Abstract
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.
Highlights
Sucrose acetate isobutyrate (SAIB) is commonly used as an emulsion stabilizer in soft drinks and has been shown to remain in the gastrointestinal tract (GIT) for up to 24 h (Phillips et al, 1976), due to both limited absorption and degradation
When utilizing the sucrose acetate isobutyrate (SAIB) drug delivery system (DDS) as a potential biomaterial, knowledge about its rheological properties is important, as they closely relates to drug release behavior (Szu}ts et al, 2008, 2010), spreading and adhesion on the mucosa, residence time in vivo (Carlfors et al, 1998; Edsman et al, 1998; Desai & Blanchard, 2000; Chang et al, 2002) and microstructural stability (Partal et al, 1997)
When running rheological analysis at 22 C, SAIB DDS stored at 37 C is characterized by a higher G0 compared to the SAIB DDS stored at lower temperatures (5 and 22 C, Figure 2(A)) and considerably more stress was needed to cause a 10% decrease in G0 after storage at 37 C, when comparing the samples tested (Supplementary data)
Summary
Sucrose acetate isobutyrate (SAIB) is commonly used as an emulsion stabilizer in soft drinks and has been shown to remain in the gastrointestinal tract (GIT) for up to 24 h (Phillips et al, 1976), due to both limited absorption and degradation. The potential of using SAIB has been studied in injectable drug delivery systems (DDSs) for small molecules (Lee et al, 2006; Lu et al, 2008; Wang et al, 2018). In those studies, SAIB was used to form a water insoluble, yet biodegradable, matrix when mixed with 10% ethanol resulting in a matrix from where the investigated drugs were released in a sustained manner. Successful oral delivery may, be greatly challenged by the low stability of drugs in the gastrointestinal (GI) tract, especially for peptides, proteins, and other biopharmaceuticals, which represents a growing part of the pharmaceutical portfolio (Hamman et al, 2005). Much work has been done to overcome these obstacles, utilizing various strategies to Supplemental data for this article can be accessed here
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
