Enhanced Bioavailability of Polyaromatic Hydrocarbons in the Form of Mucin Complexes

Abstract

Increasing exposure of biological systems to large amounts of polycyclic aromatic hydrocarbons is of great public concern. Organisms have an array of biological defense mechanisms, and it is believed that mucosal gel (which covers the respiratory system, the gastrointestinal tract, etc.) provides an effective chemical shield against a range of toxic materials. However, in this work, we demonstrate, for the first time, that, upon complexation of polyaromatic hydrocarbons with mucins, enhanced bioavailability and, therefore, toxicity are obtained. This work was aimed to demonstrate how complexation of various highly hydrophobic polycyclic aromatic hydrocarbons with representative mucin glycoprotein could lead to the formation of previously undescribed materials, which exhibit increased toxicity versus pristine polycyclic aromatic hydrocarbons. In the present work, we show that a representative mucin glycoprotein, bovine submaxillary mucin, has impressive and unprecedented capabilities of binding and solubilizing water-insoluble materials in physiological solution. The complexes formed between the mucin and a series of polycyclic aromatic hydrocarbons were comprehensively characterized, and their toxicity was evaluated by both in vivo and in vitro assays. In addition, the bioavailability and membrane-penetration capabilities were tested using an internalization assay. Our results provide, for the first time, evidence of an unknown route by which hydrophobic materials may achieve higher bioavailability, penetrating some of the biological defense systems, in the form of water-soluble complexes with mucosal proteins.

Covalently-crosslinked mucin biopolymer hydrogels for sustained drug delivery

“…Here, 29 we demonstrate that mucin glycoproteins, the gel-forming constituents of native mucus, are suitable for 30 assembly into robust hydrogels capable of facilitating the sustained release of hydrophobic and hydrophi- 31 lic drugs. Covalently-crosslinked mucin hydrogels were generated via exposure of methacrylated mucin 32 to ultraviolet light in the presence of a free radical photoinitiator.…”

“…We characterize mucin hydro-123 gels rheologically and investigate the loading and release from 124 mucin hydrogels of polymyxin B, a positively-charged hydrophilic 125 antibacterial drug, and paclitaxel, a hydrophobic anti-cancer drug. 126 We demonstrate the sustained release from mucin hydrogels of [30] as well as binds 344 and solubilizes water-insoluble aromatic hydrocarbons, enhancing 345 their bioavailability [31]. 346 We methacrylated BSM following methacrylation protocols 347 previously applied to other biopolymers, including gelatin 348 [32,33], dextran [34], chitosan [35], chondroitin sulfate [36], and 349 hyaluronic acid [37], but never before to mucin.…”

Silver Nanoparticles Complexed with Bovine Submaxillary Mucin Possess Strong Antibacterial Activity and Protect against Seedling Infection

“…Among their chemical properties, mucins may act as moisture holders, adhesins, and solubilizers, as well as reducing agents and surfactants (18). Some of us have shown that BSM, a representative natural mucin, is capable of binding and solubilizing various types of polycyclic aromatic hydrocarbons in aqueous solutions, leading to increased antimicrobial activity (19). Further, a simple method was developed to generate Ag NPs inside a BSM matrix (20).…”

Triflic Acid Mediated Cascade Cyclization of Aryldiynes for the Synthesis of Indeno[1,2‐c]chromenes: Application to Dye‐Sensitized Solar Cells

“…23 We have shown that the guest concentrations of dyes or MWNT could be as high as 17 % 23. 24 Fluorescent BSM solutions and electro‐optical devices were prepared with the use of several types of hydrophobic emitting dye molecules as fillers.…”