Abstract
Objective: The objective of the present study is to synthesize and optimize gemcitabine (GEM)-loaded MIL-101NH2 (Fe) nanocarriers. The design of experiments is used to optimize the formulation for higher encapsulation efficiency (EE) for effective drug delivery.
 Materials and Methods: MIL-101NH2 (Fe) was synthesized by microwave-assisted hydrothermal method. Central composite design (CCD) under response surface methodology was used for the optimization of GEM encapsulation into the MIL-101NH2 (Fe). The most influential variable that affects the EE was investigated by Perturbation plot. Validation of the design was carried out by performing the experiments under optimal conditions. Further optimized formulation was physicochemically characterized for particle size, surface charge, and surface morphology using zetasizer and scanning electron microscopy (SEM), respectively. Structural integrity of the optimized formulation was carried out by Powder X ray crystallography (PXRD). Fourier-transform infrared (FTIR) spectroscopy was used for the confirmation of GEM loading. Accelerated storage stability analysis was also performed to find out the related parameters.
 Results: Here in this work, crystalline MIL-101NH2 (Fe) has been successfully synthesized by microwave radiation method. The optimization result revealed that process variables such as GEM concentration, pH, and time significantly affect the desired constraint, EE. Perturbation plot evidenced that among all the variables, pH is the most significant factor followed by drug concentration and time. The optimized formulation exhibited 76.4 ± 7% EE and average particle size of 252.9 ± 9.23 nm. PXRD and SEM results demonstrated that the optimized formulation was crystalline in nature. FTIR spectroscopy confirms the presence of drug inside the MIL-101NH2 (Fe). In vitro release profile revealed that MIL-101NH2 (Fe)-GEM exhibited the sustained release up to 72 h in comparison to the native GEM. Storage-stability studies also indicate that MIL-101NH2 (Fe)-GEM has a shelf life of 6 months.
 Conclusion: The EE of GEM in MIL-101NH2 (Fe) can be altered by varying the drug concentration and pH during the impregnation.
Highlights
Drug gemcitabine (GEM) is one among the Food and Drug Administrative authority- approved drugs, which is mainly used for the first-line therapy for advanced and metastatic pancreatic cancer [1,2,3]
The optimization result revealed that process variables such as GEM concentration, pH, and time significantly affect the desired constraint, EE
Powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) results demonstrated that the optimized formulation was crystalline in nature
Summary
Drug gemcitabine (GEM) is one among the Food and Drug Administrative authority- approved drugs, which is mainly used for the first-line therapy for advanced and metastatic pancreatic cancer [1,2,3] It is a difluoro analog of deoxycytidine which is transported to cells by nucleoside transporters, where it is phosphorylated to difluorodeoxycytidine diphosphate (dFdCDP, ribonucleotide reductase inhibitor) and triphosphate (dFdCTP, compete with cytidine phosphate). Several liposomal formulations have been prepared and evaluated, e.g., pH-sensitive stearoylPEG-poly(methacryloyl sulfadimethoxine)-coated liposomes [17] and hyaluronic acid-coated liposomes for pancreatic adenocarcinoma cells [18] Among these approaches, liposomes were the most effective carrier for delivery, but there are certain limitations faced by liposomes such as poor stability during storage [19]. Encapsulation and drug release profile may change during the storage of formulation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callMore From: Asian Journal of Pharmaceutical and Clinical Research
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
