Efficacy of aerosolized celecoxib encapsulated nanostructured lipid carrier in non-small cell lung cancer in combination with docetaxel.
OBJECTIVE
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 ± 20 nm, 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.


CONCLUSIONS
Combination therapy with Cxb-NLC and Doc showed significant reduction in tumor growth which was further confirmed by proteomic analysis.
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University,, Tallahassee, Florida 32307, USA.
Apurva R
AR
Patel
Mahavir B
MB
Chougule
Townley
T
I
Ram
R
Patlolla
Guangdi
G
Wang
Mandip
M
Singh
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000068579:Celecoxib; D045744:Cell Line, Tumor; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000077143:Docetaxel; D004337:Drug Carriers / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D043823:Taxoids / Q000008:administration & dosage / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D008055:Lipids; D011720:Pyrazoles; D013449:Sulfonamides; D043823:Taxoids; D000077143:Docetaxel; D000068579:Celecoxib