Design of colloidal drug carriers of celecoxib for use in treatment of breast cancer and leukemia

• Published in: Materials Science & Engineering C Vol. 103; p. 109874
• Main Authors: Üner, Melike, Yener, Gülgün, Ergüven, Mine
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2019; Elsevier BV
• Subjects: Acute promyelocytic leukemia; Acute promyeloid leukemia; Apoptosis; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Calorimetry; Cancer therapy; Celecoxib; Celecoxib - chemistry; Celecoxib - pharmacokinetics; Celecoxib - pharmacology; Cell activation; Cell culture; Cell death; Colloids; COX-2 inhibitors; Cyclooxygenase-2; Differential scanning calorimetry; Drug carriers; Drug Carriers - chemistry; Drug Carriers - pharmacokinetics; Drug Carriers - pharmacology; Drug delivery; Drug delivery systems; Drug development; Electron micrographs; Emulsions; Female; High pressure; HL-60 Cells; Humans; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Lipids; Materials science; MCF-7 Cells; Morphology; Nanoemulsions; Nanoparticles; Nanostructured lipid carriers; Photon correlation spectroscopy; Promyeloid leukemia; Size distribution; Solid lipid nanoparticles; Spectroscopy; Nanostructured lipid carriers; Acute promyelocytic leukemia; Cancer therapy; Nanoemulsions; Breast cancer; Celecoxib; Solid lipid nanoparticles
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2019.109874

Inflammation develops initiation and pathological process of cancer. Nanoscale drug carriers are required to be investigated for delivery of actives at cellular level for treatment of various cancer types. Solid lipid nanoparticles (CLX-SLN), nanostructured lipid carriers (CLX-NLC) and a nanoemulsion (CLX-NE) of celecoxib (CLX), a selective cyclooxygenase-2 inhibitor, were formulated for use in remedy of breast cancer and acute promyelocytic leukemia. The hot high pressure homogenization technique was employed to product formulations. Scanning electron micrographs were utilized for morphological characterization of formulations. Laser diffraction (LD), photon correlation spectroscopy (PCS) and differential scanning calorimetry (DSC) were used for examination of their physical stability by storing them at various temperatures. Drug release profiles of formulations were obtained. Their activity on cancer cells was investigated in the cell culture experiments. Stable formulations having homogenous size distribution were obtained below 200 nm with high drug payloads between 93.76% and 96.66%. Nanoparticles were ascertained to contribute controlled drug release. CLX-SLN induced the highest decrease in numbers of human breast cancer and human acute promyelocytic leukemia cells through the activation of the cell death cascades especially apoptosis in comparison to CLX-NLC, CLX-NE and the pure CLX application (p < 0.05). Nanoformulations of CLX optimized in this study were found to have various advantages expected from sophisticated drug delivery systems in order to achieve higher CLX efficiency at cellular level. Thus, they are able to be administered efficaciously alone and in combination therapies in remedy of breast cancer and acute promyelocytic leukemia. [Display omitted] •SLN, NLC and NE of celecoxib were optimized by high pressure homogenization for treatment of breast cancer and leukemia.•Stable formulations with particle/droplet size below 200 nm in average that is suitable for colloid transport accross the tumor epithelium and easier cellular uptake.•Sustained drug delivery.•SLN, NLC and NE decreases in numbers of MCF-7 and HL-60 cells via triggering the apoptosis.•SLN overcome the resistance via the highest effective inhibition of midkine for MCF-7 and HL-60 cell lines compared to NLC, NE and pure CLX.