Nanosuspensions of a new compound, ER-β005, for enhanced oral bioavailability and improved analgesic efficacy

Abstract

Estrogen receptor-β005 (ER-β005) is a novel compound developed by our group; however, its application has been greatly hindered due to its low solubility. A nanosuspension of insoluble drugs is a nanoscale colloidal dispersion that has extremely higher drug-loading compared with other nanomedicines. In this study, nanosuspensions of ER-β005 (Nano-ER-β005) stabilized by a food protein, β-casein (β-CN), were prepared via an antisolvent-precipitation method to improve oral absorption and thus promote therapeutic efficacy. Nano-ER-β005, which has a diameter of 110nm and drug-loading of 50%, was developed. Analyses of fluorescence and circular dichroism (CD) spectra demonstrated a strong interaction between β-CN and drug particles in Nano-ER-β005, indicating that β-CN is a potent nanosuspension stabilizer. The oral bioavailability of Nano-ER-β005 was 1.6-fold greater than that of raw drug particles. Additionally, ER-β005 was confirmed to have a strong therapeutic effect against pain reactions in animal models, and inhibition of this effect was significantly increased with Nano-ER-β005 treatment. In conclusion, by using β-CN as a stabilizer, nanosuspensions of ER-β005 were developed and oral absorption was enhanced. Moreover, ER-β005 is a powerful drug that inhibits pain reactions, and its therapeutic efficacy was markedly increased in the Nano-ER-β005.

Keywords: Analgesic efficacy; Bioavailability; ER-β005 (PubChem CID: 16450315); Estrogen receptor agonist; Interaction; Nanosuspensions; Stabilizer; acetone (PubChem CID: 180); capsaicin (PubChem CID: 1548943); dimethyl sulfoxide (PubChem CID: 679); ethyl acetate (PubChem CID: 8857); isoliquiritigenin (PubChem CID: 638278); morphine (PubChem CID: 5288826); phenylephrine (PubChem CID: 6041); sodium dodecyl sulfate (PubChem CID: 3423265); sulprostone (PubChem CID: 5312153).