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.
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Acknowledgments
The authors would like to extend their gratitude to the Advanced Facility for Microscopy and Microanalysis, for providing the electron microscopy facility; the Department of Microbiology and Cell Biology, for the confocal microscopy facility; and the Central Animal facilities in the Indian Institute of Science for providing us with animals for in vivo studies.
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Krishna Radhakrishnan, Midhun B. Thomas and Sreeranjini Pulakkat have contributed equally to this work.
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Radhakrishnan, K., Thomas, M.B., Pulakkat, S. et al. Stimuli-responsive protamine-based biodegradable nanocapsules for enhanced bioavailability and intracellular delivery of anticancer agents. J Nanopart Res 17, 341 (2015). https://doi.org/10.1007/s11051-015-3145-8
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DOI: https://doi.org/10.1007/s11051-015-3145-8