Efficacy of Aerosolized Celecoxib Encapsulated Nanostructured Lipid Carrier in Non-small Cell Lung Cancer in Combination with Docetaxel

Abstract

Purpose Evaluation of in-vivo anticancer activity of aerosolized Celecoxib encapsulated Nanolipidcarriers (Cxb-NLC) as a single therapeutic agent and combined with intravenously administered Docetaxel (Doc) against non-small cell lung cancer. Methods Cxb-NLC were prepared by high-pressure homogenization and were characterized for its physicochemical characteristics. Metastatic A549 tumor model in Nu/Nu mice was used to evaluate response of aerosolized Cxb-NLC & Doc. Isolated lung tumor samples were analyzed for: a) DNA fragmentation and cleaved caspase-3 by immunohistochemistry, b) apoptotic and angiogenic protein markers by western blot, c) global proteomic alterations by an isobaric labeling quantitative proteomic method and d) toxicity studies of NLC. Results The particle size of Cxb-NLC was 217±20nm, while entrapment efficiency was more than 90%. Cxb-NLC and Doc alone and in combination showed 25±4 %, 37±5 %, and 67±4 % reduction in tumor size respectively compared to control. Proteomic analysis with combination treatment further revealed significantly decreased expression of multiple pro-survival and pro-metastasis proteins as well as tumor invasion markers and the expression of S100 family proteins, such as S100A6 and S100P were decreased by 2.5 and 1.6 fold. Conclusion Combination therapy with Cxb-NLC and Doc showed significant reduction in tumor growth which was further confirmed by proteomic analysis.

EphA2 Targeting Pegylated Nanocarrier Drug Delivery System for Treatment of Lung Cancer

“…7). Also, we analyzed wet to dry lung weight ratio (WDR) as to measure the lung edema (33). The WDR of 5.63±0.71 and 5.20±0.35 was found in the tumor bearing mice treated with ENDDs and NDDs.…”

“…Nano-lipid carriers (NCs) were prepared by modified hot melt homogenization (33) using triglycerides and optimized process variables. Briefly, DIM-P and Doc were dispersed in organic solvent.…”

“…The Nicomp 380 ZLS (Particle Sizing Systems, Port Richey, FL) was used to measure particle size and zeta potential of NDs or ENDDs. The drug loading and entrapment efficiency were determined as reported earlier (33). …”

“…To evaluate in-vivo anticancer activity of ENDDs, orthotopic A549 cell tumor model (5) was developed as reported earlier and H1650 cells were injected via tail vein to develop the metastatic tumor model (33). Ten days after tumor implantation, mice were randomly divided into the following groups ( n =10) to receive various DIM-P and Doc formulations; A) control group received vehicle (placebo ENDDs); B) NDi (DIM-P equivalent of 5 mg/kg) every fifth day; C) NDo (Doc equivalent of 2 mg/kg) every fifth day; D) NDDs (DIM-P equivalent of 5 mg/kg and Doc equivalent of 2 mg/kg) every fifth day; E) ENDDs (DIM-P equivalent of 5 mg/kg and Doc equivalent of 2 mg/kg) every fifth day.…”

Silencing of COX-2 by RNAi Modulates Epithelial-Mesenchymal Transition in Breast Cancer Cells Partially Dependent on the PGE2Cascade

“…Recently, data have showed that selective COX-2 inhibitors, such as celecoxib have antiancer effects (Sooriakumaran et al, 2009;Patel et al, 2013), treatment with celecoxib maximally affected growth of MDA-MB-231 cells (Bocca et al, 2011); RNAi targeting for COX-2 was also used to block the growth of breast cancer cells. In this study, we tested the ability of celecoxib on EMT modulation; results show that celecoxib could change the cell appearance to epithelial state slightly.…”