Akademik Veri Yönetim Sistemi
Journal of Drug Delivery Science and Technology, cilt.104, 2025 (SCI-Expanded)
The oral route is undoubtedly the most preferred route among of drug administration routes of due to its various advantages and high patient compliance. γ-CD-based metal-organic frameworks (γ-CD-MOFs) offer a new platform for enhancing drug solubility due to their high surface area, adjustable pore size, and tunable inner surface properties. The major aim of this study was to investigate the effects of γ-CD-MOFs on permeation by increasing the solubility of tamoxifen citrate (TMX), a BCS class II drug. The second goal of the study is to highlight the effect of particle size of γ-CD-MOFs on the solubility and, more importantly, the permeability of TMX. For this purpose, γ-CD-MOFs were synthesized via two different modified methanol diffusion methods using PEG20000 and TMX-γ-CD-MOFs were obtained via impregnation method. TMX-γ-CD-MOFs were fully characterized and their solubility, in vitro release, cytotoxicity, permeation through Caco-2 cell monolayers, and stability properties were evaluated in comparison with free tamoxifen and the γ-CD/TMX physical mixture. The particle sizes of γ-CD-MOF-1 and γ-CD-MOF-2 were measured as 606.3 ± 38.40 nm and 337.8 ± 31.86 nm, respectively, and as expected, the particle size increased to 998.7 ± 82.95 nm and 608.3 ± 172.70 nm, respectively, upon TMX loading. Solubility studies were conducted in water and at physiological pH, simulating gastrointestinal conditions, and the γ-CD-MOF formulations exhibited higher solubility than TMX and the physical mixture. TMX-γ-CD-MOF-2 was shown to be superior to TMX-γ-CD-MOF-1 in enhancing solubility, indicating the importance of the particle size of γ-CD-MOFs. Both TMX-γ-CD-MOF formulations improved the in vitro TMX release rate, with TMX-γ-CD-MOF-2 reaching 100 % while TMX-γ-CD-MOF-1 remained at 78 % at the end of 24 h. γ-CD-MOFs were exhibited no infavorable effect on viability of Caco-2 cells. TMX-γ-CD-MOF-1 increased permeability by 2.24-fold and TMX-γ-CD-MOF-2 by 3.57-fold compared to TMX. All the studies conducted demonstrated that the γ-CD-MOFs, especially TMX-γ-CD-MOF-2 were successful in improving the solubility, in vitro release, and permeability properties of TMX. γ-CD-MOFs suggest a promising nanoscale platform for not only increasing drug solubility, but also for obtaining controlled drug release and enhanced permeability for BCS II and IV drugs, which is mainly affected by particle size.