Proliposomes for oral delivery of total biflavonoids extract from Selaginella doederleinii: formulation development, optimization, and in vitro–in vivo characterization

Abstract

Bing Chen,*,1–3 Xuewen Wang,*,2,3 Dan Lin,2,3 Dafen Xu,2,3 Shaoguang Li,2,3 Jianyong Huang,4 Shaohuang Weng,2,3 Zhen Lin,2,3 Yanjie Zheng,2,3 Hong Yao,2,3 Xinhua Lin2,31Nano Medical Technology Research Institute, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 2Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 3Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4Department of Pharmaceutical, Fujian Medical University Union Hospital, Fuzhou, Fujian, People’s Republic of ChinaCorrespondence: Xinhua Lin; Hong YaoDepartment of Pharmaceutical Analysis, Fujian Medical University, No.1 Xueyuan Road, University Town, Fuzhou 350122, People’s Republic of ChinaEmail [email protected]; [email protected]*These authors contributed equally to this workPurpose: Amentoflavone, robustaflavone, 2’’,3’’-dihydro-3’,3’’’-biapigenin, 3’,3’’’-binaringenin and delicaflavone are five major active ingredients in the total biflavonoids extract from Selaginella doederleinii (TBESD) with favorable anticancer properties. However, the natural-derived potent antitumor agent of TBESD is undesirable due to its poor solubility. The present study was to develop and optimize a proliposomal formulation of TBESD (P-TBESD) to improve its solubility, oral bioavailability and efficacy.Materials and methods: P-TBESD containing a bile salt, a protective hydrophilic isomalto-oligosaccharides (IMOs) coating, were successfully prepared by thin film dispersion-sonication method. The physicochemical and pharmacokinetic properties of P-TBESD were characterized, and the antitumor effect was evaluated using the HT-29 xenograft-bearing mice models in rats.Results: Compared with TBESD, the relative bioavailability of amentoflavone, robustaflavone, 2’’,3’’-dihydro-3’,3’’’-biapigenin, 3’,3’’’-binaringenin and delicaflavone from P-TBESD were 669%, 523%, 761%, 955% and 191%, respectively. The results of pharmacodynamics demonstrated that both TBESD and P-TBESD groups afforded antitumor effect without systemic toxicity, and the antitumor effect of P-TBESD was significantly superior to that of raw TBESD, based on the tumor growth inhibition and histopathological examination.Conclusion: Hence, IMOs-modified proliposomes have promising potential for TBESD solving the problem of its poor solubility and oral bioavailability, which can serve as a practical oral preparation for TBESD in the future cancer therapy.Keywords: Selaginella doederleinii, proliposomes, sodium deoxycholate, oral bioavailability, antitumor

Keywords

• Selaginella doederleinii
• Proliposomes
• Sodium deoxycholate
• Oral bioavailability
• Antitumor