Exploring the mucoadhesive behavior of sucrose acetate isobutyrate: a novel excipient for oral delivery of biopharmaceuticals

Drug Delivery

Mathias Fanø¹  Lies A. L. Fliervoet²  Stine Harloff-Helleberg³  Hanne Mørck Nielsen³  Mechthild Schmitt⁴  Maxim Antopolski⁴  Arto Urtti⁵ 

[1]Bioneer: FARMA, University of Copenhagen, Universitetsparken 2, Copenhagen Ø, Denmark

[2]Department of Pharmaceutics, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, CG Utrecht, The Netherlands

[3]Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, Copenhagen Ø, Denmark

[4]Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Centre for Drug Research, University of Helsinki, Helsinki, Finland

[5]Division of Pharmaceutical Biosciences, Faculty of Pharmacy, Centre for Drug Research, University of Helsinki, Helsinki, Finland

[6]School of Pharmacy, University of Eastern Finland, Kuopio, Finlan

关键词: Sucrose acetate isobutyrate;    mucoadhesion;    rheology;    in vivo;    dynamic gastric model;    biopharmaceuticals;    oral drug delivery;    insulin;    mucoadhesion;    Caco-2 cells;   

DOI  :  10.1080/10717544.2019.1606866

来源: publisher

【 摘 要 】

Oral drug delivery is an attractive noninvasive alternative to injectables. However, oral delivery of biopharmaceuticals is highly challenging due to low stability during transit in the gastrointestinal tract (GIT), resulting in low systemic bioavailability. Thus, novel formulation strategies are essential to overcome this challenge. An interesting approach is increasing retention in the GIT by utilizing mucoadhesive biomaterials as excipients. Here, we explored the potential of the GRAS excipient sucrose acetate isobutyrate (SAIB) to obtain mucoadhesion in vivo. Mucoadhesive properties of a 90% SAIB/10% EtOH (w/w) drug delivery system (DDS) were assessed using a biosimilar mucus model and evaluation of rheological behavior after immersion in biosimilar intestinal fluid. To ease readability of this manuscript, we will refer to this as SAIB DDS. The effect of SAIB DDS on cell viability and epithelial membrane integrity was tested in vitro prior to in vivo studies that were conducted using SPECT/CT imaging in rats. When combining SAIB DDS with biosimilar mucus, increased viscosity was observed due to secondary interactions between biosimilar mucus and sucrose ester predicting considerable mucoadhesion. Mucoadhesion was confirmed in vivo, as radiolabeled insulin entrapped in SAIB DDS, remained in the small intestine for up to 22 h after administration. Moreover, the integrity of the system was investigated using the dynamic gastric model under conditions simulating the chemical composition of stomach fluid and physical shear stress in the antrum under fasted conditions. In conclusion, SAIB is an interesting and safe biomaterial to promote high mucoadhesion in the GIT after oral administration.

【 授权许可】

CC BY