title: In vitro characterization of a liposomal formulation of celecoxib containing 1,2-distearoyl-sn-glycero-3-phosphocholine, cholesterol, and polyethylene glycol and its functional effects against colorectal cancer cell lines.
abstract: Nanosized liposomal drug delivery systems are well suited for selective drug delivery at tumor sites. Celecoxib (CLX) is a highly hydrophobic cyclooxygenase-2 inhibitor that can reduce the incidence of colorectal polyps; however, the adverse cardiovascular effects limit its applicability. Here, we report a liposomal formulation of CLX using 1,2-Distearoyl-sn-glycero-3-phosphocholine, cholesterol, and polyethylene glycol. Encapsulation efficiency of the drug was greater than 70%; the release was slow and sustained with only 12%-20% of CLX released in the first 12 h. Flow cytometry and confocal microscopy studies using the colon cancer cell lines HCT-116 and SW620 showed significantly higher cellular association and internalization of the liposomes after incubation for 6 h when compared with 30 min. The liposomes did not colocalize with transferrin, but had a punctuate appearance, indicating vesicular localization. Cell proliferation was inhibited by 95% and 78%, respectively, in SW620 and HT29 cells after incubation with 600 μM liposomal CLX for 72 h. Moreover, cellular motility, as shown by a scratch wound healing assay, was also significantly (p = 0.006) inhibited when SW620 cells were incubated with 400 μM liposomal CLX. This is the first report of the successful encapsulation of CLX in a long-circulating liposomal formulation that could be effective against colorectal cancer.
authors.affiliation: Department of Biotechnology, Middle East Technical University, Ankara, 06800, Turkey.
authors.forename: Asli
authors.initials: A
authors.lastname: Erdoğ
authors.forename: Yanuar Dwi
authors.initials: YD
authors.lastname: Putra Limasale
authors.forename: Dilek
authors.initials: D
authors.lastname: Keskin
authors.forename: Ayşen
authors.initials: A
authors.lastname: Tezcaner
authors.forename: Sreeparna
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002784:Cholesterol / Q000737:chemistry*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000379:methods; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D008081:Liposomes; D010713:Phosphatidylcholines; D011720:Pyrazoles; D013449:Sulfonamides; D011092:Polyethylene Glycols; D002784:Cholesterol; C010942:1,2-distearoyllecithin; D000068579:Celecoxib
keywords: cancer; celecoxib; colon; drug delivery systems; liposome; nanoparticles; pegylation