RESUMEN
A multi-component paclitaxel (PTX) -loaded ß-elemene nanoemulsion by transferrin modification (Tf-PE-MEs) was developed to enhance non-small-cell lung cancer (NSCLC) treatment. After transferrin modification, the particle size of Tf-PE-MEs was (14.87 ± 1.84) nm, and the zeta potential was (-10.19 ± 0.870) mV, respectively. In vitro experiments showed that Tf-PE-MEs induced massive apoptosis in A549 cells, indicating that it had significant cytotoxicity to A549 cells. Through transferrin modification, Tf-PE-MEs accumulated at the tumor site efficiently with overexpressed transferrin receptor (TfR) on the surface of A549 cells. This will allow increasing PTX and ß-elemene concentration in the target cells, enhancing the therapeutic effect. Compared to PTX alone, Tf-PE-MEs displayed good anti-tumor efficacy and diminished systemic toxicity in vivo studies. With favourable therapeutic potential, this study provides a new strategy for the combined anticancer treatment of non-small cell lung cancer.
Asunto(s)
Antineoplásicos Fitogénicos , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas , Emulsiones , Neoplasias Pulmonares , Nanopartículas , Paclitaxel , Sesquiterpenos , Transferrina , Paclitaxel/administración & dosificación , Paclitaxel/farmacología , Paclitaxel/química , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Humanos , Transferrina/química , Transferrina/administración & dosificación , Neoplasias Pulmonares/tratamiento farmacológico , Animales , Células A549 , Sesquiterpenos/farmacología , Sesquiterpenos/química , Sesquiterpenos/administración & dosificación , Apoptosis/efectos de los fármacos , Nanopartículas/química , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/química , Ratones Endogámicos BALB C , Ratones Desnudos , Receptores de Transferrina/metabolismo , Tamaño de la Partícula , Ratones , Línea Celular Tumoral , Masculino , Liberación de Fármacos , Supervivencia Celular/efectos de los fármacosRESUMEN
Background: A sequential release co-delivery system is an effective strategy to improve anti-cancer efficacy. Herein, multicomponent-based liposomes (TET-CTM/L) loaded with tetrandrine (TET) and celastrol (CEL)-loaded coix seed oil microemulsion (CTM) were fabricated, which showed synergistic anti-liver cancer activities. By virtue of Enhanced Permeability and Retention (EPR) effect, TET-CTM/L can achieve efficient accumulation at the tumor site. TET was released initially to repair abnormal vessels and decrease the fibroblasts, and CTM was released subsequently for eradication of tumor tissue. Methods: TEM (transmission electron microscopy) and DLS (dynamic light scattering) were adopted to characterize the TET-CTM/L. Flow cytometry was adopted to examine the cellular uptake and cytotoxicity of HepG2 cells. The HepG2 xenograft nude mice were adopted to evaluate the anti-tumor efficacy and systemic safety of TET-CTM/L. Results: TEM images of TET-CTM/L showed the structure of small particle size of CTM within large-size liposomes, indicating that CTM can be encapsulated in liposomes by film dispersion method. In in vitro studies, TET-CTM/L induced massive apoptosis toward HepG2 cells, indicating synergistic cytotoxicity against HepG2 cells. In in vivo studies, TET-CTM/L displayed diminished systemic toxicity compared to celastrol or TET used alone. TET-CTM/L showed the excellent potential for tumor-targeting ability in a biodistribution study. Conclusion: Our study provides a new strategy for combining anti-cancer therapy that has good potential not only in the treatment of liver cancer but also can be applied to the treatment of other solid tumors.
Asunto(s)
Bencilisoquinolinas , Coix , Neoplasias Hepáticas , Triterpenos Pentacíclicos , Animales , Ratones , Humanos , Liposomas , Coix/química , Ratones Desnudos , Distribución Tisular , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Aceites de Plantas/químicaRESUMEN
In this paper, Fe3O4/chitosan/isoniazid magnetic nanoparticles (Fe3O4/CS/INH-MNPs) were prepared as an environmental stimuli-responsive drug-delivery system by automated in situ click technology, in which Fe3O4 magnetic nanoparticles, chitosan and isoniazid were simultaneously in situ crystallized by one-step method. The Fe3O4 magnetic nanoparticles and tripolyphosphate act as stable crosslinkers to produce numerous intermolecular crosslinkages for the mobility of the chitosan chains. Characterization results indicated that the multifunctional drug delivery system with optimized size, excellent loading capacity, well magnetic properties, nontoxicity and pH triggered drug release property is expected to be applied in tuberculosis treatment with excellent magnetic sensitivity and sustained release.
Asunto(s)
Nanopartículas del Metal , Quitosano , Sistemas de Liberación de Medicamentos , Compuestos Férricos , Humanos , Isoniazida , TuberculosisRESUMEN
A novel biocompatible magnetic nanocomposite drug carrier was developed by first chemically modifying a hyperbranched polyester (HBPE) with dodecenyl succinic anhydride (DDSA) functional groups to produce HBPE-DDSA. The magnetic nanocomposite Fe3O4/HBPE-DDSA was then synthesized by dispersing superparamagnetic iron oxide (Fe3O4) nanoparticles within HBPE-DDSA. The structure and magnetic properties of the nanocomposite were characterized by 1H NMR, MALDI-MS, XRD, FTIR, TEM, and SQUID analyses. Isoniazid (INH) was selected as a model antituberculosis drug to investigate the in vitro drug release properties of Fe3O4/HBPE-DDSA/INH. The cytotoxicity of the magnetic nanocomposites was assessed by CCK-8 assay. The results indicated that Fe3O4/HBPE-DDSA is a promising potential drug carrier for a magnetic-targeted drug delivery system.
Asunto(s)
Materiales Biocompatibles/química , Portadores de Fármacos/química , Liberación de Fármacos , Nanopartículas de Magnetita/química , Poliésteres/química , Materiales Biocompatibles/farmacología , Línea Celular , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/farmacología , Isoniazida/química , Nanocompuestos/química , Anhídridos Succínicos/químicaRESUMEN
Our previous studies showed that after oral administration of an Huang-Lian-Jie-Du-Tang (HLJDT) decoction, there is a higher concentration of the pure components, berberine, baicalin and gardenoside in the plasma of Middle cerebral artery occlusion (MCAO) rats than in sham-operated rats, The aim of the present study was to determine whether these components could be reliably measured in MCAO rat tissues. First, the plasma concentration-time profiles of berberine, palmatine, baicalin, baicalein and gardenoside were characterised in MCAO rats after oral administration of the aqueous extract of HLJDT. Subsequently, liver, lung and kidney tissues were obtained from sudden death MCAO rats in the absorption phase (0.25 h), the distribution phase (1.0 h) and the elimination phase (8.0 h) after administration of the HLJDT aqueous extract. An HPLC method was developed and validated for the determination of the distribution characteristics of berberine, palmatine, baicalin, baicalein and gardenoside simultaneously from the above-mentioned rat tissues. The results indicated that berberine, palmatine, baicalin and baicalein distributed rapidly and accumulated at high levels in the lung, while gardenoside distributed widely in the lung and the kidney. To the best of our knowledge, this is the first report to describe the distribution of the active ingredients derived from HLJDT in MCAO rat tissues. The tissue distribution results provide a biopharmaceutical basis for the design of the clinic application of HLJDT in cerebrovascular disease.
Asunto(s)
Medicamentos Herbarios Chinos/farmacocinética , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Animales , Berberina/farmacocinética , Berberina/uso terapéutico , Alcaloides de Berberina/farmacocinética , Alcaloides de Berberina/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Flavanonas/farmacocinética , Flavanonas/uso terapéutico , Flavonoides/farmacocinética , Flavonoides/uso terapéutico , Iridoides/farmacocinética , Iridoides/uso terapéutico , Masculino , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du-Tang (HLJDT, or Oren-gedoku-to in Japanese), an important multi-herb remedy in China and other Asia countries, has been used clinically to treat cerebral ischemia for decades. MATERIALS AND METHODS: According to the previous studies we have reported, an HPLC method was developed and validated for determination of berberine, palmatine, baicalin, baicalein and geniposide simultaneously in MCAO rat plasma after administration of HLJDT aqueous extract. A classified integral pharmacokinetic method was put forward after having compared the integrated concentration-time profile with that of single component. An AUC based weighting approach was used for integrated principle. RESULTS: The results indicated the classified integral pharmacokinetic profile of index components from HLJDT could reveal the pharmacokinetic behavior of original components, and was corresponding to the holistic pharmacological effects of anti-ischemia with HLJDT. CONCLUSIONS: This study was aimed to explore an approach that could be applied to integrate the pharmacokinetic behavior of different components derived from HLJDT. The integrated pharmacokinetic results also provided more information for further understanding of the clinical cerebrovascular disease in use of HLJDT.