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Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation.

Cai S, Shi CH, Zhang X, Tang X, Suo H, Yang L, Zhao Y - Int J Nanomedicine (2014)

Bottom Line: The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension.Improved solubility and lymphatic transport may contribute to this enhanced bioavailability.Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, The First Affiliated Hospital of China Medical University, People's Republic of China.

ABSTRACT
The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3β;12β;20-triol (25-OCH3-PPD). Optimized SMEDDS formulations for 25-OCH3-PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH3-PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH3-PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route.

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Chemical structure of 20(S)-25-OCH3-PPD.
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f1-ijn-9-913: Chemical structure of 20(S)-25-OCH3-PPD.

Mentions: 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a novel dammarane-type triterpene sapogenin (Figure 1), was isolated from total hydrolyzed saponins extracted from the leaves of Panax notoginseng using conventional and reverse-phase silica gel chromatography by Zhao et al.1 In a wide variety of cancer cells, it demonstrated the strongest cytotoxic effects among any of the known ginsenosides tested for tumor cells, particularly for lung cancer cells and prostatic cancer cells.2,3 25-OCH3-PPD decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines.2 It also decreased levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cyclin-dependent kinases 2 and 4) and increased or activated proapoptotic proteins (cleaved poly ADP ribose polymerase, caspase-3, caspase-8, and caspase-9).2 However, 25-OCH3-PPD had extremely low aqueous solubility, indicating low oral bioavailability. Low aqueous solubility is a common characteristic in biophar-maceuticals today, and according to some estimates, over 40% of new chemical entities show poor solubility, which is an obstacle to the use of new compounds.4–6


Self-microemulsifying drug-delivery system for improved oral bioavailability of 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol: preparation and evaluation.

Cai S, Shi CH, Zhang X, Tang X, Suo H, Yang L, Zhao Y - Int J Nanomedicine (2014)

Chemical structure of 20(S)-25-OCH3-PPD.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3928458&req=5

f1-ijn-9-913: Chemical structure of 20(S)-25-OCH3-PPD.
Mentions: 20(S)-25-methoxyl-dammarane-3β, 12β, 20-triol (25-OCH3-PPD), a novel dammarane-type triterpene sapogenin (Figure 1), was isolated from total hydrolyzed saponins extracted from the leaves of Panax notoginseng using conventional and reverse-phase silica gel chromatography by Zhao et al.1 In a wide variety of cancer cells, it demonstrated the strongest cytotoxic effects among any of the known ginsenosides tested for tumor cells, particularly for lung cancer cells and prostatic cancer cells.2,3 25-OCH3-PPD decreased survival, inhibited proliferation, induced apoptosis, and led to G1 cell cycle arrest in both cell lines.2 It also decreased levels of proteins associated with cell proliferation (MDM2, E2F1, cyclin D1, and cyclin-dependent kinases 2 and 4) and increased or activated proapoptotic proteins (cleaved poly ADP ribose polymerase, caspase-3, caspase-8, and caspase-9).2 However, 25-OCH3-PPD had extremely low aqueous solubility, indicating low oral bioavailability. Low aqueous solubility is a common characteristic in biophar-maceuticals today, and according to some estimates, over 40% of new chemical entities show poor solubility, which is an obstacle to the use of new compounds.4–6

Bottom Line: The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension.Improved solubility and lymphatic transport may contribute to this enhanced bioavailability.Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy, The First Affiliated Hospital of China Medical University, People's Republic of China.

ABSTRACT
The objective of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) to enhance the oral bioavailability of the poorly water-soluble compound 20(S)-25-methoxydammarane-3β;12β;20-triol (25-OCH3-PPD). Optimized SMEDDS formulations for 25-OCH3-PPD contained Cremophor® EL (50%) as the surfactant, glycerin (20%) as the cosurfactant, and Labrafil® M1944 (30%) as the oil. The SMEDDS were characterized by morphological observation and mean droplet size. The pharmacokinetics and bioavailability of the 25-OCH3-PPD suspension and SMEDDS were evaluated and compared in rats. The plasma concentrations of 25-OCH3-PPD and its main metabolite, 25-OH-PPD, were determined by ultra performance liquid chromatography-tandem mass spectrometry. The relative bioavailability of SMEDDS was dramatically enhanced by an average of 9.8-fold compared with the suspension. Improved solubility and lymphatic transport may contribute to this enhanced bioavailability. Our studies highlight the promise of SMEDDS for the delivery of 25-OCH3-PPD via the oral route.

Show MeSH