Rationalization of the entrapping of bioactive molecules into a series of functionalized porous zirconium terephthalate MOFs.

The encapsulation of two different bioactive molecules, the cosmetic caffeine and the analgesic and anti-inflammatory ibuprofen, has been evaluated by combining impregnation and advanced characterization experimental tools in a series of microporous rigid zirconium(iv) terephthalates UiO-66 bearing different polar or apolar functional groups (-H, -Br, -NH2, -2OH, -NO2, -Cl, -2CF3, -CH3, -2CH3). It has been first evidenced that these hybrid solids exhibit drug payloads that significantly outperform those obtained using current drug formulations or other conventional porous solids. A quantitative structure-activity relationship strategy has been further conducted with the aim of rationalizing the experimental drug uptakes and further emphasizing the most relevant chemical and structural features that significantly impact their encapsulation performances. Indeed, it appears that the caffeine loading is optimized when the functionalized organic linker both shows a large octanol-water partition coefficient and contains grafted functions with low hydrogen bond acceptor abilities, whereas the ibuprofen entrapping is enhanced when the organic linker contains functional groups with a large solvent surface area and free volume, and to a lesser extent low hydrogen bond acceptor abilities. Moreover, it has been shown that the solvent used as media for the biomolecule impregnation plays a crucial role in the encapsulation performance due to the formation of a competitive adsorption process between the solvent and the active molecule.

Effect of chitosan coating on the swelling and controlled release of a poorly water-soluble drug from an amphiphilic and pH-sensitive hydrogel.

In the present work, a new particulate controlled release system was prepared, by coating alginate-g-PCL/Ca(2+) beads with chitosan. The swelling behaviour and controlled release of a poorly water-soluble drug (theophylline) model were studied in media of varying pH, by simulating human fluids at 37 degrees C. In a simulated gastric fluid (SGF, pH 1.2), coated beads presented weak swelling (8-22%) and weak release rates (24-32% within 120min), and were able to protect the drug from this harsh environment. In a simulated intestinal fluid (SIF, pH 6.8), the swelling rates of amphiphilic beads (before disintegration) were strongly reduced (300-1100%) comparatively with those of uncoated beads (700-1700%). This can be explained by the strong electrostatic interactions between the amino groups of chitosan and the carboxylate groups of alginate-g-PCL, leading to the formation of a protective membrane of strong polyelectrolyte complex around the beads. This outermost layer effectively promoted the stability of beads under gastro-intestinal tract conditions, while the hydrophobic interactions between theophylline and PCL grafts allowed a considerable slowing down of the drug release. It was found out that combination of the protective effect of the polyelectrolyte membrane in SIF associated with the hydrophobicity of PCL grafts allowed to release a poorly water-soluble drug, in a controlled manner, for 7h, along a simulated gastro-intestinal tract.

New amphiphilic and pH-sensitive hydrogel for controlled release of a model poorly water-soluble drug.

This paper presents the development of new pH-sensitive, amphiphilic and biocompatible hydrogels based on alginate-g-PCL, cross-linked with calcium ions to form beads, prepared for controlled delivery of poorly water-soluble drug. We have focused our study on the effect of the length of PCL chains (530 and 1250 g mol(-1)). Swelling profiles obtained clearly indicated that these hydrogels swell slightly (10-14%) in a simulated gastric fluid (pH 1.2), and strongly (700-1300% before disintegration) in a simulated intestinal fluid (pH 6.8). In both media, rates of swelling were lower for beads based on amphiphilic derivatives than for alginate/Ca2+ ones due to the hydrophobic PCL grafts, and decreased when hydrophobic character increased. A model drug, theophylline, was entrapped into these hydrogels and release studies were carried out. The drug was protected in acidic fluid (only 14-20% of release for alginate-g-PCL hydrogel against 35% of release for alginate hydrogel during 350 min). The drug is released completely in neutral fluid due to ion exchanges and disintegration of the hydrogel. PCL leads to decrease in the release kinetics in SIF (2h for alginate-g-PCL/Ca2+ beads against 1h for alginate/Ca2+ beads). It was demonstrated that the establishment of clusters inside beads by intramolecular interactions between PCL grafts of 530 g mol(-1) in salt media allowed to retain the drug and to slow down its release considerably.