Computational modeling and molecular imprinting for the development of acrylic polymers with high affinity for bile salts

Abstract

This work has focused on the rational development of polymers capable of acting as traps of bile salts. Computational modeling was combined with molecular imprinting technology to obtain networks with high affinity for cholate salts in aqueous medium. The screening of a virtual library of 18 monomers, which are commonly used for imprinted networks, identified N-(3-aminopropyl)-methacrylate hydrochloride (APMA.HCl), N,N-diethylamino ethyl methacrylate (DEAEM) and ethyleneglycol methacrylate phosphate (EGMP) as suitable functional monomers with medium-to-high affinity for cholic acid. The polymers were prepared with a fix cholic acid:functional monomer mole ratio of 1:4, but with various cross-linking densities. Compared to polymers prepared without functional monomer, both imprinted and non-imprinted microparticles showed a high capability to remove sodium cholate from aqueous medium. High affinity APMA-based particles even resembled the performance of commercially available cholesterol-lowering granules. The imprinting effect was evident in most of the networks prepared, showing that computational modeling and molecular imprinting can act synergistically to improve the performance of certain polymers. Nevertheless, both the imprinted and non-imprinted networks prepared with the best monomer (APMA.HCl) identified by the modeling demonstrated such high affinity for the template that the imprinting effect was less important. The fitting of adsorption isotherms to the Freundlich model indicated that, in general, imprinting increases the population of high affinity binding sites, except when the affinity of the functional monomer for the target molecule is already very high. The cross-linking density was confirmed as a key parameter that determines the accessibility of the binding points to sodium cholate. Materials prepared with 9% mol APMA and 91% mol cross-linker showed enough affinity to achieve binding levels of up to 0.4 mmol g(-1) (i.e., 170 mg g(-1)) under flow (1 mL min(-1)) of 0.2 mM sodium cholate solution.

Cationic amphiphilic microfibrillated cellulose (MFC) for potential use for bile acid sorption

“…Cholate structure has both hydrophobic property (due to its steroid nucleus) and charge interaction potential (due to its ionic characteristics) (Rub et al, 2013), thus can have both hydrophobic interactions and electrostatic interactions with potential absorbents. Therefore, the sorption of cholate onto the modified CMFC can occur via the hydrophobic/hydrophobic interactions and electrostatic force, similar mechanism was proposed in the literature to account for the results of surface hydrophobized cellulose fibers as adsorbents for dissolved organic pollutants (Maatar et al, 2013), and those of acrylic polymers as adsorbents for bile acids (Yañez et al, 2010). Due to the self-assembly of sodium cholate (Rub et al, 2013), the diffusion of sodium cholate into the pores of cellulose was probably limited.…”

“…1). This provides the bile acids amphiphilic character and self-associative behavior (Yañez, Chianella, Piletsky, Concheiro, & Alvarez-Lorenzo, 2010 acid in the physiological condition of gut, which accordingly makes it an attractive material for food supplement for people with high cholesterol.…”

Molecularly Imprinted Polymers

“…The latter technique uses molecular modeling software to screen a virtual library of monomers for a given template. Monomers that form the most stable complex with the template, sometimes taking into account the solvent used, are identified, and the corresponding MIPs are synthesized for experimental confirmation [17][18][19]. The use of NMR titration or other spectroscopic methods as standalone technique or for the confirmation of modeling results [20][21][22][23] may seem obvious, but is not routinely done as yet.…”

Stimuli–responsive networks grafted onto polypropylene for the sustained delivery of NSAIDs

“…The grafted surface behaved as a temperature-responsive network, due to poly(NIPAAm), which swells at room temperature, enabling fast loading of the drug, but shrinks at body temperature, sustaining drug release [24,25]. Furthermore, polyAPMA can electrostatically interact with anionic drugs, driving uptake, as well as improving the hemocompatibility of the films [26][27][28][29]. The aim of this work was to gain an insight into the blood compatibility, cytocompatibility and frictional properties of grafted PP materials, which are very relevant to the reaction of the host to the foreign body material and to evaluate their ability to load therapeutic doses of non-steroidal anti-inflammatory drugs (NSAIDs) and sustain their release for prolonged periods.…”