RESUMEN
Nanocomposites prepared with a terpolymer of poly(L-lactide) (PLLA)-poly(ε-caprolactone) (PCL)-poly(ethylene glycol) (PEG) and partially oxidized carbon nanotubes (CNTspo) were synthesized and characterized to evaluate their ability to act as an effective nanocarrier of the anticancer drug methotrexate. The homopolymers of PLLA and PCL were synthesized through ring-opening polymerization (ROP) and characterized through gel permeation chromatography (GPC). The PLLA-PCL-PEG terpolymers were synthesized through a four-step chemical route using oxalyl chloride as a linker agent and analyzed with 1H-NMR, 13C-NMR, and FTIR spectroscopies. Additionally, the nanocomposites were characterized through FTIR, and X-ray photoelectron spectroscopy (XPS), as well as the differential scanning calorimetry (DSC) technique. XPS analysis revealed that PLLA-PCL-PEG terpolymer chains are grafted onto CNTspo. Moreover, evaluations through FTIR and DSC strongly suggest that the PCL-rich domains are preferentially oriented toward CNTspo. The release tests exhibited a "burst effect" profile, which was more evident in the terpolymers than in the nanocomposites. Five models were used to assess methotrexate's in vitro release. For the nanocomposites, the best fit to the experimental data was obtained using the first-order model, whereas the results obtained from the Korsmeyer-Peppas model indicated that Fickian diffusion drives methotrexate's release.
RESUMEN
Breast cancer (BC) has surpassed lung cancer as the most diagnosed cancer and, in terms of mortality, is the fifth leading cause with 684,996 new deaths (6.7% of all cancer-related deaths) and the highest mortality amongst all cancers (15.5%) in women. Selective estrogen-receptor modulators (SERMs) have been used for the last thirty years for estrogen receptor-positive (ER+) BC prevention and treatment. Tamoxifen (TAM), the most widely used SERM, is orally administered and its long-term oral administration has been associated to toxicity and adverse side effects. Endoxifen (EDX) is one of the known active metabolites of TAM, with an affinity to ERα 100 times higher than TAM. Furthermore, EDX has shown antiproliferative activity against the ER+ BC cell line MCF-7. Alternative administration routes that avoid the metabolic processing of TAM seem an appealing alternative to its oral administration. With this aim, we have prepared a polymeric gel-like solution of Pluronic® F127 as vehicle for topical administration of EDX. In order to shed light on the potential clinical use of this formulation, we have compared it with the standard pharmaceutical form, i.e. orally administered TAM. The biodistribution, antitumor efficacy and toxic effects of topical EDX and oral TAM were evaluated in ER+ tumor xenograft athymic nu/nu mouse models. The results showed a statistically significant antitumor effect and reduced toxicity of topical EDX as compared to oral TAM or empty F127 gel. This novel administration route of SERMs could also have a strong impact in the prevention of BC at early development stages and could help to ameliorate the mortality and morbidity related to this disease.
Asunto(s)
Neoplasias de la Mama , Moduladores Selectivos de los Receptores de Estrógeno , Humanos , Femenino , Ratones , Animales , Receptores de Estrógenos/metabolismo , Modelos Animales de Enfermedad , Distribución Tisular , Tamoxifeno/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismoRESUMEN
The potential application of biodegradable and biocompatible polymeric micelles formed by Pluronic F127 and P104 as nanocarriers of the antineoplastic drugs docetaxel (DOCE) and doxorubicin (DOXO) is presented in this work. The release profile was carried out under sink conditions at 37 °C and analyzed using the Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin diffusion models. The cell viability of HeLa cells was evaluated using the proliferation cell counting kit CCK-8 assay. The formed polymeric micelles solubilized significant amounts of DOCE and DOXO, and released them in a sustained manner for 48 h, with a release profile composed of an initial rapid release within the first 12 h followed by a much slower phase the end of the experiments. In addition, the release was faster under acidic conditions. The model that best fit the experimental data was the Korsmeyer-Peppas one and denoted a drug release dominated by Fickian diffusion. When HeLa cells were exposed for 48 h to DOXO and DOCE drugs loaded inside P104 and F127 micelles, they showed lower IC50 values than those reported by other researchers using polymeric nanoparticles, dendrimers or liposomes as alternative carriers, indicating that a lower drug concentration is needed to decrease cell viability by 50%.
RESUMEN
Coagulative nucleation in the copolymerization of methyl methacrylate-butyl acrylate (MMA-BA) via semicontinuous emulsion heterophase polymerization (SEHP) under monomer-starved conditions in latexes with high solid content (50.0 wt %) and low concentrations of surfactant is reported. The SEHP technique allows the obtention of latex with high colloidal stability and has potential industrial application in polymer synthesis. High instantaneous conversions (>90%) and a high-ratio polymerization rate/addition rate (Rp/Ra) ≥ 0.9 were obtained at low times until the final copolymerization, which confirmed the starved conditions in the systems at the highest surfactant concentrations. The particle size exhibited a linear size increment at conversions between 0 and 40% induced by homogeneous nucleation, a transition region between 40 and 50%, and non-linear behavior at higher conversions by coagulative nucleation. These three behaviors were also observed in the particle surfactant coverage area (Sc), Z-potential, particle coagulation rate (dNp/dt) by the Smoluchowski model, final particle size (Dpz), and number particle (Np) through the reaction. By means of transmission electron microscopy (TEM) images, the onset of coagulation was observed from 50% of conversion until the end of the reaction. In addition, in both processes of copolymerization, tacticity was displayed (mainly syndiotacticity).
RESUMEN
The use of colloidal particles (CPs) in the transport of drugs is developing rapidly thanks to its effectiveness and biosafety, especially in the treatment of various types of cancer. In this study Rose Bengal/PLGA CPs synthesized by double emulsion (W/O/W) and by electrostatic adsorption (layer-by-layer), were characterized and evaluated as potential breast cancer treatment. CPs were evaluated in terms of size, zeta potential, drug release kinetics and cell viability inhibition efficacy with the triple negative breast cancer cell line HCC70. The results showed that both types of CPs can be an excellent alternative to conventional cancer treatment by taking advantage of the enhanced permeation and retention (EPR) effect, manifested by solid tumors; however, the double emulsion CPs showed more suitable delivery times of up to 60% within two days, while layer-by-layer showed fast release of 50% in 90â¯min. Both types of CPs were capable to decrease cell viability, which encourage us to further testing in in vivo models to prove their efficacy and feasible use in the treatment of triple negative breast cancer.
Asunto(s)
Antineoplásicos/química , Neoplasias de la Mama/tratamiento farmacológico , Portadores de Fármacos/química , Ácido Láctico/química , Ácido Poliglicólico/química , Rosa Bengala/química , Adsorción , Antineoplásicos/uso terapéutico , Transporte Biológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Coloides , Portadores de Fármacos/uso terapéutico , Liberación de Fármacos , Emulsiones , Humanos , Ácido Láctico/síntesis química , Imagen Óptica , Tamaño de la Partícula , Ácido Poliglicólico/síntesis química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Electricidad Estática , Propiedades de SuperficieRESUMEN
In this work, we present a detailed study of the potential application of polymeric micelles and gels of four different reverse triblock poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) copolymers (BOnEOmBOn, where n denotes the respective block lengths), specifically BO8EO90BO8, BO14EO378BO14, BO20EO411BO20 and BO21EO385BO21, as effective drug transport nanocarriers. In particular, we tested the use of this kind of polymeric nanostructures as reservoirs for the sustained delivery of the antifungals griseofulvin and fluconazole for oral and topical administration. Polymeric micelles and gels formed by these copolymers were shown to solubilize important amounts of these two drugs and to have a good stability in physiologically relevant conditions for oral or topical administration. These polymeric micellar nanocarriers were able to release drugs in a sustained manner, being the release rate slower as the copolymer chain hydrophobicity increased. Different sustained drug release profiles were observed depending on the medium conditions. Gel nanocarriers were shown to display longer sustained release rates than micellar formulations, with the existence of a pulsatile-like release mode under certain solution conditions as a result of their inner network structure. Certain bioadhesive properties were observed for the polymeric physical gels, being moderately tuned by the length and hydrophobicity of the polymeric chains. Furthermore, polymeric gels and micelles showed activity against the yeast Candida albicans and the mould demartophytes (Trichophyton rubrum and Microsporum canis) and, thus, may be useful for the treatment of different cutaneous fungal infections.