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
Affiliations
Relton R. Oliveira
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
Emílio R. Cintra
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
Ailton A. Sousa-Junior
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
Larissa C. Moreira
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
Artur C. G. da Silva
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
Ana Luiza R. de Souza
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
Marize C. Valadares
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
Marcus S. Carrião
Physics Institute, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia, Goiânia 74690-900, Brazil
Andris F. Bakuzis
Physics Institute, Federal University of Goiás, Avenida Esperança, s/n, Campus Samambaia, Goiânia 74690-900, Brazil
Eliana M. Lima
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
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.
