Bioavailability and pharmacokinetics of bufadienolides‐loaded lipid microspheres after different administrations to rats

Abstract

The degradation kinetics in vitro and pharmacokinetics of bufadienolides loaded in lipid microsphere (BU-LM) after intravenous (IV) administration were investigated and compared with bufadienolides solution (BU-S). The bioavailabilities of BU-LM after intraportal (F IP ), intraduodenal (F ID ), and intragastric (F IG ) administrations to rats were also evaluated. The degradation kinetics showed that BU-LM could protect bufadienolides from rapid metabolism in the plasma and gastrointestinal tract. The pharmacokinetic study revealed that BU-LM after IV administration exhibited longer half-life, longer mean residence time and higher apparent volume of distribution than intravenous BU-S. After different routes of administration of BU-LM, cinobufagin (C), and resibufogenin (R) were metabolized completely and could not be detected at an oral dose of 6 mg/kg. Furthermore, C exhibited a complete hepatic first-pass effect after IP administration of 0.5 mg/kg BU-LM. Bufalin (B), the lowest component of the BU-LM could be detected at any administration and the F IG , F ID , and F IP for B were 43.05, 88.93, and 93.31%, respectively. R had a F ID and F IP of only 1.51 and 2.77%, respectively. The results demonstrated that the stomach appeared to be the dominating site of metabolism for B and the liver for C and R.Practical applications: Bufadienolides, consisting of bufalin (B), binobufagin (C), and resibufogenin (R) are easily hydrolyzed (catalyzed by acids, bases, and enzymes) and are metabolized rapidly in rats because of their chemical structures, especially C. However, the three bufadienolides could be protected from degradation effectively and the degradation half-lives could be extended to different degrees by using lipid microspheres (LM) as a delivery system. Also, after intravenous administration to rats, bufadienolidesloaded lipid microspheres (BU-LM) could slow down the metabolism and elimination of bufadienolides, delay the release and increase the targeted effect of the drug compared with bufadienolides aqueous solution (BU-S iv ). Consequently, LM is a promising alternative vehicle for bufadienolides.

Bufalin-loaded mPEG-PLGA-PLL-cRGD nanoparticles: Preparation, cellular uptake, tissue distribution, and anticancer activity

“…20 The lipid microsphere also exhibited a longer half-life time. 21 The results of nanostructured lipid particles were similar and showed that the chemical stability of bufalin was enhanced by being encapsulated in lipid particles. 22 The merits of these NPs were based on the sustained-release of the drug from the NPs.…”

Buccal Bullfrog (Rana catesbeiana Shaw) Oil Emulsion: A Mucoadhesive System Intended for Treatment of Oral Candidiasis

“…Additionally, the BBE was able to reduce the hemolytic effect of the bullfrog oil from 40 ± 6% to 22 ± 2% at 1.0 mg·mL −1 , highlighting the ability of this system to increase the biocompatibility of the bullfrog oil at this concentration. Indeed, emulsified systems are widely used due to their ability to reduce toxic effects of drugs or natural oils, by promoting a slower release of the active compounds from their internal phase, avoiding an excessive amount of the delivered compound being released at once to promote toxicity or side effects [64,65]. Similar results were reported in the literature in which a submicron emulsion containing bufadienolides was able to reduce the toxicity of this compound [64].…”

Separation and determination of resibufogenin and cinobufagin in Chansu using reversed‐phase liquid chromatography with γ‐cyclodextrin as mobile‐phase modifier

“…Several methods, such as thin layer chromatography , microemulsion electrokinetic chromatography , cyclodextrin‐modified micellar electrokinetic chromatography , liquid chromatography‐mass spectrometry (LC‐MS) , and gas chromatography‐mass spectrometry (GC‐MS) have been developed for separating and determining cinobufagin and resibufogenin in the Chansu. As a simple and widely used method, liquid chromatography (LC) has also been used to separate and determine cinobufagin and resibufogenin, and has been as the quantitative method of cinobufagin and resibufogenin of Chansu in the Chinese Pharmacopoeia (2010 edition). But, the separation for resibufogenin and cinobufagin by LC is difficult on the reversed phase as these molecules are similar, and the separation or the peak shapes of them are poor on the some C 18 column.…”