5-Fluorouracil Loaded Orally Administered WGA-decorated Poly(lacticco- glycolic Acid) Nanoparticles for Treatment of Colorectal Cancer: In Vivo Evaluation

Author(s): Aditya N. Pandey, Kuldeep Rajpoot, Sunil K. Jain*

Journal Name: Current Nanomedicine
(Formerly Recent Patents on Nanomedicine)

Volume 11 , Issue 1 , 2021


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Graphical Abstract:


Abstract:

Background: Several studies have suggested the potential aptitude of polylactic-co-glycolic acid (PLGA)-derived nanoparticles (NPs) to improve the antitumor efficacy of anticancer drugs against colon cancer. Further, conjugation of lectins over the surface of the NPs may ameliorate interaction and thus enhance the attachment of NPs with receptors.

Objective: The main goal of the study was to prepare and evaluate the targeting potential (in vivo) of the optimized NPs against colorectal cancer.

Methods: The 5-fluorouracil (5-FU) loaded and wheat germ agglutinin (WGA)-conjugated PLGA- NPs (WFUNPs) were prepared and then they were evaluated in vivo for targeting aptitude of formulation using gamma scintigraphy after oral delivery. The WGA-conjugated and non-conjugated optimized NPs were compared for any significant results. Further, optimized formulations were also assessed for different parameters such as radiolabeling efficiency, sodium pertechnetate uptake, stability of NPs, and organ distribution study.

Results: Findings suggested prolonged retention of 99mTc-tagged WFUNPs in the colonic region after 24 h study. Eventually, the outcome from conjugated formulation revealed enhanced bioavailability of the drug in blood plasma for up to 24 h.

Conclusion: In conclusion, WGA-conjugation to NPs could improve the performance of the PLGA- NPs in the treatment of colorectal cancer.

Keywords: Colorectal cancer, 5-Fluorouracil, nanoparticles, poly(lactic-co-glycolic acid), Wheat germ agglutinin, Gamma- scintigraphy.

[1]
Patrey NK, Rajpoot K, Jain AK, Jain SK. Diltiazem loaded floating microspheres of Ethylcellulose and Eudragit for gastric delivery: in vitro evaluation. Asian J Biomat Res 2016; 2: 71-7.
[2]
Jain SK, Patel K, Rajpoot K, Jain A. Development of a Berberine Loaded Multifunctional Design for the Treatment of Helicobacter pylori Induced Gastric Ulcer. Drug Deliv Lett 2019; 9: 50-7.
[http://dx.doi.org/10.2174/2210303108666181120110756]
[3]
Rajpoot K, Jain SK. Colorectal cancer-targeted delivery of oxaliplatin via folic acid-grafted solid lipid nanoparticles: preparation, optimization, and in vitro evaluation. Artif Cells Nanomed Biotechnol 2018; 46(6): 1236-47.
[http://dx.doi.org/10.1080/21691401.2017.1366338] [PMID: 28849671]
[4]
Rajpoot K. Solid Lipid Nanoparticles: A Promising Nanomaterial in Drug Delivery. Curr Pharm Des 2019; 25(37): 3943-59.
[http://dx.doi.org/10.2174/1381612825666190903155321] [PMID: 31481000]
[5]
Rajpoot K, Jain SK. Irinotecan hydrochloride trihydrate loaded folic acid-tailored solid lipid nanoparticles for targeting colorectal cancer: development, characterization, and in vitro cytotoxicity study using HT-29 cells. J Microencapsul 2019; 36(7): 659-76.
[http://dx.doi.org/10.1080/02652048.2019.1665723] [PMID: 31495238]
[6]
Jain SK, Kumar A, Kumar A, Pandey AN, Rajpoot K. Development and in vitro characterization of a multiparticulate delivery system for acyclovir-resinate complex. Artif Cells Nanomed Biotechnol 2016; 44(5): 1266-75.
[http://dx.doi.org/10.3109/21691401.2015.1024841] [PMID: 25813568]
[7]
Jain SK, Prajapati N, Rajpoot K, Kumar A. A novel sustained release drug-resin complex-based microbeads of ciprofloxacin HCl. Artif Cells Nanomed Biotechnol 2016; 44(8): 1891-900.
[http://dx.doi.org/10.3109/21691401.2015.1111233] [PMID: 26698089]
[8]
Rajpoot K, Jain SK. Oral delivery of pH-responsive alginate microbeads incorporating folic acid-grafted solid lipid nanoparticles exhibits enhanced targeting effect against colorectal cancer: A dual-targeted approach. Int J Biol Macromol 2020; 151: 830-44.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.132] [PMID: 32061847]
[9]
Uhl P, Pantze S, Storck P, et al. Oral delivery of vancomycin by tetraether lipid liposomes. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 2017; 108: 111-8.
[http://dx.doi.org/10.1016/j.ejps.2017.07.013]
[10]
Minko T. Drug targeting to the colon with lectins and neoglycoconjugates. Adv Drug Deliv Rev 2004; 56(4): 491-509.
[http://dx.doi.org/10.1016/j.addr.2003.10.017] [PMID: 14969755]
[11]
Tang Q, Wang Y, Huang R, et al. Preparation of anti-tumor nanoparticle and its inhibition to peritoneal dissemination of colon cancer. PLoS One 2014; 9(6): e98455.
[http://dx.doi.org/10.1371/journal.pone.0098455] [PMID: 24896096]
[12]
Malet-Martino M, Martino R. Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT, S-1): a review. Oncologist 2002; 7(4): 288-323.
[http://dx.doi.org/10.1634/theoncologist.7-4-288] [PMID: 12185293]
[13]
Shakeel F, Haq N, Al-Dhfyan A, Alanazi FK, Alsarra IA. Chemoprevention of skin cancer using low HLB surfactant nanoemulsion of 5-fluorouracil: a preliminary study. Drug Deliv 2015; 22(4): 573-80.
[http://dx.doi.org/10.3109/10717544.2013.868557] [PMID: 24350612]
[14]
van Kuilenburg AB, Maring JG. Evaluation of 5-fluorouracil pharmacokinetic models and therapeutic drug monitoring in cancer patients. Pharmacogenomics 2013; 14(7): 799-811.
[http://dx.doi.org/10.2217/pgs.13.54] [PMID: 23651027]
[15]
Shakeri-Zadeh A, Khoee S, Shiran M-B, Sharifi AM, Khoei S. Synergistic effects of magnetic drug targeting using a newly developed nanocapsule and tumor irradiation by ultrasound on CT26 tumors in BALB/c mice. J Mater Chem B Mater Biol Med 2015; 3(9): 1879-87.
[http://dx.doi.org/10.1039/C4TB01708K] [PMID: 32262260]
[16]
Wang Y, Li P, Chen L, Gao W, Zeng F, Kong LX. Targeted delivery of 5-fluorouracil to HT-29 cells using high efficient folic acid-conjugated nanoparticles. Drug Deliv 2015; 22(2): 191-8.
[http://dx.doi.org/10.3109/10717544.2013.875603] [PMID: 24437926]
[17]
Badran MM, Mady MM, Ghannam MM, Shakeel F. Preparation and characterization of polymeric nanoparticles surface modified with chitosan for target treatment of colorectal cancer. Int J Biol Macromol 2017; 95: 643-9.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.11.098] [PMID: 27908720]
[18]
Pooja D, Kulhari H, Kuncha M, et al. Improving Efficacy, Oral Bioavailability, and Delivery of Paclitaxel Using Protein-Grafted Solid Lipid Nanoparticles. Mol Pharm 2016; 13(11): 3903-12.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00691] [PMID: 27696858]
[19]
Bies C, Lehr CM, Woodley JF. Lectin-mediated drug targeting: history and applications. Adv Drug Deliv Rev 2004; 56(4): 425-35.
[http://dx.doi.org/10.1016/j.addr.2003.10.030] [PMID: 14969751]
[20]
Clark MA, Hirst BH, Jepson MA. Lectin-mediated mucosal delivery of drugs and microparticles. Adv Drug Deliv Rev 2000; 43(2-3): 207-23.
[http://dx.doi.org/10.1016/S0169-409X(00)00070-3] [PMID: 10967227]
[21]
Gabor F, Schwarzbauer A, Wirth M. Lectin-mediated drug delivery: binding and uptake of BSA-WGA conjugates using the Caco-2 model. Int J Pharm 2002; 237(1-2): 227-39.
[http://dx.doi.org/10.1016/S0378-5173(02)00049-2] [PMID: 11955820]
[22]
Yin Y, Chen D, Qiao M, Lu Z, Hu H. Preparation and evaluation of lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin. J Control Release 2006; 116(3): 337-45.
[http://dx.doi.org/10.1016/j.jconrel.2006.09.015] [PMID: 17097180]
[23]
Zou W, Liu C, Chen Z, Zhang N. Studies on bioadhesive PLGA nanoparticles: A promising gene delivery system for efficient gene therapy to lung cancer. Int J Pharm 2009; 370(1-2): 187-95.
[http://dx.doi.org/10.1016/j.ijpharm.2008.11.016] [PMID: 19073241]
[24]
Olde Damink LHH, Dijkstra PJ, van Luyn MJA, van Wachem PB, Nieuwenhuis P, Feijen J. Cross-linking of dermal sheep collagen using a water-soluble carbodiimide. Biomaterials 1996; 17(8): 765-73.
[http://dx.doi.org/10.1016/0142-9612(96)81413-X] [PMID: 8730960]
[25]
Ponchel G, Irache J. Specific and non-specific bioadhesive particulate systems for oral delivery to the gastrointestinal tract. Adv Drug Deliv Rev 1998; 34(2-3): 191-219.
[http://dx.doi.org/10.1016/S0169-409X(98)00040-4] [PMID: 10837678]
[26]
Babbar AK, Singh AK, Goel HC, Chauhan UPS, Sharma RK. Evaluation of (99m)Tc-labeled photosan-3, a hematoporphyrin derivative, as a potential radiopharmaceutical for tumor scintigraphy. Nucl Med Biol 2000; 27(4): 419-26.
[http://dx.doi.org/10.1016/S0969-8051(00)00092-5] [PMID: 10938479]
[27]
Upadhyay KK, Bhatt AN, Castro E, et al. In vitro and in vivo evaluation of docetaxel loaded biodegradable polymersomes. Macromol Biosci 2010; 10(5): 503-12.
[http://dx.doi.org/10.1002/mabi.200900415] [PMID: 20232310]
[28]
Anande NM, Jain SK, Jain NK. Con-A conjugated mucoadhesive microspheres for the colonic delivery of diloxanide furoate. Int J Pharm 2008; 359(1-2): 182-9.
[http://dx.doi.org/10.1016/j.ijpharm.2008.04.009] [PMID: 18486369]
[29]
Jain SK, Jain AK, Rajpoot K. Expedition of Eudragit® polymers in the development of novel drug delivery systems. Curr Drug Deliv 2020; 17(6): 448-69.
[http://dx.doi.org/10.2174/1567201817666200512093639] [PMID: 32394836]
[30]
Jain A, Jain SK, Ganesh N, Barve J, Beg AM. Design and development of ligand-appended polysaccharidic nanoparticles for the delivery of oxaliplatin in colorectal cancer. Nanomedicine (Lond) 2010; 6(1): 179-90.
[http://dx.doi.org/10.1016/j.nano.2009.03.002] [PMID: 19447205]
[31]
Jain SK, Agrawal GP, Jain NK. A novel calcium silicate based microspheres of repaglinide: in vivo investigations. J Control Release 2006; 113(2): 111-6.
[http://dx.doi.org/10.1016/j.jconrel.2006.04.005] [PMID: 16759733]
[32]
Jain SK, Jangdey MS. Lectin conjugated gastroretentive multiparticulate delivery system of clarithromycin for the effective treatment of Helicobacter pylori. Mol Pharm 2009; 6(1): 295-304.
[http://dx.doi.org/10.1021/mp800193n] [PMID: 19093870]
[33]
Li X, Xu Y, Chen G, Wei P, Ping Q. PLGA nanoparticles for the oral delivery of 5-Fluorouracil using high pressure homogenization-emulsification as the preparation method and in vitro/in vivo studies. Drug Dev Ind Pharm 2008; 34(1): 107-15.
[http://dx.doi.org/10.1080/03639040701484593] [PMID: 18214762]
[34]
Mattos AC, Altmeyer C, Tominaga TT, Khalil NM, Mainardes RM. Polymeric nanoparticles for oral delivery of 5-fluorouracil: Formulation optimization, cytotoxicity assay and pre-clinical pharmacokinetics study. Eur J Pharm Sci 2016; 84: 83-91.
[http://dx.doi.org/10.1016/j.ejps.2016.01.012] [PMID: 26775869]
[35]
Khalil NM, Mainardes RM. Development and validation of an HPLC method for the determination of fluorouracil in polymeric nanoparticles. Braz J Pharm Sci 2013; 49: 117-26.
[http://dx.doi.org/10.1590/S1984-82502013000100013]
[36]
Pandey AN, Raj R, Ganesh N, Jain SK. Concanavalin-A Conjugated 5-Fluorouracil Loaded PLGA Nanoparticles: A Novel Approach for Effective Treatment of Colorectal Cancer. Res J Pharm Tech 2018; 11: 2782-91.
[http://dx.doi.org/10.5958/0974-360X.2018.00514.0]
[37]
Joshi G, Kumar A, Sawant K. Enhanced bioavailability and intestinal uptake of Gemcitabine HCl loaded PLGA nanoparticles after oral delivery. Eur J Pharm Sci 2014; 60: 80-9.
[http://dx.doi.org/10.1016/j.ejps.2014.04.014] [PMID: 24810394]
[38]
Pandey AN, Rajpoot K, Jain SK. Using 5-fluorouracil-encored PLGA nanoparticles for the treatment of colorectal cancer: the in-vitro characterization and cytotoxicity studies. Nanomed J 2020; 7: 211-24.
[39]
Paharia A, Yadav AK, Rai G, Jain SK, Pancholi SS, Agrawal GP. Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting. AAPS PharmSciTech 2007; 8(1): 12.
[http://dx.doi.org/10.1208/pt0801012] [PMID: 17408212]


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Article Details

VOLUME: 11
ISSUE: 1
Year: 2021
Published on: 23 November, 2020
Page: [51 - 60]
Pages: 10
DOI: 10.2174/2468187310999201123195233
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