Polymeric nanoparticle encapsulation of a naturally occurring plant scopoletin and its effects on human melanoma cell A375.
OBJECTIVE
We formulated nano-encapsulation of a naturally occurring coumarin-scopoletin (7-hydroxy-6-methoxy coumarin, HMC, C(10)H(8)O(4)), 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-a-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-a-vis unencapsulated HMC.


CONCLUSIONS
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.
Khuda-Bukhsh
Anisur Rahman
AR
Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani, Kalyani 741235, India. prof_arkb@yahoo.co.in
Bhattacharyya
Soumya Sundar
SS
Paul
Saili
S
Boujedaini
Naoual
N
D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003374:Coumarins; D015536:Down-Regulation; D006801:Humans; D007093:Imidazoles; D019344:Lactic Acid; D008545:Melanoma / Q000473:pathology*; D053758:Nanoparticles; D010316:Particle Size; D011091:Polyesters; D011108:Polymers; D012603:Scopoletin / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000473:pathology*; D015854:Up-Regulation
D003374:Coumarins; D007093:Imidazoles; D011091:Polyesters; D011108:Polymers; C517283:coumarin 7; D019344:Lactic Acid; C033616:poly(lactide); C030123:coumarin; D053148:Caspase 3; D012603:Scopoletin