Enhanced antitumor efficacy of folate targeted nanoparticles co-loaded with docetaxel and curcumin.

BACKGROUND: The current study aimed to investigate whether the novel folate (FT) modified nanoparticles (NPs) co-loaded with docetaxel (DT) and curcumin (CU) (named as FT-NPs) could enhance the delivery efficiency to tumor compared with the NPs without FT (non-targeted NPs). METHODS: FT-NPs were successfully formulated in this article. In vitro cytotoxic activity against A549 cells and in vivo antitumor activity of FT-NPs in S180 cell bearing mice were conducted. Cellular uptake test was used to evaluate uptake efficiency of FT-NPs. Histological observation was used to determine the lung security. Besides, the physical chemical properties such as stability, particle size, zeta potential, drug encapsulation efficiency, transmission electron microscopy (TEM) were also conducted. RESULTS: FT-NPs exhibited stronger growth inhibition effects on A549 cells compared with non-targeted NPs, moreover, the novel FT-NPs indicated more effective antitumor efficacy in inhibiting tumor growth. Confocal laser scanning microscopy indicated that the uptake of FT-NPs was facilitated and effective. Histological observation meant that FT-NPs were biocompatible and appropriate for pulmonary administration. CONCLUSION: These results confirmed that FT-NPs with relatively high drug loading capacity could effectively inhibit tumor growth and reduce toxicity. The novel FT-NPs could produce as an outstanding nanocarrier for the targeted treatment of cancers.

Investigation of inclusion complex of cilnidipine with hydroxypropyl-ß-cyclodextrin.

The objective of this study was to improve the water-solubility and photostability of cilnidipine by complexing it with hydroxypropyl-ß-cyclodextrin (HP-ß-CD or HP-beta-CD). The interactions of cilnidipine and HP-ß-CD were characterized by ultra violet-visible (UV/VIS) spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transformation-infrared (FT-IR) spectroscopy and (1)H nuclear magnetic resonance ((1)H NMR) spectroscopy to verify the formation of cilnidipine-HP-ß-CD complex inclusion. Moreover, the binding sites in the HP-ß-CD structure were also tracked through (1)H NMR spectroscopy analysis. All the characterization information proved the formation of cilnidipine-HP-ß-CD inclusion complex, and the results demonstrated the superiority of the inclusion complex in dissolution rates and photostability; in addition, the apparent solubility of cilnidipine was increased more than 10,000-fold in the presence of HP-ß-CD. The stability constant (1:1) was found to be 50,116 M(-1), suggesting a high tendency of the drug to enter the HP-ß-CD cavity. These results identified the cilnidipine-HP-ß-CD inclusion complex as an effective new approach to design a novel formulation for pharmaceutical application.

[Experimental study of pharmaceutic stress myocardial perfusion imaging with higenamine].

OBJECTIVE: To evaluate the applicative value of higenamine used as a new agent for pharmaceutical stress test in detection of coronary artery disease by radionuclide myocardial perfusion imaging. METHODS: Thirteen pigs with chronic coronary artery stenosis by placement of the Ameroid constrictor in the middle section of left anterior descending artery were included in this study. Rest, higenamine and dobutamine stress radionuclide myocardial perfusion imaging was performed with Tc-99m-sestamibi. RESULTS: The sensitivity for detection of coronary artery disease by radionuclide myocardial perfusion imaging was 85% in both higenamine and dobutamine stress imaging. Imaging scores (9.9 +/- 8.5 vs. 9.4 +/- 8.6, P = NS) and defect severity (68% +/- 12% vs. 68% +/- 15%, P = NS) showed no significant difference between higenamine and dobutamine stress test. Agreement of imaging scores between higenamine and dobutamine stress imaging was good (kappa = 0.849, P < 0.0001). CONCLUSION: Our study demonstrates that detection of coronary artery stenosis and ischemic myocardium by myocardial perfusion imaging with higenamine is highly sensitive.

[Pharmacokinetics and relative bioavailability of probucol inclusion complex capsule in healthy dogs].

AIM: To study the pharmacokinetics and relative bioavailability of probucol inclusion complex capsule. METHODS: Following oral administration of a single dose of 250 mg of conventional tablet (formulation A, purchased from the market) and probucol inclusion complex capsule (formulation B, a new formulation for preclinical trial) to each of 6 healthy dogs in a randomized crossover design, the plasma levels of the active drug at different time points were determined by HPLC and the plasma concentration-time profiles of formulation A and B were obtained. The pharmacokinetic parameters as well as relative bioavailability were analyzed. RESULTS: The concentration-time curves of formulation A and formulation B were found to fit a two-compartment open model. The Tmax values of formulation A and formulation B were (9.3 +/- 2.1) h and (9.3 +/- 2.1) h, the Cmax values were (1.5 +/- 1.0) microgram.mL-1 and (2.3 +/- 0.9) microgram.mL-1 and the AUC0-240 values were (85 +/- 56) microgram.h.mL-1 and (134 +/- 55) microgram.h.mL-1, respectively. The relative bioavailability of formulation B was found to be (198 +/- 90)% compared with formulation A. The results of variance analysis and two one-side t-test showed that there was significant difference between the two formulations in the AUC0-240. CONCLUSION: The high bioavailability by the inclusion of formulation B is attributed to the improvement of its water-solubility by the inclusion process and this is supposed to be a key factor for improving drug bioavailability.