Metal-organic gels: recent advances in their classification, characterization, and application in the pharmaceutical field.

Metal-organic gels (MOGs) are a type of functional soft substance with a three-dimensional (3D) network structure and solid-like rheological behavior, which are constructed by metal ions and bridging ligands formed under the driving force of coordination interactions or other non-covalent interactions. As the homologous substances of metal-organic frameworks (MOFs) and gels, they exhibit the potential advantages of high porosity, flexible structure, and adjustable mechanical properties, causing them to attract extensive research interest in the pharmaceutical field. For instance, MOGs are often used as excellent vehicles for intelligent drug delivery and programmable drug release to improve the clinical curative effect with reduced side effects. Also, MOGs are often applied as advanced biomedical materials for the repair and treatment of pathological tissue and sensitive detection of drugs or other molecules. However, despite the vigorous research on MOGs in recent years, there is no systematic summary of their applications in the pharmaceutical field to date. The present review systematically summarize the recent research progress on MOGs in the pharmaceutical field, including drug delivery systems, drug detection, pharmaceutical materials, and disease therapies. In addition, the formation principles and classification of MOGs are complemented and refined, and the techniques for the characterization of the structures/properties of MOGs are overviewed in this review.

Effect of Coformer Selection on In Vitro and In Vivo Performance of Adefovir Dipivoxil Cocrystals.

PURPOSE: This study aimed to improve the in vitro dissolution, permeability and oral bioavailability of adefovir dipivoxil (ADD) by cocrystal technology and clarify the important role of coformer selection on the cocrystal's properties. METHODS: ADD was cocrystallized with three small molecules (i.e., paracetamol (PA), saccharin (SAC) and nicotinamide (NIC)), respectively. The obtained ADD-PA cocrystal was characterized by DSC, TGA, PXRD and FTIR. Comparative study on dissolution rates among the three ADD cocrystals were conducted in water and pH 6.8 phosphate buffer. Besides, effects of coformers on intestinal permeability of ADD were evaluated via in vitro Caco-2 cell model and in situ single-pass intestinal perfusion model in rats. Furthermore, in vivo pharmacokinetic study of ADD cocrystals was also compared. RESULTS: Dissolution rates of ADD cocrystals were improved with the order of ADD-SAC cocrystal > ADD-PA cocrystal > ADD-NIC cocrystal. The permeability studies on Caco-2 cell model and single-pass intestinal perfusion model indicated that PA could enhance intestinal absorption of ADD by P-gp inhibition, while SAC and NIC did not. Further in vivo pharmacokinetic study showed that ADD-SAC cocrystal exhibited higher Cmax (1.4-fold) and AUC0-t (1.3-fold) of ADD than administration of ADD alone, and Cmax and AUC0-t of ADD-PA cocrystal were significantly enhanced by 2.1-fold and 2.2-fold, respectively, which was attributed to its higher dissolution and improved intestinal permeability. CONCLUSION: Coformer selection had an important role on cocrystal's properties, and cocrystallization of ADD with a suitable coformer was an effective approach to enhance both dissolution and bioavailability of ADD.