RESUMO
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.
RESUMO
Hexagonal liquid crystals and supramolecular polymers from meglumine-based supra-amphiphiles were developed as drug delivery systems to be applied on the skin. The influence of fatty acid unsaturation on the structure and mechanical properties was evaluated. Moreover, we have investigated the system biocompatibility and how the type of water could influence its bioadhesive properties. Meglumine-oleic acid (MEG-OA) was arranged as hexagonal liquid crystals at 30-70â¯wt% water content, probably due to its curvature and increased water solubility. Meglumine-stearic acid (MEG-SA) at 10-80â¯wt% water content self-assembled as a lamellar polymeric network, which can be explained by the low mobility of MEG-SA in water due to hydrophobic interactions between fatty acid chains and H-bonds between meglumine and water molecules. Both systems have shown suitable mechanical parameters and biocompatibility, making them potential candidates to encapsulate therapeutic molecules for skin delivery. Moreover, a strong positive correlation between the amount of unfrozen bound water in meglumine-based systems and the bioadhesion properties was observed. This work shows that a better understanding of the physicochemical properties of a drug delivery system is extremely important for the correlation with the desired biological response and, thus, improve the product performance for biomedical applications.
Assuntos
Sistemas de Liberação de Medicamentos , Meglumina/química , Pele/química , Tensoativos/química , Água/química , Adesão Celular , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Meglumina/síntese química , Meglumina/farmacologia , Tamanho da Partícula , Relação Estrutura-Atividade , Propriedades de Superfície , Tensoativos/síntese química , Tensoativos/farmacologia , ViscosidadeRESUMO
We developed a magnetic solid lipid nanoparticles formulation of paclitaxel (PTX-loaded MSLNs) via emulsification-diffusion method. The physicochemical characterization of PTX-loaded MSLNs was performed by AFM, DLS, determination of entrapment efficiency (EE) and drug loading (DL), DSC, VSM, and physical stability. The in vitro effect of temperature and pulsed magnetic hyperthermia on drug release were studied. PTX-loaded MSLNs had a particle diameter around 250â¯nm with a narrow size distribution, spherical morphology, EE of 67.3⯱â¯1.2% and a DL of 17.1⯱â¯0.4⯵g/mg. A decrease of the melting point of the lipid was observed following the preparation of the MSLNs. A threefold increase in the in vitro drug release rate was seen when temperature was raised from 25 to 43⯰C. The lipid coating of MPs confer a temperature-dependent drug release and magnetic hyperthermia was used to trigger controlled PTX release from MSLNs.