International Journal of Nanomedicine (Sep 2022)
Preparation of Betulinic Acid Galactosylated Chitosan Nanoparticles and Their Effect on Liver Fibrosis
Abstract
Zi Chao Wu,1,2,* Xin Yu Liu,1,* Jia Yan Liu,1 Jing Shu Piao,1 Ming Guan Piao1,3 1School of Pharmacy, Yanbian University, Yanji, 133002, People’s Republic of China; 2Research Institute, Shijiazhuang Yiling Pharmaceutical Co., Ltd, Shijiazhuang, 050035, People’s Republic of China; 3Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanbian University, Yanji, 133002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ming Guan Piao; Jing Shu Piao, Email [email protected]; [email protected]: Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver.Materials and Methods: Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA-GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro.Results: BA-GC-NPs with diameters < 200 nm were manufactured in a virtually spherical core-shell arrangement, and BA was released consistently and continuously for 96 h, as assessed by an in vitro release assay. According to the safety evaluation, BA-GC-NPs demonstrated good biocompatibility at the cellular level and did not generate any inflammatory reaction in mice. Importantly, BA-GC-NPs showed an inherent liver-targeting potential in the uptake behavioral studies in cells and bioimaging tests in vivo. Efficacy tests revealed that administering BA-GC-NPs in a mouse model of liver fibrosis reduced the degree of liver injury in mice.Conclusion: The findings showed that BA-GC-NPs form a safe and effective anti-hepatic fibrosis medication delivery strategy.Keywords: nanoparticles, lactobionic acid, chitosan, liver fibrosis, betulinic acid
