Mechanochemical Preparation of Chrysomycin A Self-micelle Solid Dispersion with Improved Solubility and Enhanced Oral Bioavailability

Overview

Journal J Nanobiotechnology

Publisher Biomed Central

Specialty Biotechnology

Date 2021 Jun 1

PMID 34059070

Citations 10

Authors

Zhuomin Xu

Shanshan Zheng

Xin Gao

Yulu Hong

Yue Cai

Qiuqin Zhang

Jiani Xiang

Dehui Xie

Fuxing Song

Huawei Zhang

Hong Wang

Xuanrong Sun

Affiliations

Soon will be listed here.

Abstract

Background: Chrysomycin A (CA) has been reported as numerous excellent biological activities, such as antineoplastic and antibacterial. Though, poor solubility of CA limited its application in medical field. Due to good amphiphilicity and potential anticancer effect of disodium glycyrrhizin (NaGA) as an excipient, an amorphous solid dispersion (NaGA/CA-BM) consisting of CA and NaGA was prepared in the present study by mechanochemical technology (roll mill ML-007, zirconium balls, 30 rpm, 2.5 h) to improve the solubility and oral bioavailability of CA. Then, NaGA/CA-BM was self-assembled to micelles in water. The interaction of CA and NaGA in solid state were investigated by X-ray diffraction studies, polarized light microscopy, and scanning electron microscope. Meanwhile, the properties of the sample solution were analyzed by dynamic light scattering and transmission electron. Furthermore, the oral bioavailability and antitumor ability of NaGA/CA-BM in vivo were tested, providing a theoretical basis for future application of CA on cancer therapy.

Results: CA encapsulated by NaGA was self-assembled to nano-micelles in water. The average diameter of nano-micelle was 131.6 nm, and zeta potential was - 11.7 mV. Three physicochemical detections showed that CA was transformed from crystal into amorphous form after treated with ball milling and the solubility increased by 50 times. Na2GA/CA-BM showed a significant increase of the bioavailability about two time that of free CA. Compared with free CA, the in-vivo antitumor studies also exhibited that NaGA/CA-BM had an excellent inhibition of tumor growth.

Conclusions: NaGA/CA-BM nanoparticles (131.6 nm, - 11.7 mV) prepared by simple and low-cost mechanochemical technology can improve oral bioavailability and antitumor efficacy of CA in vivo, suggesting a potential formulation for efficient anticancer treatment.

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