1. Self-Nanoemulsifying Drug Delivery System of Genkwanin: A Novel Approach for Anti-Colitis-Associated Colorectal Cancer
- Author
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Ting Ouyang, Wei-Guo Chen, Hua-Feng Yin, Shu-Ding Sun, Chun-Ming Yin, Xin Hua He, Xiao-Lin Yang, and Chun-Feng Zhang
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Male ,0301 basic medicine ,Administration, Oral ,Pharmaceutical Science ,Apoptosis ,Pharmacology ,Rats, Sprague-Dawley ,Mice ,chemistry.chemical_compound ,Drug Delivery Systems ,0302 clinical medicine ,Oral administration ,Drug Discovery ,Solubility ,Original Research ,Molecular Structure ,Chemistry ,Colitis ,030220 oncology & carcinogenesis ,Genkwanin ,Drug delivery ,Emulsions ,nanoparticle-based drug delivery system ,Colorectal Neoplasms ,pharmacokinetics ,Drug Compounding ,Structure-Activity Relationship ,03 medical and health sciences ,Pharmacokinetics ,medicine ,Animals ,Humans ,Cell Proliferation ,Drug Design, Development and Therapy ,Intestinal permeability ,Dose-Response Relationship, Drug ,intestinal permeability ,Neoplasms, Experimental ,Flavones ,anticancer efficacy ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Rats ,Bioavailability ,Mice, Inbred C57BL ,030104 developmental biology ,Permeability (electromagnetism) ,Nanoparticles ,Daphne ,insoluble herbal drug - Abstract
Hua-Feng Yin,1,2 Chun-Ming Yin,3 Ting Ouyang,4 Shu-Ding Sun,1 Wei-Guo Chen,1 Xiao-Lin Yang,5 Xin He,6 Chun-Feng Zhang1 1School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, People’s Republic of China; 2Jiangxi QingFeng Pharmaceutical Co., Ltd, Ganzhou, 341000, Jiangxi, People’s Republic of China; 3Emergency Department, The First Affiliated Hospital of Gannan Medical University, Ganzhou, 341000, Jiangxi, People’s Republic of China; 4School of Chinese Materia Medical, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 5Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 6School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Xin HeSchool of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, People’s Republic of ChinaTel +852-54445989Email xhe06@qub.ac.ukChun-Feng ZhangSchool of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of ChinaTel +86-25-86185129Email zhangchunfeng67@163.comPurpose: The aim of the present study was to develop an optimized Genkwanin (GKA)-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation to enhance the solubility, intestinal permeability, oral bioavailability and anti-colitis-associated colorectal cancer (CAC) activity of GKA.Methods: We designed a SNEDDS comprised oil phase, surfactants and co-surfactants for oral administration of GKA, the best of which were selected by investigating the saturation solubility, constructing pseudo-ternary phase diagrams, followed by optimizing thermodynamic stability, emulsification efficacy, self-nanoemulsification time, droplet size, transmission electron microscopy (TEM), drug release and intestinal permeability. In addition, the physicochemical properties and pharmacokinetics of GKA-SNEDDS were characterized, and its anti-colitis-associated colorectal cancer (CAC) activity and potential mechanisms were evaluated in AOM/DSS-induced C57BL/6J mice model.Results: The optimized nanoemulsion formula (OF) consists of Maisine CC, Labrasol ALF and Transcutol HP in a weight ratio of 20:60:20 (w/w/w), in which ratio the OF shows multiple improvements, specifically small mean droplet size, excellent stability, fast release properties as well as enhanced solubility and permeability. Pharmacokinetic studies demonstrated that compared with GKA suspension, the relative bioavailability of GKA-SNEDDS was increased by 353.28%. Moreover, GKA-SNEDDS not only significantly prevents weight loss and improves disease activity index (DAI) but also reduces the histological scores of inflammatory cytokine levels as well as inhibiting the formation of colon tumors via inducing tumor cell apoptosis in the AOM/DSS-induced CAC mice model.Conclusion: Our results show that the developed GKA-SNEDDS exhibited enhanced oral bioavailability and excellent anti-CAC efficacy. In summary, GKA-SNEDDS, using lipid nanoparticles as the drug delivery carrier, can be applied as a potential drug delivery system for improving the clinical application of GKA.Keywords: insoluble herbal drug, nanoparticle-based drug delivery system, intestinal permeability, pharmacokinetics, anticancer efficacy
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- 2021