Preparation, Characterization And Anti-cancer Screening Of Pectin Coated PTX-Chitosan Nano-Lipid-Construct For Management Of Liver Cancer.
Keywords:
Liver cancer, Nano lipid particles, Paclitaxel, Ex-vivo study, Zeta potential measurement, Electron microscopy
Abstract
Hepatocellular carcinoma is the most common type of primary liver cancer. Liver cancer happens when liver cells develop mutations in their DNA. Paclitaxel is a natural diterpenoid compound with antitumor activity. The main objective of study was to preparation, characterization and anticancer screening of pectin coated Paclitaxel-chitosan nano-lipid-construct for the management of liver cancer. In this study, we performed physicochemical characterization of the drug and pre-formulations study, and prepared and optimized pectin coated nano lipid formulation. Nano lipid particles were characterized by size and shape, scanning electron microscopy, particle size distribution, Zeta potential measurement, entrapment efficiency and ex-vivo study in HeLa cells. The pectin coated PTX-chitosan NLCs (P-PCNLCs) has successfully prepared by Ion gelation method and characterized for the particle size, zeta-potential, polydispersity index and surface morphology. The P-PCNLCs having the particle size 180.9±.12 nm that is suitable for the active targeting towards the cancer sites as well as for the engulfment by the carrier protein present in cell surface. The entrapment efficiency of the particle was 86.23±0.32%. The ex-vivo study data are in agreement with strategies that active targeting provides the promising result of cure and treatment of cancerous cell. The cytotoxicity of P-PCNLCs was significantly increased compared to PTX. Nano-lipid-construct exhibited a remarkably higher uptake in the HeLa cells compared to that of free drug (PTX).The nanoscale effect and targeting effect of P-PCNLCs could increase the drug accumulation in tumor cells, which leads to high drug concentrations in tumor cells and strongly inhibiting cell proliferation.
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2. Ang SF, Ng ES, Li H, Ong YH, Choo SP, Ngeow J, Toh HC, Lim KH, Yap HY, Tan CK, Ooi LL. The Singapore Liver Cancer Recurrence (SLICER) Score for relapse prediction in patients with surgically resected hepatocellular carcinoma. PloS one 2015 ;10(4):e0118658.
3. Ang SF, Ng ES, Li H, Ong YH, Choo SP, Ngeow J, Toh HC, Lim KH, Yap HY, Tan CK, Ooi LL. The Singapore Liver Cancer Recurrence (SLICER) Score for relapse prediction in patients with surgically resected hepatocellular carcinoma. PloS one 2015 ;10(4):e0118658.
4. Breiner KM, Schaller H, Knolle PA. Endothelial cell–mediated uptake of a hepatitis B virus: a new concept of liver targeting of hepatotropic microorganisms. Hepatology 2001;34(4):803-8.
5. Cheng AL, Kang YK, Chen Z, Tsao CJ, Qin S, Kim JS, Luo R, Feng J, Ye S, Yang TS, Xu J. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. The lancet Oncology 2009 ;10(1):25-34.
6. Chochi Y, Kawauchi S, Nakao M, Furuya T, Hashimoto K, Oga A, Oka M, Sasaki K. A copy number gain of the 6p arm is linked with advanced hepatocellular carcinoma: an array‐based comparative genomic hybridization study. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland 2009 ;217(5):677-84.
7. Curtin JP, Blessing JA, Webster KD, Rose PG, Mayer AR, Fowler WC, Jr, Malfetano JH, Alvarez RD. Paclitaxel, an active agent in non-squamous carcinomas of the uterine cervix: A Gynecologic Oncology Group study. Journal of Clinical Oncology 2001; 19: 1275-1278.
8. Fan J, Yang GS, Fu ZR, Peng ZH, Xia Q, Peng CH, Qian JM, Zhou J, Xu Y, Qiu SJ, Zhong L. Liver transplantation outcomes in 1,078 hepatocellular carcinoma patients: a multi-center experience in Shanghai, China. Journal of cancer research and clinical oncology 2009; 135(10):1403-12.
9. Farazi PA, DePinho RA. Hepatocellular carcinoma pathogenesis: From genes to environment. Nature Reviews Cancer 2006; 6: 674–687.
10. Heidelbaugh JJ, Bruderly M. Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation. American family physician 2006 ;74(5).
11. Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology 2018 ;67(1):358-80.
12. Kumar SS, Saha AK, Kavitha K, Basu SK. Evaluation of clobazam loaded ionically cross-linked microspheres using chitosan. Der Pharmacia Sinica. 2012;3(6):616-23
13. Lan M, Zhu L, Wang Y. Multifunctional nanobubbles carrying indocyanine green and paclitaxel for molecular imaging and the treatment of prostate cancer. J Nanobiotechnology 2020; 18: 121-125.
14. Li S, Wei J, Yuan L, et al. RGD-modified endostatin peptide 530 derived from endostatin suppresses invasion and migration of HepG2 cells through the αvβ3 pathway. CancerBiotherRadio-pharmaceutics 2011; 26: 529–538.
15. Liang HF, Chen CT, Chen SC, Kulkarni AR, Chiu YL, Chen MC, Sung HW. Paclitaxel-loaded poly (γ-glutamic acid)-poly (lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials 2006;27(9):2051-2059.
16. Liang HF, Chen CT, Chen SC, Kulkarni AR, Chiu YL, Chen MC, Sung HW. Paclitaxel-loaded poly (γ-glutamic acid)-poly (lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials 2006;27(9):2051-9.
17. Liu X, Wang W, Wang Z. Recent progress in understanding the effects of autophagy in hepatocellular carcinoma. Chinese Journal of Hepatobiliary Surgery2014; 20: 69–73.
18. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc JF, De Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M. Sorafenib in advanced hepatocellular carcinoma. New England journal of medicine 2008 ;359(4):378-90.
19. Ma KW, Cheung TT. Surgical resection of localized hepatocellular carcinoma: patient selection and special consideration. Journal of hepatocellular carcinoma 2017;4:1
20. Madoff DC, Hicks ME, Vauthey JN, Charnsangavej C, Morello Jr FA, Ahrar K, Wallace MJ, Gupta S. Transhepatic portal vein embolization: anatomy, indications, and technical considerations. Radiographics 2002 (5):1063-76..
21. Mahajan H, Gattani S, Surana S. Spray dried mucoadhesive microspheres of ondansetron for nasal administration. International journal of pharmaceutical sciences and nanotechnology 2008;(3):267-74.
22. McGuire WP, Blessing JA, Moore D, Lentz SS, Photopulos G. Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. Journal of Clinical Oncology 1996; 14: 792–795.
23. Pan Y, Ye S, Yuan D. Hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) pathway contributes to the proliferation of hepatoma cells. MutationResearch 2014;763–764:10–18.
24. Patel NR, Patel DA, Bharadia PD, Pandya V, Modi D. Microsphere as a novel drug delivery. International Journal of Pharmacy & Life Sciences 2011;2(8).
25. Pawlik TM, Abdalla EK, Vauthey JN. Liver transplantation for hepatocellular carcinoma: need for a new patient selection strategy. Annals of surgery 2004 ;240(5):923
26. Prasanth VV, Moy AC, Mathew ST, Mathapan R. Microspheres-an overview. International journal of research in pharmaceutical and biomedical sciences 2011(2):332-8.
27. Qin Wang, Ying-Tzu Yen, Chen Xie, Fangcen Liu, Qin Liu, Jia Wei, Lixia Yu, Lifeng Wang, Fanyan Meng, Rutian Li, Baorui Liu. (2021) Combined delivery of salinomycin and docetaxel by dual-targeting gelatinase nanoparticles effectively inhibits cervical cancer cells and cancer stem cells. Drug Delivery 28:1, pages 510-519.
28. Rajasekaran D, Srivastava J, Ebeid K, Gredler R, Akiel M, Jariwala N, Robertson CL, Shen XN, Siddiq A, Fisher PB, Salem AK. Combination of nanoparticle-delivered siRNA for astrocyte elevated gene-1 (AEG-1) and all-trans retinoic acid (ATRA): an effective therapeutic strategy for hepatocellular carcinoma (HCC). Bioconjugate chemistry 2015; (8):1651-61.
29. Rose PG, Blessing JA, Gershenson DM, McGehee R. Paclitaxel and cisplatin as first-line therapy in recurrent or advanced squamous cell carcinoma of the cervix: A gynecologic oncology group study. J Clin Oncol. 1999; 17: 2676–2680
30. Sachan NK, Singh B, Rao KR. Controlled drug delivery through microencapsulation. Malaysian Journal of Pharmaceutical Sciences 2006;4(1):65-81.
31. Shibata T, Aburatani H. Exploration of liver cancer genomes. Nature reviews Gastroenterology & hepatology 2014(6):340.
32. Smedsrød B, Pertoft H, Eggertsen G, Sundström C. Functional and morphological characterization of cultures of Kupffer cells and liver endothelial cells prepared by means of density separation in Percoll, and selective substrate adherence. Cell and tissue Research 1985;241(3):639-49.
33. Sunitha S, Amareshwar P, Santhosh Kumar M, Chakravarti P. Preparation and evaluation of tramadol hydrochloride microspheres by coacervation phase separation technique using various solvents and non-solvents. Journal of Global Pharmaceutical Technology 2011(4):33-41.
34. Thakur R, Anwer MK, Shams MS, Ali A, Khar RK, Shakeel F, Taha EI. Proniosomal transdermal therapeutic system of losartan potassium: development and pharmacokinetic evaluation. Journal of drug targeting 2009;17(6):442-9.
35. Vasir JK, Tambwekar K, Garg S. Bioadhesive microspheres as a controlled drug delivery system. International journal of Pharmaceutics 2003;255(1-2):13-32.
36. Yang C, Merlin D. Lipid-Based Drug Delivery Nanoplatforms for Colorectal Cancer Therapy.Nanomaterials 2020; 10: 1424-28.
37. Zhang C, He H, Zhang H, et al. The blockage of Ras/ERK pathway augments the sensitivity of SphK1 inhibitor SKI II in human hepatoma HepG2 cells. Biochemical and BiophysicalResearchandCommunication 2013; 434: 35–41.
38. Zhao MD, Li JQ, Chen FY, Dong W, Wen LJ, Fei WD, Zhang X, Yang PL, Zhang XM, Zheng CH. Co-Delivery of Curcumin and Paclitaxel by “Core-Shell” Targeting Amphiphilic Copolymer to Reverse Resistance in the Treatment of Ovarian Cancer. International Journal of Nanomedicine 2019; 14: 9453.
Published
2024-09-10
How to Cite
Manish Mahobiya, Dr. Arun Patel, & Dr. Naveen Shivavedi. (2024). Preparation, Characterization And Anti-cancer Screening Of Pectin Coated PTX-Chitosan Nano-Lipid-Construct For Management Of Liver Cancer. Revista Electronica De Veterinaria, 25(1S), 757-766. Retrieved from https://veterinaria.org/index.php/REDVET/article/view/852
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