RESUMEN
Ehrlich tumors were grown in female balb mice by subcutaneous injection of Ehrlich ascites carcinoma cells. Mice bearing Ehrlich tumor were injected with saline, DOX in solution or DOX encapsulated within liposomes prepared from DMPC/CHOL/DPPG/PEG-PE (100:100:60:4) in molar ratio. Cytotoxicity assay showed that the IC50 of liposomes containing DOX was greater than that DOX only. Tumor growth inhibition curves in terms of mean tumor size (cm(3)) were presented. All the DOX formulations were effective in preventing tumor growth compared to saline. Treatment with DOX loaded liposomes displayed a pronounced inhibition in tumor growth than treatment with DOX only. Histopathological examination of the entire tumor sections for the various groups revealed marked differences in cellular features accompanied by varying degrees in necrosis percentage ranging from 12% for saline treated mice to 70% for DOX loaded liposome treated mice. The proposed liposomal formulation can efficiently deliver the drug into the tumor cells by endocytosis (or passive diffusion) and lead to a high concentration of DOX in the tumor cells. The study showed that the formulation of liposomal doxorubicin improved the therapeutic index of DOX and had increased anti-tumor activity against Ehrlich tumor models.
RESUMEN
Tailoring nanomaterials with tunable properties is of great importance to develop multifunctional candidates in the biomedical field. In the present study, we aimed to develop a promising nano-hybrid system composed of chitosan (CS) and mesoporous silica nanoparticles with a silver nanoshell coat (CS-AgMSNs). The physicochemical properties of CS-AgMSNs films were characterized using various techniques. Further, the mechanical properties of CS-AgMSNs were evaluated and compared with those of undoped CS film. Moreover, the antimicrobial activities of CS-AgMSNs (with different concentrations) were assessed against E-coli, S. aureus, C. albicans, and A. niger. Our results demonstrated that increasing the concentrations of doped AgMSNs (10 to 40 mg) in CS films lowered their transparency and blocked light transmission effectively. The measured elastic modulus of CS-AgMSNs films (20 and 30 mg) showed a decrease in the stiffness of CS films. Also, the elongation at break for CS-AgMSNs (40 mg) indicated a better flexibility. CS-AgMSNs films (10-40 mg) showed an enhanced antimicrobial activity in a concentration-dependent manner compared to undoped CS films. Collectively, the results suggest that our nano-hybrid CS-AgMSNs matrix has unique and promising properties, and holds potential for use in the biomedical field, food packaging, and textile industry.
Asunto(s)
Antiinfecciosos/farmacología , Fenómenos Químicos , Quitosano/farmacología , Nanocáscaras/química , Plata/química , Bacterias/efectos de los fármacos , Módulo de Elasticidad , Pruebas de Sensibilidad Microbiana , Nanocáscaras/ultraestructura , Fenómenos Ópticos , Porosidad , Espectrometría por Rayos X , Espectroscopía Infrarroja por Transformada de Fourier , Resistencia a la Tracción , Difracción de Rayos X , Levaduras/efectos de los fármacosRESUMEN
Natural protein-based nanoparticles are promising nano-vehicles for the delivery of chemotherapeutic drugs. Caseinate nanoparticles loaded with doxorubicin (CasNPs-DOX) have been surface-modified with the natural polysaccharide alginate to generate the novel nanocarrier Alg-CasNPs-DOX. The fabricated nanoparticles have been characterised by transmission electron microscopy, Fourier-transform infrared spectroscopy, dynamic light scattering, fluorescence spectroscopy, and zeta potential measurement. Drug encapsulation and release profiles were also investigated. In vivo studies were conducted to evaluate the therapeutic efficacy of this novel drug delivery system in tumour-bearing mice. The biodistribution and toxicity of the nano-formulation were also assessed. The results showed that encapsulation of DOX in Alg-CasNPs-DOX not only led to controlled and sustained drug release but also significantly enhanced the effectiveness of DOX against Ehrlich carcinoma. Moreover, no significant changes were observed in liver and kidney enzymes, indicating the selective delivery of DOX to the tumour site, thus minimising DOX toxicity to certain vital organs. Accordingly, Alg-CasNPs-DOX was shown as a promising DOX nanocarrier for improving the therapeutic efficacy of DOX against cancer compared to that of free DOX.
Asunto(s)
Alginatos/química , Caseínas/química , Doxorrubicina/química , Portadores de Fármacos/química , Nanopartículas/química , Liberación de Fármacos , Agua/químicaRESUMEN
AIM: In this study, in vivo biodistribution, clearness and toxicity of curcumin capped iron oxide nanoparticles (Cur-IONPs) were addressed in different body organs. MATERIALS AND METHODS: The physicochemical properties of the prepared Cur-IONPs were investigated. Long term (3â¯weeks) biodistribution, clearness and toxicity were assessed for a single-dose administration of Cur-IONPs (5â¯mg/kg). The iron content in liver, kidney, spleen and brain was quantified using atomic absorption spectroscopy. Serum biochemical parameters were also measured. KEY FINDINGS: The integrated in vivo results demonstrated that Cur-IONPs was mostly taken up in the liver and spleen reaching its highest levels on days 1 and 2, respectively. In the brain, the results showed significant accumulation of Cur-IONPs between 1â¯h to 1-day post injection. This represented the successful penetration Cur-IONPs across the blood-brain barrier. Serum biochemical analysis demonstrated a temporal disturbance in the performance of body organs. Also, the body weights showed no alteration throughout the experiment. SIGNIFICANCE: It has been deduced that the promising green synthesized Cur-IONPs as an "All in One" nanoplatform is safe enough to be used in diagnostic and therapeutic purposes.
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Curcumina/metabolismo , Curcumina/farmacología , Nanopartículas del Metal/administración & dosificación , Animales , Encéfalo/efectos de los fármacos , Curcumina/toxicidad , Compuestos Férricos/metabolismo , Compuestos Férricos/farmacología , Hierro/metabolismo , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Masculino , Nanopartículas del Metal/uso terapéutico , Ratones , Ratones Endogámicos BALB C , Bazo/efectos de los fármacos , Distribución TisularRESUMEN
Treatment of approximately 50% of human cancers includes the use of chemotherapy. The major problem associated with chemotherapy is the inability to deliver pharmaceuticals to specific site of the body without inducing normal tissue toxicity. Latterly, magnetic targeted drug delivery (MTD) has been used to improve the therapeutic performance of the chemotherapeutic agents and reduce the severe side effects associated with the conventional chemotherapy for malignant tumors. In this study, we were focused on designing biocompatible magnetic nanoparticles that can be used as a nanocarrier's candidate for MTD regimen. Magnetic gold nanoparticles (MGNPs) were prepared and functionalized with thiol-terminated polyethylene glycol (PEG), then loaded with anti-cancer drug doxorubicin (DOX). The physical properties of the prepared NPs were characterized using different techniques. Transmission electron microscopy (TEM) revealed the spherical mono-dispersed nature of the prepared MGNPs with size about 22 nm. Energy dispersive X-ray spectroscopy (EDX) assured the existence of both iron and gold elements in the prepared nanoparticles. Fourier transform infrared (FTIR) spectroscopy assessment revealed that PEG and DOX molecules were successfully loaded on the MGNPs surfaces, and the amine group of DOX is the active attachment site to MGNPs. In vivo studies proved that magnetic targeted drug delivery can provide a higher accumulation of drug throughout tumor compared with that delivered by passive targeting. This clearly appeared in tumor growth inhibition assessment, biodistribution of DOX in different body organs in addition to the histopathological examinations of treated and untreated Ehrlich carcinoma. To assess the in vivo toxic effect of the prepared formulations, several biochemical parameters such as aspartate aminotransferase (AST), alanine transaminase (ALT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), urea, uric acid and creatinine were measured. MTD technology not only minimizes the random distribution of the chemotherapeutic agents, but also reduces their side effects to healthy tissues, which are the two primary concerns in conventional cancer therapies.
Asunto(s)
Antineoplásicos/química , Doxorrubicina/química , Oro/química , Nanopartículas de Magnetita/química , Nanopartículas del Metal/química , Animales , Antineoplásicos/farmacología , Células Cultivadas , Doxorrubicina/farmacología , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos/métodos , Femenino , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos BALB C , Polietilenglicoles/química , Espectrometría por Rayos X/métodos , Distribución TisularRESUMEN
Magnetic targeted drug delivery (MTD), using magnetic gold nanoparticles (Fe3O4@Au NPs) conjugated with an anti-cancer drug is a promise modality for cancer treatment. In this study, Fe3O4@Au NPs were prepared and functionalized with thiol-terminated polyethylene glycol (PEG), then loaded with anti-cancer drug doxorubicin (DOX). The physical properties of the prepared NPs were characterized using different techniques. Transmission electron microscopy (TEM) revealed the mono dispersed nature of Fe3O4@Au NPs with an average size of 20 nm which was confirmed using Dynamic light scattering (DLS) measurements. Zeta potential measurements along with UV-VIS spectroscopy demonstrated surface DOX loading on Fe3O4@Au NPs. Energy Dispersive X-ray Spectroscopy (EDX) assured the existence of both iron and gold elements in the prepared NPs. The paramagnetic properties of the prepared NPs were assessed by vibrating sample magnetometer (VSM). The maximum DOX-loading capacity was 100 µg DOX/mg of Fe3O4@Au NPs. It was found that DOX released more readily at acidic pH. In vitro studies on MCF-7 cell line elucidated that DOX loaded Fe3O4@Au NPs (Fe3O4@Au-PEG-DOX) have more potent therapeutic effect than free DOX. Knowledge gained in this study may open the door to pursue Fe3O4@Au NPs as a viable nanocarriers for different molecules delivery in many diagnostic and therapeutic applications.