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1.
Comput Intell Neurosci ; 2021: 7517791, 2021.
Article in English | MEDLINE | ID: mdl-34707652

ABSTRACT

This paper aims to systematically analyze the reasons for the differences in the relationship between transformational leadership (TL) and project success and apply meta-analysis to summarize which dimensions of TL are the main driving forces for project success. Adopting the meta-analysis approach, we investigated 31 independent studies (N = 6475) and studied the theoretical moderators of this relationship from the perspectives of mediating variables, cultural background, and document type to test whether the moderating effects can explain the inconsistent research results. The results reveal that TL positively affects project success and leadership charm is the primary driver of TL. Also, the existence of a mediating mechanism has a more significant impact on the success of the leading project. Meanwhile, compared with project construction under the Western cultural background, countries with Eastern culture are more inclined to use a people-oriented philosophy for project management to promote project success. This research provides an empirical perspective to help project leaders select management talents, regulate leaders' words and deeds, and cultivate technical and soft leadership skills. Besides, this paper proposes a unique and nuanced view of the relationship between TL and project success, enhancing people's understanding of the TL's role in influencing project success.


Subject(s)
Leadership , Humans
2.
Expert Opin Drug Deliv ; 10(5): 559-71, 2013 May.
Article in English | MEDLINE | ID: mdl-23373755

ABSTRACT

OBJECTIVES: This work aimed to evaluate pharmacokinetics, biodistribution, toxicity, and antitumor activities of a highly stable long-/medium-chain triglycerides (LCT/MCT)-based etoposide parenteral emulsion (EPE) in comparison to etoposide parenteral solution (EPS). METHODS: Using high-pressure homogenization method, EPE was prepared and sterilized at 121°C for 10 min by autoclaving. The biological samples were analyzed using the UPLC-ESI-MS/MS method. RESULTS: Superior stability of EPE was verified with no significant changes in physicochemical properties in the accelerating and long-term stability tests. Similar pharmacokinetic behavior in beagle dogs was obtained and the AUC 0 - 12h values were 1196.73 ± 320.85 and 1505.56 ± 617.93 µg.h/L for EPE and EPS (p > 0.5), respectively. Likewise, no remarkable difference in biodistribution profiles in mice was found for both formulations. Safety assessment studies including hemolysis test, rabbit ear vein test and injection anaphylaxis were undertaken and the EPE was proven to be safe for intravenous administration. Specifically, after consecutive 12 weeks administration in rats, systematic and local toxicity induced by EPE were alleviated relative to that of EPS. Furthermore, significant and comparable antitumor activities to EPS were also demonstrated by EPE with tumor suppression rate (TSR) of 66.63, 55.94, and 60.16% against H460, Hep G2, and BCAP-37 human cancer cell lines in nude mice at the dose of 15 mg/kg, respectively. CONCLUSION: These results suggest that this LCT/MCT-based lipid emulsion is a promising alternative intravenous carrier for etoposide with high stability, improved convenience, alleviated toxicity, and noncompromised antitumor efficacy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Drug Carriers , Etoposide/pharmacokinetics , Fat Emulsions, Intravenous/chemistry , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/toxicity , Area Under Curve , Dogs , Etoposide/chemistry , Etoposide/pharmacology , Etoposide/toxicity , Female , Guinea Pigs , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasms, Experimental/drug therapy , Rabbits , Rats , Rats, Sprague-Dawley , Tandem Mass Spectrometry , Tissue Distribution , Triglycerides/chemistry , Tumor Cells, Cultured
3.
Drug Dev Ind Pharm ; 39(9): 1447-56, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23020091

ABSTRACT

The aim of the investigation was to compare the effectiveness of two absorption enhancers, sodium caprate (C10) and sodium deoxycholate (SDC), in increasing the bioavailability of a poorly absorbed paracellar flux drug, berberine chloride, across the intestinal mucosae of rats in vivo, together with examination of their effects on mucosal damage. In addition, all four intestinal segments were collected after administration of the enhancers and sodium saline. The results of the bioavailability experiments showed the oral absorption of berberine chloride was poor and both C10 and SDC could significantly improve the very poor absorption of berberine chloride. After co-administration, the area under the plasma concentration-time curve of berberine chloride was increased 41.1-fold by C10 (100 mg/kg) and 35.3-fold by SDC (100 mg/kg) compared with that in the absence of C10 and SDC, respectively. Local toxicity experiment indicated that both enhancers caused no specific damage to the intact intestine. This study demonstrates that C10 and SDC could significantly promote the absorption of berberine chloride from the gastrointestinal tract with few toxic effects, which might be due mainly to relaxing the absorption limitation while inhibiting the efflux transporter of berberine chloride by the enhancers. Besides, this could lead to the development of new drug-enhancers.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacokinetics , Berberine/pharmacokinetics , Decanoic Acids/chemistry , Deoxycholic Acid/chemistry , Excipients/chemistry , Intestinal Absorption , Intestinal Mucosa/metabolism , Animals , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/blood , Antineoplastic Agents, Phytogenic/chemistry , Berberine/adverse effects , Berberine/blood , Berberine/chemistry , Biological Availability , Decanoic Acids/adverse effects , Deoxycholic Acid/adverse effects , Excipients/adverse effects , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Magnetic Resonance Spectroscopy , Male , Random Allocation , Rats , Rats, Wistar , Spectroscopy, Fourier Transform Infrared , Up-Regulation
4.
Drug Dev Ind Pharm ; 38(1): 104-10, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21774632

ABSTRACT

Berberine chloride (BBR) is a plant alkaloid that has been used for centuries for treatment of inflammation, dysentery, and liver diseases. It is poorly absorbed from the gastrointestinal (GI) tract and its various clinical uses are limited because of its poor bioavailability. The object of the present study was to investigate the absorption enhancing effect of chitosan on BBR. Mixtures of BBR and chitosan were prepared and the absorption enhancement was investigated in rats. The results showed a dose-dependent absorption enhancement produced by chitosan. Formulations containing 0.5%, 1.5%, and 3.0% chitosan resulted in improvement of AUC(0-36 h) values by 1.9, 2.2, 2.5 times. The absorption enhancing ability of chitosan may be due to its ability to improve the BBR paracellular pathway in the intestinal tract. Chitosan hydrochloride, a salt of chitosan, was also investigated in this study. However, the addition of 2.0% and 3.3% chitosan hydrochloride to BBR solution did not produce any increase in either C(max) or AUC(0-36 h) of BBR. Subsequent solubility studies suggested that the reduced berberine chloride solubility in chitosan hydrochloride may limit the enhancement ability. This study showed that the optimum formulation producing the highest BBR absorption is the BBR solution containing 3.0% chitosan.


Subject(s)
Berberine/chemistry , Berberine/pharmacokinetics , Chitosan/chemistry , Intestinal Absorption , Animals , Area Under Curve , Biological Availability , Chemistry, Pharmaceutical/methods , Gastrointestinal Tract/metabolism , Male , Rats , Rats, Wistar , Solubility , Solutions/chemistry
5.
AAPS PharmSciTech ; 12(2): 705-11, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21637946

ABSTRACT

Berberine chloride (BBR) is a natural isoquinoline alkaloid extracted from medicinal herbs. It has been reported that the intestinal absorption of BBR is very low. In this study, the absolute bioavailability of BBR was studied, and the enhancing effects of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on intestinal absorption were investigated in rats. BBR injection was administrated via the femoral vein at a dose of 1.0 mg kg(-1) in intravenous group, and BBR oral formulations were administrated by oral gavage at a dose of 100 mg kg(-1) in BBR control (control) group and BBR-TPGS (test) group, respectively. The result showed that BBR had a very low absolute bioavailability of 0.68%, and TPGS could enhance intestinal absorption of BBR significantly. TPGS at a concentration of 2.5% could improve peak concentration (C(max)) and area under the curve (AUC(0-36)) of BBR by 2.9 and 1.9 times, respectively. The absorption enhancing ability of TPGS may be due to its ability to affect the biological activity of P-glycoprotein and thereby reduce the excretion of absorbed BBR into the intestinal lumen. This study indicated that absolute bioavailability of BBR was 0.68% in rats, and TPGS was a good absorption enhancer capable of enhancing intestinal absorption of BBR significantly.


Subject(s)
Berberine/pharmacokinetics , Drug Carriers/pharmacokinetics , Intestinal Absorption/physiology , Vitamin E/analogs & derivatives , Administration, Oral , Animals , Berberine/administration & dosage , Berberine/standards , Biological Availability , Drug Carriers/administration & dosage , Drug Carriers/standards , Drug Synergism , Intestinal Absorption/drug effects , Male , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/standards , Random Allocation , Rats , Rats, Wistar , Vitamin E/administration & dosage , Vitamin E/pharmacokinetics , Vitamin E/standards
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