Ergosterol-loaded poly(lactide-co-glycolide) nanoparticles with enhanced in vitro antitumor activity and oral bioavailability.

Abstract

AIM:

Ergosterol is a plant sterol with anti-tumor and anti-angiogenic activities, but is poorly soluble. In this study, we attempted to enhance its anti-tumor action and oral bioavailability via poly(lactide-co-glycolide) (PLGA) nanoparticle encapsulation.

METHODS:

Ergosterol-loaded PLGA nanoparticles (NPs/Erg) were prepared using the emulsion/solvent evaporation technique. Their physicochemical properties were characterized, and their cytotoxicity against human cancer cell lines was evaluated with MTT assay. The pharmacokinetics and tissue distribution of NPs/Erg were investigated in rats and mice, respectively.

RESULTS:

NPs/Erg were spherical in shape with a particle size of 156.9±4.8 nm and a Zeta potential of -19.27±1.13 mV, and had acceptable encapsulation efficiency and loading capacity. NPs/Erg exerted much stronger cytotoxicity against human cancer cells than the free ergosterol, and showed significantly reduced IC50 values (14.69±0.48 μg/mL in glioma U251 cells; 9.43±0.52 μg/mL in breast cancer MCF-7 cells; 4.70±0.41 μg/mL in hepatoma HepG2 cells). After oral administration of a single dose in rats, NPs/Erg displayed a prolonged plasma circulation with a 4.9-fold increase of oral bioavailability compared with the free ergosterol. After mice received NPs/Erg, the ergosterol in NPs/Erg was rapidly distributed in stomach, kidneys, liver, brain, spleen, and virtually non-existent in heart and lungs. The presence of NPs/Erg in brain was particularly improved compared with the free ergosterol.

CONCLUSION:

The PLGA nanoparticles serve as a promising carrier for the poorly soluble ergosterol and significantly improve its bioavailability, biodistribution and in vitro anti-tumor activities.

• Authors: Hui-Yun Zhang, Caleb Kesse Firempong, Yuan-Wen Wang, Wen-Qian Xu, Miao-Miao Wang, Xia Cao, Yuan Zhu, Shan-Shan Tong, Jiang-Nan Yu, Xi-Ming Xu
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 37 Issue 6 Pg. 834-44 (Jun 2016) ISSN: 1745-7254 [Electronic] United States
• PMID: 27133301 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Polyglactin 910
• Ergosterol

Topics

• Administration, Oral
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology)
• Biological Availability
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Carriers (chemistry)
• Ergosterol (administration & dosage, pharmacokinetics, pharmacology)
• Humans
• Male
• Mice
• Nanoparticles (chemistry)
• Neoplasms (drug therapy, metabolism, pathology)
• Polyglactin 910 (chemistry)
• Rats, Sprague-Dawley