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Layer-by-layer polymer coated gold nanoparticles for topical delivery of imatinib mesylate to treat melanoma Suman Labala, Praveen Kumar Mandapalli, Abhinav Kurumaddali, and Venkata Vamsi Krishna Venuganti Mol. Pharmaceutics, Just Accepted Manuscript • DOI: 10.1021/mp5007163 • Publication Date (Web): 14 Jan 2015 Downloaded from http://pubs.acs.org on January 15, 2015
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Molecular Pharmaceutics
Layer-by-layer polymer coated gold nanoparticles for topical delivery of imatinib mesylate to treat melanoma Suman Labala, Praveen Kumar Mandapalli, Abhinav Kurumaddali, Venkata Vamsi Krishna Venuganti* Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, India.
* Corresponding author: Address: Department of Pharmacy, BITS Pilani, Hyderabad Campus, Shameerpet, Hyderabad 500078, Telangana, India. Phone: +91-040-66303581 Fax: +91-040-66303998 Email:
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Molecular Pharmaceutics
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Molecular Pharmaceutics
ABSTRACT The aim of this study was to investigate the feasibility of using layer-by-layer polymer coated gold nanoparticles (AuNP) as a carrier for topical iontophoretic delivery of imatinib mesylate (IM). AuNP were prepared by Turkevich method and were stabilized and functionalized using polyvinyl pyrrolidone and polyethylene imine. The functionalized AuNP were then sequentially coated with anionic poly(styrene sulfonate) and cationic polyethylene imine and loaded with IM. The layer-by-layer polymer coated AuNP (LbL-AuNP) showed average particle size and zetapotential of 98.5 ± 4.3 nm and 32.3 ± 1.3 mV respectively. After LbL coating of AuNP, the surface plasmon resonance wavelength shifted from 518 to 530 nm. The loading efficiency of IM in LbL-AuNP was found to be 28.3 ± 2.3% which was greatest for any small molecule loaded in AuNP. In vitro skin penetration studies in excised porcine ear skin showed that iontophoresis (0.47 mA/cm2) application enhanced the skin penetration of IM loaded AuNP by 6.2-fold compared to passive application. Tape stripping studies showed that iontophoresis of IM loaded LbL-AuNP retained 7.8 and 4.9-fold greater IM in stratum corneum and viable skin respectively compared with iontophoresis of free IM. LbL-AuNP were taken up rapidly (15 min) by B16F10 murine melanoma cells. Furthermore IM loaded LbL-AuNP significantly (p100 nm. On the other hand, micelles and metal-based nanoparticles can be prepared with particle size
