SYNTHESIS AND OPTIMIZATION OF GEMCITABINE-LOADED MIL-101NH2 (Fe) NANOCARRIERS: RESPONSE SURFACE METHODOLOGY APPROACH

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.

Optimization of Supercritical CO2 Natural Dye Extraction from Brown Seaweed (Sargassum Sp.) via Response Surface Methodology

This paper discusses the effects of two main parameters (pressure and temperature) in supercritical carbon dioxideextraction of Sargassum sp. through response surface methodology (RSM). Perturbation plot shown significant effects of all process parameters on the yield of extract. An experimental design software was designated to achieve optimization on the process situations pertaining maximum extraction yield. The optimal conditions perceived were at pressure of 4500 psi and temperature of 65°C. The highest yield of extract achieved was 2.7 mg-extract/g-dried sample under the optimum conditions. The yield of extract was then further analysed via Gas Chromatography Mass Spectrometry (GCMS) and it was found that Sargassum sp. contains sterols, pentadecanoic acid, 14-methyl ester, 9-Hexadecenoic acid, methyl ester and phytol which are the constituents of bioactive compounds and antimicrobial properties.

Optimization of Cholesterol Removal by Probiotics in the Presence of Prebiotics by Using a Response Surface Method

ABSTRACT Lactobacillus casei ASCC 292 was grown in the presence of six prebiotics, namely, sorbitol, mannitol, maltodextrin, high-amylose maize, fructooligosaccharide (FOS), and inulin, in order to determine the combination of probiotic and prebiotics that would remove the highest level of cholesterol. A first-order model showed that the combination of L. casei ASCC 292, FOS, and maltodextrin was the most efficient for the removal of cholesterol, and the optimum experimental region was developed by using the steepest ascent. This led to the middle points of probiotic (1.70% [wt/vol]), FOS (4.80% [wt/vol]), and maltodextrin (6.80% [wt/vol]) for the development of a central composite design for optimization. Perturbation plot, response surface, and coefficient estimates showed that all three factors had significant quadratic effects on cholesterol removal, with FOS showing the most conspicuous quadratic change. A second-order polynomial regression model estimated that the optimum condition of the factors for cholesterol removal by L. casei ASCC 292 is 1.71% (wt/vol) probiotic, 4.95% (wt/vol) FOS, and 6.62% (wt/vol) maltodextrin. Validation experiments showed that the predicted optimum conditions were more efficient than the high and low levels of the factors and the center points. A response surface method proved reliable for developing the model, optimizing factors, and analyzing interaction effects. Analyses of growth, substrate utilization, growth yield, mean doubling time, and short-chain fatty acid (SCFA) production by the use of quadratic models indicated that cholesterol removal was growth associated. The concentration of L. casei ASCC 292 had the most significant quadratic effect on all responses studied, except for substrate utilization and SCFA production, which were significantly (P < 0.05) influenced by the interactions between the probiotic and both prebiotics, indicating that they were closely associated with the uptake of prebiotics.