The aim of this study was to establish a paclitaxel (PTX)-loaded mixed micelle delivery system (PTX-TP-M) with vitamin E-TPGS (TPGS) and Plasdone®S-630 Copovidone (PVPS630) as carriers to improve the solubility, oral absorption, and anti-tumor activity of PTX against lung cancer. In this study, PTX-TP-M was prepared using the ethanol thin-film dispersion method followed by characterization of the binary mixed micelles system. The average size of the PTX-TP-M was 83.5?±?1.8?nm with a polydispersity index of 0.265?±?0.007 and the drug loading (DL%) and entrapment efficiency (EE%) were 3.09?±?0.09% and 95.67?±?2.84%, respectively, which contributed to a high solubility of PTX about 24947-fold increase in water (4.78?±?0.14?mg/mL). In addition, TEM analysis showed that the PTX-TP-M appeared spherical in structure and was well dispersed without aggregation and adhesion. In vitro release studies showed that the PTX-TP-M displayed a sustained release compared to free PTX in the dialysis bag. The efflux ratio of PTX reduced from 44.83 to 3.52 when formulated as PTX-TP-M; a 92.15% reduction, studied using the Caco-2 monolayer model. The oral bioavailability of PTX also improved by 4.35-fold, suggesting that PTX-TP-M can markedly promote the absorption in the gastrointestinal tract. Using in vitro MTT assays, it was observed that cytotoxicity was markedly increased, and IC50 values of PTX-TP-M (3.14?±?0.85 and 8.28?±?1.02?μg/mL) were lower than those of PTX solution (5.21?±?0.93 and 14.53?±?1.96?μg/mL) in A549 and Lewis cell, respectively. In vivo anti-tumor studies showed that PTX-TP-M achieved higher anti-tumor efficacy compared with PTX in Lewis bared C57BL/6 mice. Furthermore, a gastrointestinal safety assay also proved the safety of PTX-TP-M. All results demonstrated that the PTX-TP-M exhibited great potential for delivering PTX with increased solubility, oral bioavailability, and anti-cancer activity and this binary mixed micelles drug delivery system has potential to be used clinically. 相似文献
Aims: To evaluate the prevalence of hyperglycemia among inpatients in internal medicine, and specifically, to assess the glycemic management of inpatients in non-endocrinology departments in three large urban hospitals in China.
Methods: A multicenter observational study was conducted using electronic health records, and a survey of 1939 patients who were admitted to internal medicine units and followed until discharge. Those with previously diagnosed diabetes, newly diagnosed diabetes, or impaired fasting glucose were included. Aspects of glycemic management examined were (a) hyperglycemia, (b) endocrinology consultation for hyperglycemia and (c) hypoglycemia.
Results: The prevalence of hyperglycemia in internal medicine was 45.7% (886 out of 1939). A total of 741 (83.6%) patients were treated by non-endocrinology departments; of those, 230 (31.1%) were in poor glycemic control and needed an endocrinology consultation. Yet only 57 (24.8%) received one. In 4 cases, the physician did not follow the consultants’ advice. Among the remaining 53 consulted patients, 35 (66.1%) were still in poor glycemic control, yet only about half received a second consultation. Finally, among patients treated in non-endocrinology departments, 58 (7.8%) had hypoglycemia; less than half retested their blood glucose after treatment.
Conclusions: The majority of patients with hyperglycemia were in non-endocrinology departments. Their glycemic management was poor; the endocrinology consultation rate was low and the result was suboptimal. Also, the management of hypoglycemia was not ideal. Therefore, improving glycemic management is urgently needed in Chinese hospitals. 相似文献
1.?Sennoside A (SA) is a newly identified necrosis-avid agent that shows capability for imaging diagnosis and tumor necrosis targeted radiotherapy. As a water-soluble compound, 131I-Sennoside A (131I-SA) might be excreted predominately through the kidneys with the possibility of nephrotoxicity.2.?To further verify excretion pathway and examine nephrotoxicity of 131I-SA, excretion and nephrotoxicity were appraised. The pharmacokinetics, hepatotoxicity and hematotoxicity of 131I-SA were also evaluated to accelerate its possible clinical translation. All these studies were conducted in mice with ethanol-induced muscular necrosis following a single intravenous administration of 131I-SA at 18.5 MBq/kg or 370 MBq/kg.3.?Excretion data revealed that 131I-SA was predominately (73.5% of the injected dose (% ID)) excreted via the kidneys with 69.5% ID detected in urine within 72 h post injection. Biodistribution study indicated that 131I-SA exhibited initial high distribution in the kidneys but subsequently a fast renal clearance, which was further confirmed by the results of autoradiography and single-photon emission computed tomography-computed tomography (SPECT-CT) imaging. The maximum necrotic to normal muscle ratio reached to 7.9-fold at 48?h post injection, which further verified the necrosis avidity of 131I-SA. Pharmacokinetic parameters showed that 131I-SA had fast blood clearance with an elimination half-life of 6.7?h. Various functional indexes were no significant difference (p?>?0.05) between before administration and 1 d, 8 d, 16 d after administration. Histopathology showed no signs of tissue damage.4.?These data suggest 131I-SA is a safe and promising necrosis-avid agent applicable in imaging diagnosis and tumor necrosis targeted radiotherapy. 相似文献