Modulation of Methotrexate Release from Nano-Hydrogels via Drug-Transition Metal Complexation
سال انتشار: 1399
نوع سند: مقاله ژورنالی
زبان: انگلیسی
مشاهده: 251
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شناسه ملی سند علمی:
JR_TIPS-6-3_001
تاریخ نمایه سازی: 22 دی 1399
چکیده مقاله:
Despite the extensive application of methotrexate (MTX) as a chemotherapeutic agent and an immune system suppressor, its therapeutic implementation has been limited due to its poor pharmacokinetics, saturable cellular transport, and insufficient response in some conditions. These limitations have resulted in the development of novel formulations. A pH-dependent MTX release was indicated in our previous study on polyethyleneimine nano-hydrogels; however, it exhibited a fast drug release in phosphate-buffered saline simulating physiologic pH and tonicity conditions. Thus, the current study was aimed at the synthesis of Zn(MTX)2Cl2 complex (MTX-Zn) to modulate drug loading and release under physiologic condition (pH=7.4). MTX-Zn was synthesized by the hydrothermal method and characterized by TLC, FT-IR spectroscopy, and Eriochrome Black T complexometric titration. MTX-Zn was then loaded into the nano-hydrogels and purified through ultrafiltration. The final product was evaluated by DLS, Zeta-potential, and TEM. The variations in the drug loading and release in acidic (tumor) and physiologic media were assessed through UV-Vis spectrophotometry and dialysis methods, respectively. A 5-fold enhancement was observed in the MTX solubility in the acetate buffer; while the Log D value increased from -0.66 to 0.1 upon Zn2+ complexation, reflecting an augmentation in the drug lipophilicity. The MTX-Zn loaded nano-hydrogels exhibited desirable physicochemical features like a small hydrodynamic diameter of 125.7 nm and low polydispersity (PDI = 0.14). The results indicated that, the release tests indicated that the release of MTX-Zn involves a combination of diffusion and swelling mechanisms. MTX-Zn complexation can be applied in the sustained drug release from the nano-hydrogel formulations.
کلیدواژه ها:
نویسندگان
Mahsa Taheri
Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran
Mozhgan Abedanzadeh
Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran
Samaneh Mohammadi
Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran
Sanaz Javanmardi
Center for Nanotechnology in Drug Delivery, Shiraz University of Medical Sciences, Shiraz, Iran
Alimohammad Tamaddon
Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz ۷۱۳۴۵, Iran