Non-invasive transdermal delivery of chemotherapeutic molecules in vivo using superparamagnetic iron oxide nanoparticles

Abstract

Background The skin is both a target and a potential conduit for the delivery of drugs, but its cornified cell layer resists penetration by most molecules. This study investigated the potential of superparamagnetic iron oxide nanoparticles to facilitate the transdermal delivery of anticancer agents. Results Chemotherapeutic cancer drugs were applied with or without nanoparticles to the skin of hairless mice, and their ability to penetrate the skin was assessed using fluorescence microscopy and tumor growth. Nanoparticles enhanced the penetration of the skin by doxorubicin and 5-fluorouracil as determined by fluorescence microscopy and growth retardation of experimental melanoma in immunocompetent, syngeneic mice. This drug enhancement did not require conjugation or encapsulation of the drugs by the nanoparticles—simple co-administration sufficed. Nanoparticles applied topically to melanomas increased the cytotoxicity and immune cell infiltration induced by co-administered 5-fluorouracil, and also reduced vascularization of the tumors independently of 5-fluorouracil. Conclusion Correctly formulated superparamagnetic iron oxide nanoparticles can facilitate the chemotherapeutic effectiveness of cytotoxic drugs on skin tumors by both increasing their transdermal penetration and ameliorating host–tumor interactions. This enhancement of skin penetration occurs without the need for conjugation or encapsulation of the co-administered drugs, and so will likely be applicable to other drugs, also.

The Emerging Role of Ionic Liquid-Based Approaches for Enhanced Skin Permeation of Bioactive Molecules: A Snapshot of the Past Couple of Years

“… inorganic NCs integrate metal-, metal oxide-, and mesoporous silica-based NPs as the most popular examples, although other nanosystems, such as inorganic polymer-based NCs, carbon-, carbon oxide-, or black phosphorus-based nanomaterials, also fit this category [ 99 , 100 , 101 , 102 ]. Although the majority of inorganic NCs in drug delivery, including DTD, has been addressed to cancer theranostics [ 103 ] they have also been explored for antimicrobial therapies [ 104 ], where silver-based NPs (AgNPs) occupy a prominent role, given the intrinsic antibacterial properties of silver [ 52 , 105 ]. For instance, AgNPs synthesized from silver nitrate in the aqueous extract of a medicinal plant ( Acanthospermum australe ) used in South America to treat cSSTI, were recently reported to have potent wide spectrum antimicrobial activity [ 106 ].…”

Transdermal Delivery of Chemotherapeutics: Strategies, Requirements, and Opportunities

“…Tumor volume monitored over 17 days showed significant reduction of tumor growth in group with SPIONs + 5-FU compared to 5-FU alone and vehicle treated. Further they also demonstrated enhanced permeation of DOX through the dorsal mouse skin with SPIONs compared to DOX alone [126].…”

Magnetic Nanoparticles Used in Oncology

“…In this way, the overall toxicity of the treatment is decreased, and the active substance does not demonstrate chemical or physical degradation. In recent studies, TMZ, doxorubicin, paclitaxel and 5-fluorouracil were combined with SPIONs [101][102][103].…”