β-lactoglobulin-irinotecan inclusion complex as a new targeted nanocarrier for colorectal cancer cells

Abstract

Beta-lactoglobulin (β-LG) is a lipocalin family member whose general function appears to be solubilizing and transport of hydrophobic molecules. Some properties such as avalability, ease of purification, and peculiar resistance to acidic environments can make β-LG as a carrier for hydrophobic and acid labile drugs for oral administration. In this protein vehicle, drug could be protected in acidic environment of stomach and then released within the basic small intestine. In this study, the potential of β-LG as a nanocarrier for oral delivery of a potent agent in colorectal cancer treatment, irinotecan, was evaluated. The nanoparticle was prepared by the physical inclusion complex method. Size, drug loading, encapsulation efficiency, and in vitro drug release at various pH values were investigated. The optimum formulation showed a narrow size distribution with an average diameter of 139.86 ± 13.75 nm and drug loading about 84.33 ± 5.03%. Based on the results obtained from docking simulation of irinotecan-complex, there are two distinct binding sites in this nanocarrier. Cytotoxicity of this nanocarrier on the HT-29 cancer cell line and AGS was measured by MTT assay. The cytotoxicity experiment showed that the drug-loaded nanocarrier was more effective than free drug. The higher release percent of drug from the β-LG complex at pH 7.4 compared to pH 1.2 indicated that the proposed nanocarrier could be introduced as a suitable nanovehicle for labile drugs in acidic medium targeted for colorectal segment.

A role of heparan sulphate proteoglycan in the cellular uptake of lipocalins ß-lactoglobulin and allergen Fel d 4

“…Since HSPGs are ubiquitously expressed by most mammalian cell types, such heparin-binding lipocalins may enter numerous cells. This finding is of special interest as BLG has been recently used as a nanocarrier for delivering biological agents such as chemotherapeutics (Bijari et al 2019;Shafaei et al 2017), and has also been attributed cytoproliferative effects (Tai et al 2016). In addition, it was demonstrated that antigens with inherent heparin-binding affinity are supported more efficiently by the immune system (Léonetti et al 2010), an effect which might shed some light on the enigmatic allergenicity of lipocalins.…”

“…Both lipocalins are relevant human allergens. In addition, BLG was demonstrated to be a potent stimulator of proliferation (Tai et al 2016) and is used as a nanocarrier for delivering pharmacological agents (Bijari et al 2019;Shafaei et al 2017). Therefore, in this work we aimed to identify cell surface components responsible for the cellular uptake of these lipocalins.…”

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“…The interaction between atenolol and βcyclodextrin was observed by the FT-IR transmission spectrum of atenolol, β-cyclodextrin, and inclusion complex using the potassium bromide (KBr) disc technique 2,14 . All the spectrum acquired were scanned between 400 and 4000 cm -1 .…”

“…The crystallographic state of atenolol, β-cyclodextrin, and an inclusion complex of atenolol-βcyclodextrin was investigated using X-ray diffractometer (Phillips) in the range 2Ө (5-50°) at room temperature 14 .…”

“…An inclusion complex of atenolol and β-cyclodextrins is promising to develop in order to increase the solubility of atenolol, hence the dissolution rate of atenolol will be enhanced. Moreover, an inclusion complex of atenolol with βcyclodextrinsis also giving opportunities for pre gastric absorption of atenolol 14 . An inclusion complex of atenolol with β-cyclodextrin in 1:1 ratio was the best ratio, based on the evidence from previous studies 15 .…”