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Polymeric nanoparticle encapsulation of a naturally occurring plant scopoletin and its effects on human melanoma cell A375

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Author(s): Anisur Rahman Khuda-Bukhsh

Journal: Zhong Xi Yi Jie He Xue Bao
ISSN 1672-1977

Volume: 8;
Issue: 9;
Start page: 853;
Date: 2010;
Original page

Keywords: polylactic-co-glycolic acid | nanoparticles | scopoletin | melanoma | apoptosis | antineoplastic agents | phytogenic | in vitro

ABSTRACT
Objective: We formulated nano-encapsulation of a naturally occurring coumarin — scopoletin (7-hydroxy-6-methoxy coumarin, HMC, C10H8O4), isolated from plant Gelsemium sempervirens having anticancer potentials, with a bio-adhesive agent — polylactic-co-glycolic acid (PLGA) and tested if its cellular uptake, bioavailability and apoptotic (anticancer) potentials could thus be increased vis--vis unencapsulated HMC.Methods: A375 melanoma cancer cells were used for testing cellular entry and anticancer potentials of HMC and nano-7-hydroxy-6-methoxy coumarin (NHMC) through several standard protocols. Characterization of NHMC was done by dynamic light scattering for determination of particle size, polydispersity index (PDI), and zeta potential. Surface morphology of nanoparticles was determined by scanning electron microscopy and atomic force microscopy.Results: HMC was encapsulated with more than 85% entrapment efficiency, the average particle size of NHMC being less than 110 nm and a PDI 0.237, which resulted in enhanced cellular entry and greater bioavailability. NHMC showed a faster cellular uptake (15 min) than its unencapsulated counterpart (30 min). Study of signal molecules through mRNA expressions revealed that NHMC caused down-regulation of cyclin-D1, proliferating cell nuclear antigen (PCNA), survivin and Stat-3, and up-regulation of p53 and caspase-3, that in turn induced a greater number of apoptosis vis--vis unencapsulated HMC.Conclusion: The formulation yielded small-sized NHMC by biodegradable PLGA that took less time for cellular entry, and caused more apoptosis to cancer cells, but apparently had negligible cytotoxicity against normal skin cells. Nano-encapsulation of bioactive plant ingredients can be a strategy worth trying for designing effective chemopreventive drug products.
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