(224b) Computational Investigations of Drug Storage and Delivery in Bio-Compatible Nanoporous Materials

Encapsulation of drug molecules is required to improve the drug bio-distribution, the biological half-life of the active species and therapeutic effect of the drug.[1] Lipids, polymeric nanoparticles, metal clusters and carbon structures have been tested as drug storage materials but these materials have several limitations such as low drug loading capacities (<5 wt%), rapid drug release and toxicity.[2] Recently, metal organic frameworks (MOFs), a new group of nanoporous materials, have been studied in drug and cosmetic molecule storage applications due to their large surface areas, high pore volumes and tunable pore sizes and several MOFs are identified as promising materials for drug storage.[3] However, considering the very large number of available MOFs, it is not practical to assess the potential of each MOF in drug storage applications using purely experimental manners. Computational methods that can rapidly predict drug storage capacity of MOFs prior to experimental studies would be highly useful to identify the materials with the highest performances. However, there is almost no information about the drug storage performances of different types of MOFs. This lack of information also limits understanding the relation between drug storage performances of MOFs and their structural properties.

In this work, we studied both adsorption and diffusion of representative drug and cosmetic molecules in various bio-compatible MOFs. Ibuprofen (an analgesic and anti-inflammatory drug) was chosen as a representative drug molecule, caffeine (lipo-reducer) and urea (hydrating agent) were considered as representatives of cosmetic molecules. Ibuprofen, caffeine and urea storage performances of 24 different bio-compatible MOFs were examined using configurational bias Monte Carlo (CBMC) simulations. Once a drug molecule is captured by a MOF, it has to be delivered to the target cells and released over a long period of time to increase its therapeutic effect. Short delivery time is not desired since in this case drug release occurs prior to reach to targeted cells. Therefore, release performance of materials must be also examined in order to identify the best performing materials as drug carriers. With this aim, we performed molecular dynamics simulations to examine ibuprofen, caffeine and urea diffusion in a MOF that showed high storage performance. Both rigid and flexible MOF structures were used in diffusion simulations to understand the effect of structure flexibility on the drug/cosmetic molecule diffusion. We also studied the effect of water on diffusion of drug and cosmetic molecules since these molecules are generally encapsulated in a liquid environment in practical applications. Finally, effects of MOFsâ?? structural properties such as pore volume and pore size on the drug storage and diffusion were investigated to provide information on the materialsâ?? structure-performance relationships.[4] This study showed that bio-compatible MOFs have strong potential in drug storage and delivery and they can be alternatives to traditional drug carriers. The computational methodology that we described here will be helpful to identify the most promising MOFs among many of them for drug/cosmetic storage prior to extensive experimental efforts.

Acknowledgment: Financial supports provided by the TUBITAK 2211-C Scholarship Program. S.K. acknowledges TUBA-GEBIP Programme.

*Corresponding author: skeskin@ku.edu.tr

References:

[1] C. Tamames-Tabar et al., MOFs in Pharmaceutical Technology. In Bio- and Bioinspired Nanomaterials, Wiley-VCH Verlag GmbH & Co. KGaA: Germany, 2014.

[2] P. Horcajada et al., Chem. Rev. 112, No. 2, 1232 (2011).

[3] G. Férey et al., Science, 309, No. 5743, 2040 (2005).

[4] I. Erucar and S. Keskin, Ind. Eng. Chem. Res., 55, No. 7, 1929 (2016).