Surface Interactions between Ketoprofen and Silica-Based Biomaterials as Drug Delivery System Synthesized via Sol–Gel: A Molecular Dynamics Study

Abstract

Biomaterial-based drug delivery systems for a controlled drug release are drawing increasing attention thanks to their possible pharmaceutical and biomedical applications. It is important to control the local administration of drugs, especially when the drug exhibits problems diffusing across biological barriers. Thus, in an appropriate concentration, it would be released in situ, reducing side effects due to interactions with the biological environment after implantation. A theoretical study based on Molecular Mechanics and Molecular Dynamics methods is performed to investigate possible surface interactions between the amorphous SiO2 surface and the ketoprofen molecules, an anti-inflammatory drug, considering the role of drug concentration. These theoretical results are compared with experimental data obtained by analyzing, through Fourier transform infrared spectroscopy (FT-IR), the interaction between the SiO2 amorphous surface and two percentages of the ketoprofen drug entrapped in a silica matrix obtained via the sol–gel method and dried materials. The loaded drug in these amorphous bioactive material forms hydrogen bonds with the silica surface, as found in this theoretical study. The surface interactions are essential to have a new generation of biomaterials not only important for biocompatibility, with specific structural and functional properties, but also able to incorporate anti-inflammatory agents for release into the human body.

L-Arginine-Derived Polyamidoamine Oligomers Bearing at Both Ends β-Cyclodextrin Units as pH-Sensitive Curcumin Carriers

“…Using a simulation protocol proposed in previous work [ 20 , 21 , 22 , 23 , 24 , 25 ], after the initial energy minimizations of the simulation cells having 20 curcumin molecules and 10 P3 or P5 molecules in the initial random arrangements, four different MD runs of the systems at two different pH values (pH 7.4 and 4.5) lasting 50 ns were performed. It is worth underlining here that the random arrangement in the simulation cell corresponds to the hypothesis of initial complete solubilization in water of all involved molecules.…”

“…In the aggregates, the curcumin molecules involved in host–guest inclusion complexes, compared to those exposed on the outer surface, probably influence the drug release kinetics by slowing it down. Indeed, it was previously observed in the case of piroxicam/β-CD nanosponges [ 23 ] that drug molecules located on the outer surface were released faster and those forming host–host inclusion complexes more slowly.…”

“…These simulations are performed using the consistent valence force field (CVFF) [ 37 ] and the Materials Studio packages [ 38 ]. The simulation protocol is the same adopted in the previous work [ 20 , 21 , 22 , 23 , 24 , 25 ]. This protocol provides (i) the initial energy minimization, (ii) MD runs until the equilibrium state was achieved (iii) final geometry optimizations of the final configuration and of some different configurations assumed by the system during MD run.…”

“…In the last 20 years, CDs and their complexes have shown self-association processes in solution to form aggregates or micelle-like structures [ 18 , 19 ]. Furthermore, theoretical studies based on molecular mechanics (MM) and molecular dynamics (MD) simulations have proven to be powerful tools to explain at the atomistic level the stability and the conformation of different native or functionalized CDs, the geometry of host-guest inclusion complexes and β-CD nanosponges in good agreement with the NMR experimental data [ 20 , 21 , 22 , 23 , 24 , 25 ].…”

Hybrid Organic–Inorganic Biomaterials as Drug Delivery Systems: A Molecular Dynamics Study of Quercetin Adsorption on Amorphous Silica Surfaces

“…In a previous study, the molecules of the drug ketoprofen, a poorly soluble inflammatory drug [69], were encapsulated in a silica matrix via the Sol-Gel method [70][71][72][73][74][75][76]. After FT-IR experiments [77] related to drug-loaded silica-based biomaterials, the adsorption of the drug ketoprofen on amorphous SiO 2 surfaces was confirmed considering two different concentrations, with two different release kinetics faster at relatively higher concentrations. Using theoretical Molecular Mechanics (MM) and Molecular Dynamics (MD) methods and a specific simulation protocol proposed for the adsorption process on the hydrated and dried surface [70,77], favorable non-covalent interactions at the external surface are confirmed.…”