Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma

Relton R Oliveira; Emílio R Cintra; Ailton A Sousa-Junior; Larissa C Moreira; Artur C G da Silva; Ana Luiza R de Souza; Marize C Valadares; Marcus S Carrião; Andris F Bakuzis; Eliana M Lima

doi:10.3390/pharmaceutics15030818

Paclitaxel-Loaded Lipid-Coated Magnetic Nanoparticles for Dual Chemo-Magnetic Hyperthermia Therapy of Melanoma

Pharmaceutics. 2023 Mar 2;15(3):818. doi: 10.3390/pharmaceutics15030818.

Affiliations

¹ FarmaTec-Laboratory of Pharmaceutical Technology, School of Pharmacy, Federal University of Goiás, Alameda Flamboyant, Qd. K, Ed. LIFE, Parque Tecnológico Samambaia, Goiânia 74690-631, Brazil.
² ToxIn-Laboratory of Education and Research in In Vitro Toxicology, Federal University of Goiás, Alameda Flamboyant, Qd. K, Ed. LIFE, Parque Tecnológico Samambaia, Goiânia 74690-631, Brazil.
³ Physics Institute, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia, Goiânia 74690-900, Brazil.
⁴ CNanoMed-Nanomedicine Integrated Research Center, Federal University of Goiás, Alameda Flamboyant, Qd. K, Ed. LIFE, Parque Tecnológico Samambaia, Goiânia 74690-631, Brazil.

Abstract

Melanoma is the most aggressive and metastasis-prone form of skin cancer. Conventional therapies include chemotherapeutic agents, either as small molecules or carried by FDA-approved nanostructures. However, systemic toxicity and side effects still remain as major drawbacks. With the advancement of nanomedicine, new delivery strategies emerge at a regular pace, aiming to overcome these challenges. Stimulus-responsive drug delivery systems might considerably reduce systemic toxicity and side-effects by limiting drug release to the affected area. Herein, we report the development of paclitaxel-loaded lipid-coated manganese ferrite magnetic nanoparticles (PTX-LMNP) as magnetosomes synthetic analogs, envisaging the combined chemo-magnetic hyperthermia treatment of melanoma. PTX-LMNP physicochemical properties were verified, including their shape, size, crystallinity, FTIR spectrum, magnetization profile, and temperature profile under magnetic hyperthermia (MHT). Their diffusion in porcine ear skin (a model for human skin) was investigated after intradermal administration via fluorescence microscopy. Cumulative PTX release kinetics under different temperatures, either preceded or not by MHT, were assessed. Intrinsic cytotoxicity against B16F10 cells was determined via neutral red uptake assay after 48 h of incubation (long-term assay), as well as B16F10 cells viability after 1 h of incubation (short-term assay), followed by MHT. PTX-LMNP-mediated MHT triggers PTX release, allowing its thermal-modulated local delivery to diseased sites, within short timeframes. Moreover, half-maximal PTX inhibitory concentration (IC₅₀) could be significantly reduced relatively to free PTX (142,500×) and Taxol^® (340×). Therefore, the dual chemo-MHT therapy mediated by intratumorally injected PTX-LMNP stands out as a promising alternative to efficiently deliver PTX to melanoma cells, consequently reducing systemic side effects commonly associated with conventional chemotherapies.

Keywords: B16F10 cells; magnetic hyperthermia; magnetosomes; paclitaxel; triggered release.

Grants and funding

This research was partially funded by the Brazilian agencies CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), including INCT NanoFarma (Institutos Nacionais de Ciência e Tecnologia de Nanotecnologia Farmacêutica) and CAPES (Coordenação para Aperfeiçoamento de Pessoal de Nível Superior).