This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Background
Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women. Curcumin (CMN) is obtained from a natural source and has no toxicity, even at high doses (8,000 mg/kg body weight in 24 hours) and was determined to have anticancer potency on several kinds of carcinoma. However, its medical applications were limited because of its low solubility and poor bioavailability.
Materials and Methods
To improve the medical applications of CMN, various hydrophilic carriers such as poloxamer 407 (PMX-407), poloxamer 188 (PMX-188), Gelucire 50/13 (Gel-50/13), and mannitol (MNL) were used to prepare a binary complex solid dispersion (SD). These binary SDs were characterized for aqueous solubility in various solvents. Physical stability, thermal behaviors, and morphology were determined by Fourier transform infrared spectrophotometric analysis, powder X-ray diffraction analysis, thermogravimetric analysis, differential scanning calorimetric analysis, scanning electron microscopy, dynamic light scattering study, and the novel dyeing test. In vitro drug release was determined by dissolution study. Based on the characterization, the better SD complex was optimized using Box-Behnken design (BBD). The cytotoxicity and apoptosis study of prepared CMN (C-SD) were used to test for colorectal adenocarcinoma cell lines.
Results
These results showed that the solubility of CMN is greatly improved after complexation with PXM-407 in SD. CMN is practically insoluble in water at acidic and neutral pH; however, the SD of CMN with PXM-407 produced significant improvement in solubility (1.266±0.0242 mg/mL) and dissolution (91.36±0.431% at 30 minutes); similarly, these data fit with a phase solubility study and in silico molecular modeling. Moreover, the solid-state characterization revealed that the SD complex exhibits the intermolecular hydrogen bond with drug and carrier. Also, the complex does not undergo any chemical modification owing to the amorphous form, and the dye test showed better coloring impact indicating the solubility of CMN. The cell cycle arrest confirmed at G2/M phase from flow cytometry analysis, and Western blot investigation was recognized molecular level cell death and the complex induced more exploit DNA during apoptosis.
Conclusion
This study confirmed that the ideal stoichiometric ratio of CMN with carrier to enhance its solubility was 1:1. This molecular complex of PXM-407 was found to be more effective against colorectal cancer (CRC) than pure CMN.
Green synthesis of silver nanoparticles (AgNPs) was synthesized from fresh garlic extract coupled with isoniazid hydrazide (INH), a commonly used antibiotic to treat tuberculosis. A molecular docking study conducted with the selected compounds compared with anthranilate phosphoribosyltransferase (trpD) from Mycobacterium tuberculosis. The aqueous extract of garlic was prepared and mixed with silver nitrate (AgNO3) solution for the superfast synthesis of stable AgNPs. INH was then conjugated with AgNPs at different ratios (v/v) to obtain stable INH-AgNPs conjugates (AgNCs). The resulting AgNCs characterized by FTIR spectra revealed the ultrafast formation of AgNPs (<5 s) and perfectly conjugated with INH. The shifting of λmax to longer wavelength, as found from UV spectral analysis, confirmed the formation of AgNCs, among which ideal formulations (F7, F10, and F13) have been pre-selected. The zeta particle size (PS) and the zeta potential (ZP) of AgNPs were found to be 145.3 ± 2.1 nm and −33.1 mV, respectively. These data were significantly different compared to that of AgNCs (160 ± 2.7 nm and −14.4 mV for F7; 208.9 ± 2.9 nm and −19.8 mV for F10; and 281.3 ± 3.6 nm and −19.5 mV for F13), most probably due to INH conjugation. The results of XRD, SEM and EDX confirmed the formation of AgNCs. From UV spectral analysis, EE of INH as 51.6 ± 5.21, 53.6 ± 6.88, and 70.01 ± 7.11 %, for F7, F10, and F13, respectively. The stability of the three formulations was confirmed in various physiological conditions. Drug was released in a sustainable fashion. Besides, from the preferred 23 compounds, five compounds namely Sativoside R2, Degalactotigonin, Proto-desgalactotigonin, Eruboside B and Sativoside R1 showed a better docking score than trpD, and therefore may help in promoting anti-tubercular activity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.