Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model.
Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC50value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p < 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P < 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation.
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India.
Malti
M
Arya
Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research , Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, U.P., India.
Prakash
P
Tiwari
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India.
Chandra Bhushan
CB
Tripathi
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India.
Poonam
P
Parashar
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India.
Mahendra
M
Singh
CSIR-Central Institute of Medicinal and Aromatic Plants , PO CIMAP, Lucknow-226015, U. P., India.
Priyam
P
Sinha
CSIR-Central Institute of Medicinal and Aromatic Plants , PO CIMAP, Lucknow-226015, U. P., India.
Narayan P
NP
Yadav
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India.
Gaurav
G
Kaithwas
Environmental Carcinogenesis Division, CSIR-Indian Institute of Toxicology Research , Post Box No. 80, Mahatma Gandhi Marg, Lucknow-226001, U.P., India.
Krishna P
KP
Gupta
Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University , Vidya Vihar, Raebareli Road, Lucknow-226025, U.P., India.
Shubhini A
0000-0002-4180-0931
SA
Saraf
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000188:drug therapy*; D051379:Mice; D010833:Phytic Acid / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018809:Proliferating Cell Nuclear Antigen; D019938:Cyclin D1; D015127:9,10-Dimethyl-1,2-benzanthracene; D010833:Phytic Acid; D051546:Cyclooxygenase 2
RT-PCR; SK-MEL-2 cell line; Western blotting; histopathology; niosomes; phytic acid; skin cancer; suspension