Abstract
The present work reports the effect of polysaccharides (chitosan and sodium alginate) on silica nanoparticles (SiNP) for hydrophilic molecules delivery taking insulin as model drug. The influence of tetraethyl orthosilicate (TEOS) and homogenization speed on SiNP properties was assessed by a 22 factorial design achieving as optimal parameters: 0.43 mol/L of TEOS and homogenization speed of 5000 rpm. SiNP mean particle size (Z-Ave) was of 256.6 nm and polydispersity index (PI) of 0.218. SiNP coated with chitosan (SiNP-CH) or sodium alginate (SiNP-SA) increased insulin association efficacy; reaching 84.6% (SiNP-SA) and 90.8% (SiNP-CH). However, coated SiNP released 50–60% of the peptide during the first 45 min at acidic environment, while uncoated SiNP only released ~30%. Similar results were obtained at pH 6.8. The low Akaike’s (AIC) values indicated that drug release followed Peppas model for SiNP-SA and second order for uncoated SiNP and SiNP-CH (pH 2.0). At pH 6.8, the best fitting was Boltzmann for Ins-SiNP. However, SiNP-CH and SiNP-SA showed a first-order behavior. Cytotoxicity of nanoparticles, assessed in Caco-2 and HepG2 cells, showed that 100 to 500 µg/mL SiNP-CH and SiNP-SA slightly decreased cell viability, comparing with SiNP. In conclusion, coating SiNP with selected polysaccharides influenced the nanoparticles physicochemical properties, the insulin release, and the effect of these nanoparticles on cell viability.
Highlights
The oral ingestion of therapeutic drugs is the preferred route of administration, the development of oral drug delivery systems is encountering serious limitations such as, high molecular weight and poor permeability across the gastrointestinal epithelium resulting in low bioavailability of orally administered drugs [1,2]
Oroval et al, (2017) reported that β-cyclodextrin-modified enzyme glucose oxidase used as gatekeepers in mesoporous silica nanoparticles (MSiNP) for insulin release showed to be sensitive to the glucose concentration [18]
Taking into account the chemical versatility of silica nanoparticles (SiNP) associated to their surface modification facilities and their ability to conjugate to hydrophilic molecules, the main aim of the present study was to compare the effect of mucoadhesive compounds, such as polysaccharides on the properties of SiNP for hydrophilic drug delivery, using insulin as model biomolecule
Summary
The oral ingestion of therapeutic drugs is the preferred route of administration, the development of oral drug delivery systems is encountering serious limitations such as, high molecular weight and poor permeability across the gastrointestinal epithelium resulting in low bioavailability of orally administered drugs [1,2]. The degradation of therapeutic protein molecules can be carried out by the stomach enzymes, such as pepsin and by the intestinal enzymes, such as trypsin, chymotrypsin and carboxypeptidases, and by the environmental pH [3] To overcome such obstacles and increase the oral bioavailability of the therapeutic molecules, a wide range of strategies using different type of nanoparticles as drug delivery carriers has been adopted as shown in several works [4,5,6,7]. Mucoadhesive drug-delivery systems are based on the ability of bioadhesion of the certain natural or synthetic material to adhere to mucus membranes [21], targeting a drug to a particular mucus tissue for an extended period of time Hydrophilic polysaccharides, such as chitosan or sodium alginate, have been widely used to improve the penetration of loaded proteins/peptides in the intestinal mucosa due to the mucoadhesive and absorption-enhancing properties of the former [22]
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