title: Layer-by-layer polymer coated gold nanoparticles for topical delivery of imatinib mesylate to treat melanoma.
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 the Turkevich method and were stabilized and functionalized using polyvinylpyrrolidone and polyethylene imine. The functionalized AuNP were then sequentially coated with anionic poly(styrenesulfonate) and cationic polyethylene imine and loaded with IM. The layer-by-layer polymer coated AuNP (LbL-AuNP) showed average particle size and zeta-potential 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/cm(2)) 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 (p < 0.001) decreased B16F10 cell viability compared to free IM. We have shown for the first time that IM can be delivered by topical application using LbL coated gold nanoparticles to treat melanoma.
authors.affiliation: Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani , Hyderabad Campus, Shameerpet, Hyderabad 500078, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Labala
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Mandapalli
authors.forename: Abhinav
authors.initials: A
authors.lastname: Kurumaddali
authors.forename: Venkata Vamsi Krishna
authors.initials: VV
authors.lastname: Venuganti
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001702:Biopharmaceutics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020099:Coated Materials, Biocompatible / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry; D000068877:Imatinib Mesylate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007478:Iontophoresis; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D020349:Surface Plasmon Resonance; D034421:Sus scrofa
chemical_list: D000970:Antineoplastic Agents; D020099:Coated Materials, Biocompatible; D004337:Drug Carriers; D053769:Nanocapsules; D011108:Polymers; D006046:Gold; D000068877:Imatinib Mesylate
keywords: B16F10 cells; gold nanoparticles; imatinib mesylate; iontophoresis; layer-by-layer coating; topical delivery