Interaction between porous silica gel microcarriers and peptides for oral administration of functional peptides

Abstract

Functional peptides, peptides that have biological activities, have attracted attention as active ingredients of functional foods and health foods. In particular, for food applications, because orally ingested peptides are degraded by digestive enzymes in the stomach, novel oral administration methods that can prevent peptide degradation and successfully deliver them intestinally are desired. In the present study, we focused on porous silica gel, which has many useful characteristics, such as large surface area, pH responsive functional groups, size controllable pores, and approval as food additives. We investigated the possibility of using porous silica gel as a peptide degradation protective microcarrier. As a result, we found that heat treatment of the silica gel at 600 °C for 2 h remarkably enhanced the adsorbed amount of many peptides under acidic conditions, and negatively charged and highly hydrophobic peptides had suitable characteristics for oral intestinal delivery with silica gel. Finally, we demonstrated the degree of protection from pepsin degradation and found that the protection of DFELEDD peptide was 57.1 ± 3.9% when DFELEDD was mixed with the heat-treated silica gel. These results indicated that the heat-treated silica gel is promising for efficient oral intestinal delivery of hydrophobic negatively charged peptides.

Selective Elimination of Bitter Peptides by Adsorption to Heat-treated Porous Silica Gel

“…Peptide library synthesis Peptide arrays were synthesized using a cellulose membrane and a spot synthesizer (Intervis, ASP222, Cologne, Germany) as previously described (Imai et al, 2018). After punching, the individual resulting peptidecontaining disks (peptide spots) were placed in the single wells of a 96-well plate filter (MSRLN0410; Merck Millipore, Burlington, MA, USA) and 180 μL of PBS (phosphate buffered saline) was added to each well.…”

“…We found that the adsorption properties were summarized by pI and the hydrophobicity of peptides, and under neutral conditions, the remaining silanol groups are deprotonated and negatively charged. Thus, hydrophobic or positively charged peptides were highly adsorbed due to hydrophobic and electrical interaction (Imai et al, 2018). Color maps of peptide adsorption ratios to heat treated silica gel under pH 7.4 condition (3-mer, 5-mer and 7-mer peptides).…”

“…The higher score indicates the better adsorbing peptide. The detailed method of creating color map is referred by our previous report (Imai et al, 2018). Most bitter peptides possess hydrophobic or basic properties; thus, we hypothesized that our silica gel could be employed as a new material to selectively remove bitter peptides.…”

In Silico Screening of a Bile Acid Micelle Disruption Peptide for Oral Consumptions from Edible Peptide Database

“…Orally ingested peptides are inactivated by the action of digestive enzymes, such as peptidases and proteases in the stomach [12]. To overcome this problem, a heat-treated porous silica gel (HT silica gel) was developed that has an average pore size of 10 nm and a hydrophobic surface that changes depending on the environmental pH [13]. Using the HT silica gel, approximately 60% of the peptides located inside and/or on the surface of the HT silica gel were protected from pepsin proteolysis at pH 2.0.…”

“…Consequently, it was concluded that the HT silica gel preferably desorbed hydrophobic and negatively charged peptides at pH 7 (intestinal environment), and the peptides with such properties enabled direct delivery to the intestinal space. To evaluate the intestinal delivery activity of any peptide, a 3D color map was designed, which consists of the physicochemical properties of peptides and intestinal delivery score [13]. In a subsequent study, dual-functional peptides were developed [14], which have properties for direct intestinal delivery and bile acid-binding activity, utilizing the analysis of residuesubstituted peptides of parent peptide, VAWWMY [15].…”