Drug Design, Development and Therapy (Nov 2020)
Stoichiometrically Governed Curcumin Solid Dispersion and Its Cytotoxic Evaluation on Colorectal Adenocarcinoma Cells
Abstract
Jamal Moideen Muthu Mohamed,1 Ali Alqahtani,2 Fazil Ahmad,3 V Krishnaraju,2 K Kalpana4 1Department of Pharmaceutical Technology, BIT Campus, Anna University, Tiruchirappalli, Tamil Nadu 620024, India; 2Department of Pharmacology, College of Pharmacy, King Khalid University, Guraiger, Abha 62529, Saudi Arabia; 3Department of Anesthesia Technology, College of Applied Medical Sciences in Jubail, Imam Abdulrahman Bin Faisal University, Jubail, Saudi Arabia; 4Department of Pharmaceutical Analysis, Erode College of Pharmacy, Veppampalayam, Erode, Tamil Nadu 638112, IndiaCorrespondence: Jamal Moideen Muthu MohamedBIT Campus, Anna University, Tiruchirappalli, Tamil Nadu 620024, IndiaTel +91-9080018534Fax +91 431-2407988Email [email protected]: 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.Keywords: curcumin, phase solubility, MTT assay, colorectal cancer, in silico interaction, dissolution comparison
