non-specific genome-wide downregulation of p53 expression by specific siRNA efficiently abrogates cardiac hypertrophy but results in extensive tumorigenesis affecting bystander organs. Therefore, delivery of such therapeutics had been a challenge in treating cardiovascular dysfunction. Cardiac tissue engineering was successfully accomplished in this study, by encapsulating such bioactive molecules with a stearic acid modified Carboxymethyl chitosan (CMC) nanopolymer conjugated to a homing peptide for delivery to hypertrophied cardiomyocytes in vivo. The peptide precisely targeted cardiomyocytes while CMC served as the vector mediator to pathological myocardium. Controlled delivery of active therapeutic payloads within cardiomyocytes resulted in effective regression of cardiac hypertrophy. Thus, this novel nano-construct as a spatio-temporal vector would be a potential tool for developing effective therapeutic strategies within cardiac micro-environment via targeted knockdown of causal genes.

KEYWORDS:

Carboxy methyl chitosan; Cardiac tissue engineering; Cardiomyocyte; Drug delivery; Gene therapy

PMID:
25575863
DOI:
10.1016/j.jconrel.2015.01.008
[Indexed for MEDLINE]

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