RESUMEN
PURPOSE: To develop a novel docetaxel (DOC)-loaded lipid microbubbles (MBs) for achieving target therapy and overcoming the poor water-solubility drawback of DOC. METHODS: A novel DOC-loaded microbubble (DOC + MB) was prepared by lyophilization and the physicochemical properties including ultrasound contrast imaging of the liver were measured. The anti-tumor effect of the DOC + MBs combined with low-frequency ultrasound (LFUS; 0.8 Hz, 2.56 W/cm², 50% cycle duty) on the DLD-1 cancer cell line was examined using an MTT assay. RESULTS: The physicochemical properties of the two tested formats of DOC + MBs (1.0 mg and 1.6 mg) was shown: concentration, (6.74 ± 0.02) × 108 bubbles/mL and (8.27 ± 0.15) × 108 bubbles/mL; mean size, 3.296 ± 0.004 µm and 3.387 ± 0.005 µm; pH value, 6.67 ± 0.11 and 6.56 ± 0.05; release rate, 3.41% and 12.50%; Zeta potential, -37.95 ± 7.84 mV and -44.35 ± 8.70 mV; and encapsulation efficiency, 54.9 ± 6.21% and 46.3 ± 5.69%, respectively. Compared with SonoVue, the DOC + MBs similarly enhanced the echo signal of the liver imaging. The anti-tumor effect of the DOC + MBs/LFUS group was significantly better than that of DOC alone and that of the normal MBs/LFUS groups. CONCLUSIONS: The self-made DOC + MBs have potential as a new ultrasound contrast agent and drug-loaded microbubble, and can obviously enhance the antitumor effect of DOC under LFUS exposure.
Asunto(s)
Antineoplásicos/química , Sistemas de Liberación de Medicamentos/métodos , Microburbujas/uso terapéutico , Taxoides/química , Taxoides/uso terapéutico , Ultrasonido/métodos , Animales , Antineoplásicos/administración & dosificación , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Docetaxel , Perros , Estabilidad de Medicamentos , Humanos , Concentración de Iones de Hidrógeno , Lípidos/administración & dosificación , Lípidos/química , Hígado/diagnóstico por imagen , Hígado/efectos de los fármacos , Solubilidad , Ultrasonografía , Agua/químicaRESUMEN
AIM: Ghrelin can act as a signal for meal initiation and play a role in the regulation of gastrointestinal (GI) motility via hypothalamic circuit. This study investigated the correlation between changes of hypothalamic ghrelin system and GI motility dysfunction and anorexia in rats with chronic renal failure (CRF). METHODS: Sprague-Dawley (SD) rats (male/female 1:1, 180 ± 20 g) were randomly classified into a CRF group and control group (n = 8 per group). 5/6 nephrectomy was used to construct the CRF model. When plasma creatinine concentration (PCr) and blood urea nitrogen (BUN) in the CRF group were twice higher than the normal, food intake (g/24 h) and gastrointestinal interdigestive myoelectric complex (IMC) were detected. Then all rats were killed for assessment of the mRNA expression of ghrelin and growth hormone secretagogue receptor (GHS-R) in hypothalamus using reverse transcription-polymerase chain reaction. Analysis of variance, Student-Newman-Keuls-q-test and Correlation Analysis were used to do statistical analysis. P < 0.05 was considered as statistically significant. RESULTS: Compared to the control group, the CRF group was obviously decreased in the food intake (g/24 h), the phase III duration and amplitude and the ghrelin and GHS-R expression in the hypothalamus (P < 0.05). There was a positive correlation between them (P < 0.05). CONCLUSION: Changes of ghrelin and GHS-R in the hypothalamus correlate with gastrointestinal motility dysfunction and anorexia in rats with CRF.
Asunto(s)
Anorexia/etiología , Enfermedades Gastrointestinales/etiología , Motilidad Gastrointestinal , Ghrelina/metabolismo , Hipotálamo/metabolismo , Fallo Renal Crónico/complicaciones , Uremia/etiología , Animales , Anorexia/genética , Anorexia/metabolismo , Anorexia/fisiopatología , Biomarcadores/sangre , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Modelos Animales de Enfermedad , Ingestión de Alimentos , Femenino , Enfermedades Gastrointestinales/genética , Enfermedades Gastrointestinales/metabolismo , Enfermedades Gastrointestinales/fisiopatología , Ghrelina/genética , Hipotálamo/fisiopatología , Fallo Renal Crónico/genética , Fallo Renal Crónico/metabolismo , Fallo Renal Crónico/fisiopatología , Masculino , Complejo Mioeléctrico Migratorio , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores de Ghrelina/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Uremia/genética , Uremia/metabolismo , Uremia/fisiopatologíaRESUMEN
BACKGROUND/AIMS: Ghrelin plays a central role in the regulation of gastrointestinal (GI) motility. This study aimed to investigate the expression of ghrelin and growth hormone secretagogue receptor (GHSR) in the central nervous system of rats with chronic renal failure (CRF). METHODS: Sprague-Dawley rats (male, 180 ± 20 g, n = 24) were treated by 5/6 nephrectomy to construct CRF model. As their plasma creatinine concentration and blood urea nitrogen were maintained more than double the normal level for 2 weeks, they were killed for assessing the expression of ghrelin and GHSR in hypothalamus and hippocampus using immunohistochemistry and real-time polymerase chain reaction (RT-PCR). The rats (male, 180 ± 20 g, n = 24) treated by Sham operation served as a control. One-way analysis of variance and Student-Newman-Keuls q test were used to analyze group difference and a p-value of <0.05 was considered as statistically significant. RESULTS: Compared with the controls, the ghrelin and GHSR expression was obviously increased in the hippocampus (p < 0.05) but decreased in the hypothalamus of rats with CRF (p < 0.05). CONCLUSIONS: CRF was found to impact the expression of ghrelin and GHSR in hypothalamus and hippocampus. This might be associated with the CRF-induced GI motility dysfunction.