Characterization and Assessment of Nanoencapsulated Sanguinarine Chloride as a Potential Treatment for Melanoma

May 2015 | Volume 14 | Issue 5 | Original Article | 453 | Copyright © 2015

Jamie Rosen BA,a* Angelo Landriscina BA,a* Brandon L. Adler BA,a Aimee Krauz BA,a Jessica Doerner MS,b
Mahantesh Navati PhD,c Tagai Musaev BA,a Claudia Gravekamp PhD,b Joshua Nosanchuk MD,b,d
and Adam J. Friedman MDa,c

aDepartment of Medicine (Division of Dermatology), Albert Einstein College of Medicine, Bronx, NY
bDepartment of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY
cDepartment of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY
dDepartment of Medicine (Infectious Disease), Albert Einstein College of Medicine, Bronx, NY
*Both authors contributed equally to the production of this work.

Abstract

Sanguinarine has a history of use in both folk medicine and early dermatology for the treatment of cutaneous neoplasms. Applied indiscriminately, bloodroot is an escharotic agent with potential to cause extensive tissue necrosis. However, when used in a controlled fashion, sanguinarine imparts selective cytotoxic/anti-proliferative activity through multiple mechanisms against human/ murine melanoma. To exploit sanguinarine’s observed activity against melanoma, a targeted delivery system is required. We present a sol-gel based nanoparticulate platform for encapsulating sanguinarine chloride(sang-np)—a targeted therapeutic capable of steady, reliable delivery of predictable quantities of drug over a sustained time period with minimal undesirable effects. Size and release kinetics of sang-np were characterized using dynamic light scattering and ultraviolet-visible spectroscopy respectively. In vitro efficacy of sang-np was assessed. At both 2 and 24 hours, free sanguinarine killed > 90% of B16 melanoma cells, assessed via MTT assay. At 2 hours, sang-np killed a portion of melanoma cells, increasing to percentages comparable to free sanguinarine by 24 hours. Control(empty) nanoparticles exerted minimal toxicity to melanoma cells at both time points. TUNEL assay revealed that treatment with both sanguinarine and sang-np induces apoptosis in B16 melanoma cells, suggesting that both treatments act via the same mechanism of action. These data confirm controlled release of sanguinarine from sang-np, as well as comparable efficacy and mechanism of action to sanguinarine alone. This suggests that nanoparticle delivery of sanguinarine may be a unique approach to capitalize on this potent agent’s inherent anti-tumor activity and overcome many of the limitations with its current formulation.

J Drugs Dermatol. 2015;14(5):453-458.

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INTRODUCTION

Melanoma is one of the few malignancies rising in incidence over the last 30 years. It has been predicted that melanoma incidence will reach 1 in 50 in 2015, with a projected 137,310 new cases expected.1,2 While survival rates for local disease are relatively high (5 year survival 98%), those with regional and metastatic disease have a much poorer prognosis (5 year survival 62% and 16%, respectively).3 It is projected that 9,940 deaths will occur from melanoma in 2015, accounting for 75% of total skin cancer deaths.2,3 Despite the development of new and innovative techniques to treat melanoma, high mutation rates, drug resistance, and early metastases have rendered our current therapeutic armament inadequate.

There is growing interest in the use of nanoscale platforms for the treatment of melanoma in order to provide targeted, efficacious treatment with a lowered risk of adverse events (AEs). Nanoparticulate drugs are defined by their size (< 100 nm) and corresponding properties. Their small size allows for greater penetration past most biological barriers and an augmented surface area to volume ratio, allowing for maximal reactivity. Prior nanoparticulate studies serve as a proof of principal, highlighting the ability of the nanoparticulate platform to deliver therapeutic quantities of the drug over a sustained period of time with minimal side effects.4,5

Nanomaterials are of great interest in the oncology world as a result of the observed inherent tumor targeting capacity from the enhanced penetration and retention effect arising from tumors’ “leaky” vasculature, allowing for a greater accumulation of drug in solid tumors.6 Efficacy of nanotherapeutics in the setting of malignancy has been demonstrated in several studies. For instance, liposomal doxorubicin was found to have a 100-fold longer circulation half-life and sevenfold lower cardiotoxicity than free doxorubicin.7 Another study found that albumin-bound curcumin nanoparticles showed enhanced and sustained accumulation within melanoma regions compared with curcumin alone.8

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