Elucidating anticancer drugs release from UiO-66 as a carrier through the computational approaches.

The computational analysis of drug release from metal-organic frameworks (MOFs), specifically UiO-66, is the primary focus of this research. MOFs are recognized as nanocarriers due to their crystalline structure, porosity, and potential for added functionalities. The research examines the release patterns of three drugs: temozolomide, alendronate, and 5-fluorouracil, assessing various factors such as the drugs' distance from the UiO-66 centers, the interaction of drug functional groups with Zr metal ions, and the drug density throughout the nanocarrier. Findings reveal that 5-fluorouracil is located furthest from the UiO-66 center and exhibits the highest positive energy compared to the other drugs. Alendronate's density is observed to shift to the carrier surface, while 5-fluorouracil's density significantly decreases within the system. The drug density diminishes as the distance from the UiO-66 center of mass increases, suggesting a stronger positive interaction between the drugs and the nanocarrier. Moreover, Monte Carlo calculations were employed to load drugs onto the UiO-66 surface, leading to a substantial release of 5-fluorouracil from UiO-66. Quantum and Monte Carlo adsorption localization calculations were also conducted to gather data on the compounds' energy and geometry. This research underscores the potential of MOFs as nanocarriers for drug delivery and highlights the crucial role of temperature in regulating drug release from UiO-66. It provides insights into the complex dynamics of drug release and the factors influencing it, thereby emphasizing the promise of UiO-66 as a viable candidate for drug delivery. This work contributes to our understanding of UiO-66's role and sets the stage for improved performance optimization in the cancer treatment.

Interactions between ß-cyclodextrin as a carrier for anti-cancer drug delivery: a molecular dynamics simulation study.

A series of molecular dynamics simulations were performed on 5-fluorouracil (5-Fu), Alendronate (Ald), and Temozolomide (TMZ) anticancer drugs in the presence and absence of ß-cyclodextrin (ßCD) as a carrier. Thermodynamic investigations showed that the van der Waals interaction energy was dominant in loading all drugs inside the ßCD cavity. The sum of the interaction energies illustrated that the highest affinity was related to Ald (-136.5 kJ/mol), which in turn was due to the presence of bulky and charged atoms of phosphorus and oxygen, although TMZ (-115.92 kJ/mol) showed a very high affinity as well. At the same time, the hydrogen bond analysis also represented that Ald had the most hydrogen bond (1.97) with the highest half-life (3.13 ps) with ßCD. Investigation of the root mean fluctuation (RMSF) indicated that all the drugs had a relatively rigid structure and maintain this rigidity during loading in the ßCD cavity, and in the meantime, Ald was slightly more flexible than 5-Fu and TMZ. The area of ​the primary hydroxyl rim decreased in all drug-containing systems, which in turn was caused by the attractive interaction of drugs with oxygens in the primary hydroxyl rim. Especially for those drugs that were able to penetrate to the end of the primary hydroxyl rim of the ßCD, that means TMZ and 5-Fu. Meanwhile, due to the lack of Ald penetration to the end of the primary hydroxyl rim, the area change in the Ald-containing system was less than in the two others.Communicated by Ramaswamy H. Sarma.

A molecular dynamic simulation study of anticancer agents and UiO-66 as a carrier in drug delivery systems.

Targeted drug delivery systems are effective ways to reduce side effects and enhance the therapeutic efficacy of drugs. Metal-organic frameworks are a new class of porous materials that have been recently used as high-performance nanocarriers in medical applications, such as drug storage and delivery due to high internal surface area, high porosity, low toxicity, high payloads, controlled drug release, their exceptional biocompatibility, and biodegradability. In this study, the loading of anti-cancer drugs Temozolomide, Alendronate, and 5-Fluorouracil inside UiO-66 nanocarrier cavities at the atomic level and different concentrations of the drug were investigated using the molecular dynamics simulation method. Drug interaction energies with UiO-66, two-dimensional density map, and drug mobility in all systems were investigated. It was found that all drugs in higher concentration systems have higher loads than less concentrated systems. Among the drugs used, Temozolomide was located closer to the center of UiO-66 which indicated more negative interaction energy. Therefore, Temozolomide has a more thermodynamic tendency to load inside the UiO-66 cavities than the other studied drugs. Two-dimensional density study showed that all drugs were mainly loaded on metal centers. Temozolomide and Alendronate were loaded on inner centers, although 5-Fluorouracil showed a higher tendency to load on surface metal centers. From studying the mobility of drugs, Temozolomide was less mobile than the other two drugs due to its stronger interaction with UiO-66.