RESUMEN
Background: Serious side effects caused by paclitaxel formulation, containing toxic solubilizer Cremophor® EL, and its nonspecific accumulation greatly limit clinical paclitaxel application. Aim: To design paclitaxel-loaded copolymer of lactic and glycolic acids nanoparticles decorated with alpha-fetoprotein third domain (rAFP3d-NP) to increase paclitaxel safety profile. Methods: rAFP3d-NP was obtained via carbodiimide technique. Results: The particles were characterized with high paclitaxel loading content of 5% and size of 280 nm. rAFP3d-NP revealed biphasic profile with 67% release of paclitaxel during 220 h. Increased area under the curveinf and mean residence time values after rAFP3d-NP administration confirmed prolonged blood circulation compared with paclitaxel. rAFP3d-NP demonstrated significant tumor growth inhibition at 4T1 and SKOV-3 models. Conclusion: rAFP3d-NP is a promising delivery system for paclitaxel and can be applied similarly for delivery of other hydrophobic drugs.
Asunto(s)
Nanopartículas , Neoplasias , Humanos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , alfa-Fetoproteínas , Nanopartículas/química , Paclitaxel/química , Polímeros/química , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Portadores de Fármacos/químicaRESUMEN
Co-encapsulation of abiraterone acetate (AbrA) and docetaxel (Dtx) in polymeric nanoparticles as novel prototypes for prostate cancer treatment combining hormonal and chemotherapy was designed. Nanoparticles (NPs) composed of poly(dl-lactide-co-glycolide) (PLGA) were prepared by single-emulsion solvent evaporation technique and characterized in terms of morphology with atomic force microscopy and transmission electron microscopy. HPLC method for simultaneous determination of AbrA and Dtx encapsulation efficacy was developed. Also differential scanning calorimetry and Fourier-transform infrared spectroscopy were provided. To study the effectiveness of cellular internalization and distribution of NPs with AbrA and Dtx co-encapsulation (NP-AbrA/Dtx), a fluorescence microscopy was utilized. NPs prepared had size 256.3 ±9.4 nm and zeta potential -18.4 ±1.4 mV. Encapsulation efficacy for AbrA was 68.7% and for Dtx was 74.3%. NPs were able to control the AbrA and Dtx release within 24 h. The mathematical model of drug release was performed. The results obtained from confocal microscopy showed the effective accumulation of the NP-AbrA/Dtx in the cytoplasm of cells. Synthesized NPs possessed satisfactory parameters and a biphasic release profile, proceeding by the Fick diffusion mechanism, which provide prolonged release of the drugs and maintenance of their concentration. It was shown that NPs loaded with AbrA and Dtx exhibited a high cytotoxic activity on the LNCaP cell line, similar to the combination of free drugs of AbrA and Dtx, but in contrast to the combination of substances, had a synergistic mechanism of action. Our findings support the potential use of developed NPs in further in vivo studies. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1150-1158, 2019.
Asunto(s)
Androstenos , Docetaxel , Portadores de Fármacos , Nanopartículas , Neoplasias , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Células A549 , Androstenos/química , Androstenos/farmacocinética , Androstenos/farmacología , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Docetaxel/química , Docetaxel/farmacocinética , Docetaxel/farmacología , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Humanos , Nanopartículas/química , Nanopartículas/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Neoplasias/patología , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacocinética , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacologíaRESUMEN
PURPOSE: The aim of this study was to compare the physico-chemical and biological properties of polymeric nanoparticles obtained from poly(DL-lactide-co-glycolide) (PLGA) with different ratios of monomers loaded with daunorubicin (DNR). METHODS: DNR-loaded nanoparticles (NPs) were prepared with use of modified simultaneous double-emulsion solvent evaporation/diffusion technique. NPs were characterized using dynamic light scattering, atomic force microscopy, transmission electron microscopy, scanning electron microscopy, and differential scanning calorimetry and Fourier transform infrared spectroscopy. RESULTS: NPs with DNR were differing in size and zeta potential, depending on the type of polymer. The data obtained show that total content of DNR correlates with the values of the binding constant of DNR with polymers. The release of DNR from NPs proceeds predominantly for polymers with lower binding constants. The in vitro study of NPs on the MCF-7 cells showed similar activity of particles and substances while for the anthracycline-resistant MCF-7Adr cells the cytotoxicity of the nanoparticles was 3 to 7 times higher depending on the type of copolymer. CONCLUSIONS: PLGA DNR-loaded nanoparticles can be used to overcome multidrug resistance (MDR) as well as for reducing the frequency of DNR reception due to the prolonged effect, which allows maintaining the concentration of the drug at the required level. The usefulness of binding constant calculations for obtaining nanoparticles with the maximum drug loading was proven. The rate of drug administration and the frequency of administration can be calculated based on the DNR release profiles and release parameters that depend on polymer type.