Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents

Radhakrishnan, Krishna and Thomas, Midhun B and Pulakkat, Sreeranjini and Gnanadhas, Divya P and Chakravortty, Dipshikha and Raichur, Ashok M (2016) Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents. In: JOURNAL OF NANOPARTICLE RESEARCH, 17 (8).

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Abstract

Enzyme-and pH-responsive polyelectrolyte nanocapsules having diameters in the range of 200 +/- 20 nm were fabricated by means of Layer-by-Layer assembly of biopolymers, protamine, and heparin, and then loaded with anticancer drug doxorubicin. The incorporation of the FDA-approved peptide drug protamine as a wall component rendered the capsules responsive to enzyme stimuli. The stimuli-responsive drug release from these nanocapsules was evaluated, and further modulation of capsule permeability to avoid premature release was demonstrated by crosslinking the wall components. The interaction of the nanocapsules with cancer cells was studied using MCF-7 breast cancer cells. These capsules were readily internalized and disintegrated inside the cells, culminating in the release of the loaded doxorubicin and subsequent cell death as observed by confocal microscopy and MTT Assay. The bioavailability studies performed using BALB/c mice revealed that the encapsulated doxorubicin exhibited enhanced bioavailability compared to free doxorubicin. Our results indicate that this stimuli-responsive system fabricated from clinically used FDA-approved molecules and exhibiting minimal premature release has great potential for drug-delivery applications.

Item Type:	Journal Article
Publication:	JOURNAL OF NANOPARTICLE RESEARCH
Publisher:	SPRINGER
Additional Information:	Copy right for this article belongs to the SPRINGER, VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
Keywords:	Layer by Layer technique; Protamine; Nanocapsules; Doxorubicin; Drug delivery; Nanomedicine
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology Division of Mechanical Sciences > Materials Engineering (formerly Metallurgy)
Date Deposited:	02 Apr 2016 10:41
Last Modified:	02 Apr 2016 10:41
URI:	http://eprints.iisc.ac.in/id/eprint/53427

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