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Abstract
Background: Efficacy of anticancer drug is limited due to non-selectivity and toxicities allied with the drug; therefore the heart of the present work is to formulate drug delivery systems targeted selectively towards cancer cells with minimal toxicity to normal cells.
Purpose: Targeted drug delivery system of doxorubicin (DOX)-loaded niosomes using synthesized N-lauryl glucosamine (NLG) as a targeting ligand.
Methods: NLG-anchored DOX niosomes were developed using ethanol injection method.
Results: Developed niosomes had particle size <150 nm and high entrapment efficiency ∼90%. In vivo pharmacokinetics exhibited long circulating nature of targeted niosomes with improved bioavailability, which significantly reduced CL and Vd than DOX solution and non-targeted niosomes (35 fold and 2.5 fold, respectively). Tissue-distribution study and enzymatic assays revealed higher concentration of DOX solution in heart while no toxicity to major organs with developed targeted niosomes was observed. Solid skin melanoma tumor model in mice manifested the commendable targeting potential of targeted niosomes with significant reduction in tumor volume and high % survival rate without drop in body weight in comparison with DOX solution and non-targeted niosomes of DOX.
Conclusion: The glucosamine-anchored DOX-loaded targeted niosomes showed its potential in cancer targeted drug therapy with reduced toxicity.
| Abbreviations | ||
| ALT | = | alanine transaminase |
| CL | = | clearance |
| CPK | = | creatinine phosphokinase |
| DOX | = | doxorubicin |
| EDC.HCL | = | ethyl carbidimide hydrochloride |
| GLUT | = | glucose transporter |
| GSH | = | glutathione S-transferase |
| LDH | = | lactate dehydrogenase |
| LHRH | = | luteinizing hormone-releasing hormone |
| MDA | = | malonaldehyde |
| NHS | = | N-hydroxy succinimide |
| NLG | = | N-lauryl glucosamine |
| NTAR DoxNio | = | non-targeted doxorubicin niosomes |
| PBS | = | phosphate buffer saline |
| RGD | = | argynyl glycyl aspartic acid |
| SGOT | = | serum glutamate oxaloacetate transaminase |
| SGPT | = | serum glutamate pyruvate transaminase |
| SOD | = | superoxide dismutase |
| TAR DoxNio | = | targeted doxorubicin niosomes |
| Vd | = | volume of distribution |
Acknowledgements
Authors are thankful to University Grant Commission, Govt. of India for financial assistance during the research work, All India Council for Technical Education (AICTE-NAFETIC) for research facilities provided and Advanced Center for Treatment Research and Education in Cancer (ACTREC) for performing animal study.
Disclosure statement
Authors do not have conflicts of interest.