DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20204488

Targeted nano-sized drug design in cancer treatments: development of new nano-sized formulations for the use of anti-cancerogenic lisinopril in the treatment of colorectal cancer

Emre Avci, Aslı Kara, Gamze Catagay, Gulcin Alp Avci

Abstract


Background: Colorectal cancer emerges as a serious health problem all over the world and results in approximately 700,000 deaths every year. Therefore, studies are carried out to develop alternative treatment methods to reduce the side effects of anticancer drugs in cancer treatment. Targeted nanoparticle therapies are tried to be developed especially with controlled drug release. Lisinopril, an angiotensin-converting enzyme inhibitor, is a widely used drug in the treatment of hypertension and has been shown to have anticancer activity on various types of cancer.

Methods: This study, blank and 3 different amounts of lisinopril loaded nanoparticles were prepared by triblock poly (lactic acid)–poly (ethylene glycol)–poly (lactic acid) (PLA-PEG-PLA) block copolymer which is a biocompatible and biodegradable polymer by using water/oil/water emulsion method and then characterized. The viability of the blank formulations in murine fibroblast (L929) cells, which is the healthy cell line, was determined within the scope of biocompatibility studies.

Results: The anticarcinogenic activity of lisinopril drug, blank and lisinopril loaded nanoparticles was determined in caco-2 cells which are human epithelial colorectal adenocarcinoma cell line.

Conclusions: Lisinopril loaded nanoparticles were successfully prepared in this study. It is thought that increasing the amount of drug-loaded can be a promising approach to an alternative treatment method for the use of antihypertensive drugs in the treatment of colorectal cancer.


Keywords


Colorectal cancer, Antihypertensive drugs, Polymeric nanoparticle, Targeted drug design, Lisinopril

Full Text:

PDF

References


Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, et al. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87-108.

Abhishek B, Melissa W, Samir G. Colorectal cancer is a leading cause of cancer incidence and mortality among adults younger than 50 years in the USA: a SEER-based analysis with comparison to other young-onset cancers. J Investig Med. 2017;65(2):311-5.

Mármol I, Sánchez-de-Diego C, Pradilla Dieste A, Cerrada E, Rodriguez Yoldi MJ. Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Inter J Mol Sci. 2017;18(1):197.

Behzad M, Ali M, Sadaf D, Solmaz S, Behzad B. Adv Pharm Bull. The Different Mechanisms of Cancer Drug Resistance: A Brief Review. 2017;7(3):339-48.

Latha GS, Prasad SBC, Rao R. In vitro anti-cancer activities of few antihypertensive agents against carcinoma of scalp by MTT assay. J Chem Bio Phy Sci. 2011;1(2):299-303.

Sharkawi FZE, Shemy HAE, Khaled H. Anticancer activity of some commercial antihypertensive drugs by Neutral Red assay. Life Sci J. 2013;10(1):609-13.

Raia JJ, Barone JA, Byerly WG, Lacy CR. Angiotensin-converting enzyme inhibitors: a comparative review. DICP. 1990;24(5):506-25.

Munro MJ, Wickremesekera AC, Davis PF, Marsh R, Tan ST, et al. Renin-angiotensin system and cancer: A review. Integr Cancer Sci Therap. 2017;4.

Aniket G, Janel K, Brandon P, Prakash R. Targeting Cancer using Polymeric Nanoparticle mediated Combination Chemotherapy. Int J Nanomed Nanosurg. 2016;2(3):10.

Shin HC, Alani AW, Cho H, Bae Y, Kolesar JM,et al. A 3-in-1 polymeric micelle nanocontainer for poorly water-soluble drugs. Mol Pharm. 2011;8(4):1257-65.

Honary S, Zahir F. Effect of Zeta Potential on the Properties of Nano-Drug Delivery Systems - A Review (Part 2) Tropical J Pharm Res. 2013;12:265-73.

Danafar H, Rostamizadeg, Davaran S, Hamidi M. PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril. Drug Dev Ind Pharm. 2014;40(10):1411-20.

Chander V, Mohan M, Seth R, Singh P, Singh R, Gupta S. Development and Validation of RP-HPLC Method for the Estimation of Lisinopril in Tablet Dosage Form. Anal Chem Lett. 2012;2(5):309-13.

Andima M, Costabile G , Isert L , Ndakala AJ, Derese S, Merkel OM. Evaluation of β-Sitosterol Loaded PLGA and PEG-PLA Nanoparticles for Effective Treatment of Breast Cancer: Preparation, Physicochemical Characterization, and Antitumor Activity. Pharmaceutics. 2018;10(232):1-18.

Makar GA, Holmes JH, Yang YX. Angiotensin-converting enzyme inhibitor therapy and colorectal cancer risk. J Natl Cancer Inst. 2014;106(2):374.

Babu AP, Swarna Latha G, Bhavani Charan Prasad S, Ramachandra Rao CSV. In Vitrocancer activities of few anti-hypertensive agents against carcinoma of cervix by MTT assay. J Pharm Res Rev. 2011;1:1-3.

Shen S, Wu Y, Liu Y, Wu D. High drug-loading nanomedicines: progress, current status, and prospects. Int J Nanomedicine. 2017;12:4085-109.

Cai K, He X, Song Z, Yin Q, Zhang Y, Uckun FM, Jiang C, Cheng J. Dimeric drug polymeric nanoparticles with exceptionally high drug loading and quantitative loading efficiency. J Am Chem Soc. 2015;137(10):3458-61.

Grenha A, Grainger CI, Dailey LA, Seijo B, Martin GP, Remuñán-López C, Forbes B. Chitosan nanoparticles are compatible with respiratory epithelial cells in vitro. Eur J Pharm Sci. 2007;31(2):73-84.

Derman S, Mustafaeva AZ, Canim AS, Mansuroglu B., Kizilbey K, et al. The Study Of Synthetic Peptide Loaded PLGA Nanoparticles Cytotoxicity In Vitro. Fresenius Environ Bull. 2017;26(2a):1646-53.

Vijayakumar S, Ganesan S. In vitro cytotoxicity assay on gold nanoparticles with different stabilizing agents. J Nano. 2012;14.

Abid NBS, Rouis Z, Nefzi F, Souelah N. Aouni M. Evaluation of dimethylthiazol diphenyl tetrazolium bromide and propidium iodide inclusion assays for the evaluation of cell viability by flow cytometry. J Appl Pharm Sci. 2012;2:10-4.