Development and In Vivo Evaluation of Ziyuglycoside I–Loaded Self-Microemulsifying Formulation for Activity of Increasing Leukocyte

Abstract

Ziyuglycoside I (ZgI), a major effective ingredient of Sanguisorba officinalis L, has shown good activity in increasing leukocyte of myelosuppression mice. However, oral ZgI therapy has been deterred by poor bioavailability because of its low aqueous solubility and permeability. Our study was to develop ZgI-loaded self-microemulsifying drug delivery system (SMEDDS) and evaluate its intestinal absorption, and pharmacokinetic and pharmacodynamic activity for increasing leukocyte. The formulation was designed and optimized by measuring the equilibrium solubility of ZgI in different vehicles and the pseudoternary phase diagram. Further, morphology, particle size, stability, in vitro release, in situ single-pass intestinal perfusion (SPIP), in vivo activity, and in vivo pharmacokinetic (PK) of ZgI-SMEDDS were charactered or studied. Optimized formulations for in vitro dissolution were Obleique CC497, Tween-20, and Transcutol HP with a proportion of 0.25/0.45/0.30 via D-optimal mixture design. Results showed that the solubility of ZgI was enhanced up to 23.93 mg/g and its average particle size was 207.92 ± 2.13 nm. The release of ZgI had been greatly improved by the SMEDDS. In SPIP, the intestinal absorption of SMEDDS was much better than plain ZgI. In PK, we found the oral bioavailability of ZgI-SMEDDS was 6.94-fold higher absolute bioavailability (21.94 ± 4.67) % than ZgI (3.16 ± 0.89) %. The most important was that the mice WBC of ZgI-SMEDDS group was significantly higher than that of the ZgI group. Our study suggested that SMEDDS could increase the solubility of ZgI, which was beneficial to improve oral bioavailability and enhance biological activity.

<p>Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma</p>

“…First, the composition of the initial formulation was obtained by screening high ILQ solubility surfactants, cosurfactants and oil phase excipients. 41,42 The solubility of ILQ at 25°C in various solvents is shown in Table 1. Amongst the oils screened, castor oil (CO, 28.80 ± 1.28 mg/g) and ethyl oleate (EO, 10.03 ± 0.75 mg/g) showed much better solubility than oleic acid (2.03 ± 0.56 mg/g).…”

Application of Design of Experiments in the Development of Self-Microemulsifying Drug Delivery Systems

“… Response surface plot in three-dimension (3D) (left) and the contour plot (right) for the mixture design of the ( a ) globule size and ( b ) cumulative drug release in pH 1.2 media from the study of clofazimine in solid SMEDDS by Dhaval and coworkers. Adapted from Dhaval and coworkers [ 94 ]. …”

A Comprehensive Review of Genus Sanguisorba: Traditional Uses, Chemical Constituents and Medical Applications

“…Ziyuglycoside I, which is one of the main active ingredients in the Sanguisorba officinalis white tablet, is clinically proven to reduce leukopenia. Since ZY-I exhibits low solubility and permeability when administered orally, a ZY-I-loaded self-microemulsifying drug delivery system has been developed to improve the bioavailability and intestinal absorption of ZY-I, thereby increasing the pharmacokinetics and pharmacodynamic activity of leukocyte ( Xiong et al, 2019 ). In addition, through searching Cochrane Library database ( Cochrane Library, 2021 ), records in the four trials, there prescription containing composition S. officinalis treatment of ulcerative colitis ( Table 2 ).…”