THE FORMULATION AND EVALUATION OF 6-THIOGUANINE AS A NANOSTRUCTURE LIPID CARRIER FOR THE TARGETED DELIVERY OF BREAST CANCER

Authors

  • ALAA A. HASHIM Pharmaceutics Department, College of Pharmacy, Ahlal-Bayt University, Karbala, Iraq https://orcid.org/0009-0000-9757-7620
  • DHIYA ALTEMEMY Department of Pharmaceutics, College of Pharmacy, Al-Zahraa University for Women, Karbala, Iraq
  • HUSSEIN ABDELAMIR MOHAMMAD 3. Pharmaceutics Department, College of Pharmacy, University of Al-Qadisyiah, Al-Qadisyiah, Iraq
  • HASANAIN SHAKIR MAHMOOD University of Alkafeel – College of Pharmacy, Al-Najaf, Iraq
  • RADHWAN M. HUSSEIN Pharmaceutics Department, College of Pharmacy, Ahlal-Bayt University, Karbala, Iraq https://orcid.org/0000-0002-2318-8689
  • MAHSA REZAEI Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • PEGAH KHOSRAVIAN Medical Plants Research Centre, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran

DOI:

https://doi.org/10.22159/ijap.2024v16i3.50379

Keywords:

Breast cancer, Thioguanine (TG), Nanostructured lipid carriers (NLCs), Polydispersity index, Zeta potential

Abstract

Objective:  The main goal was to avoid all the problems associated with usual breast cancer treatment by using 6-thioguanine as a nanostructure lipid carrier (TG-NLCS). This was accomplished by administering an effective and targeted dose of 6-thioguanine (TG) to the tumour site using a long-lasting and biodegradable delivery system.

Methods: A combination of heat homogenization and ultrasonication was used to implement the emulsification process. To obtain the optimal formulation, the prepared formulations were first assessed for particle size, Polydispersity Index (PDI), zeta potential, entrapment efficiency, and drug loading capacity. Additionally, a range of physicochemical characterization techniques were employed, including dissolution studies, melting point determination, Fourier-Transform Infrared (FTIR) spectroscopy, and Field Emission Scanning Electron Microscopy (FESEM), as well as cytotoxicity assessment of TG-NLCs in MCF-7 breast cancer cells.

Results: The selected formula, TG03, showed a zeta potential of-13.5±0.27 mV and a particle size of 149±0.55 nm. This was further examined using a FESEM. In the in vitro drug release study, the formula demonstrated better-controlled drug release for 48 h in comparison to other formulations. In addition, the significant anti-proliferation activity of TG-NLCs against the MCF-7 breast cancer cell line.

Conclusion: Nanostructured lipid carriers (NLCs) are one type of multifunctional nanoparticle that includes many combinations of lipids and medicines for various delivery routes.

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References

Mosleh Shirazi S, Abbasi M, Moaddeli MR, Vaez A, Shafiee M, Kasaee SR. Nanotechnology advances in the detection and treatment of cancer: an overview. Nanotheranostics. 2022;6(4):400-23. doi: 10.7150/ntno.74613, PMID 36051855.

Karimi Maleh H, Fallah Shojaei A, Karimi F, Tabatabaeian K, Shakeri S. Au nanoparticle loaded with 6-thioguanine anticancer drug as a new strategy for drug delivery. J Nanostruct. 2018;8(4):217-424.

Martindale BA. The complete drug reference. 39th ed. UK: Pharmaceutical Press; 2017. p. 871.

Luengo A, Gui DY, Vander Heiden MG. Targeting metabolism for cancer therapy. Cell Chem Biol. 2017;24(9):1161-80. doi: 10.1016/j.chembiol.2017.08.028, PMID 28938091.

Ford LT, Berg JD. Thiopurine S-methyltransferase (TPMT) assessment prior to starting thiopurine drug treatment; a pharmacogenomic test whose time has come. J Clin Pathol. 2010;63(4):288-95. doi: 10.1136/jcp.2009.069252, PMID 20354201.

Selvamuthukumar S, Velmurugan R. Nanostructured lipid carriers: a potential drug carrier for cancer chemotherapy. Lipids Health Dis. 2012;11(1):159. doi: 10.1186/1476-511X-11-159, PMID 23167765.

Elmowafy M, Al-Sanea MM. Nanostructured lipid carriers (NLCs) as drug delivery platform: advances in formulation and delivery strategies. Saudi Pharm J. 2021;29(9):999-1012. doi: 10.1016/j.jsps.2021.07.015, PMID 34588846.

Beale JM, Block JH. Organic medicinal and pharmaceutical chemistry. 12th ed. Wolters Kluwer Health; 2011. p. 378.

Convention USP U. S. Pharmacopoeia 2020. USP. NF 38 Convention. Vol. 43. United States Pharmacopeial; 2020. p. 6497.

Grabowska Jadach I, Drozd M, Kulpińska D, Komendacka K, Pietrzak M. Modification of fluorescent nanocrystals with 6-thioguanine: monitoring of drug delivery. Appl Nanosci. 2020;10(1):83-93. doi: 10.1007/s13204-019-01101-6.

Gilda SS, Kolling WM, Nieto M, McPherson T. Stability and beyond-use date of a compounded thioguanine suspension. J Pharm Technol. 2021;37(1):23-9. doi: 10.1177/8755122520952436, PMID 34752544.

Huang R, Li J, Kebebe D, Wu Y, Zhang B, Liu Z. Cell penetrating peptides functionalized gambogic acid-nanostructured lipid carrier for cancer treatment. Drug Deliv. 2018;25(1):757-65. doi: 10.1080/10717544.2018.1446474, PMID 29528244.

Gao W, Meng T, Shi N, Zhuang H, Yang Z, Qi X. Targeting and microenvironment-responsive lipid nanocarrier for the enhancement of tumor cell recognition and therapeutic efficiency. Adv Healthc Mater. 2015;4(5):748-59. doi: 10.1002/adhm.201400675, PMID 25522298.

Ma Z, Li N, Zhang B, Hui Y, Zhang Y, Lu P. Dual drug-loaded nano-platform for targeted cancer therapy: toward clinical therapeutic efficacy of multifunctionality. J Nanobiotechnology. 2020;18(1):123. doi: 10.1186/s12951-020-00681-8, PMID 32887626.

Shinde AJ, Tarlekar SD, Jarag RJ, Tamboli FA. Antipsoriatic activity of hydrogel containing nanostructured lipid carrier (Nlc) entrapped with triamcinolone acetonide. Int J App Pharm. 2023;15(1):308-17. doi: 10.22159/ijap.2023v15i1.46198.

Kesharwani R, Patel DK, Yadav PK. Bioavailability enhancement of repaglinide using nano lipid carrier: preparation characterization and in vivo evaluation. Int J App Pharm. 2022;14(5):181-9. doi: 10.22159/ijap.2022v14i5.45032.

Dong Z, Iqbal S, Zhao Z. Preparation of ergosterol-loaded nanostructured lipid carriers for enhancing oral bioavailability and antidiabetic nephropathy effects. AAPS PharmSciTech. 2020;21(2):64. doi: 10.1208/s12249-019-1597-3, PMID 31932990.

Alhamdany AT, Abbas AK. Formulation and in vitro evaluation of amlodipine gastroretentive floating tablets using a combination of hydrophilic and hydrophobic polymers. Int J App Pharm. 2018;10(6):126-34. doi: 10.22159/ijap.2018v10i6.28687.

Tekade RK. Basic fundamentals of drug delivery. Academic Press; 2018. p. 369-400.

Aghevlian S, Yousefi R, Faghihi R, Abbaspour A, Niazi A, Jaberipour M. The improvement of anti-proliferation activity against breast cancer cell line of thioguanine by gold nanoparticles. Med Chem Res. 2013;22(1):303-11. doi: 10.1007/s00044-012-0030-1.

Hasanzadeh D, Mahdavi M, Dehghan G, Charoudeh HN. Farnesiferol C induces cell cycle arrest and apoptosis mediated by oxidative stress in MCF-7 cell line. Toxicol Rep. 2017;4:420-6. doi: 10.1016/j.toxrep.2017.07.010, PMID 28959668.

Rahman HS, Rasedee A, How CW, Abdul AB, Zeenathul NA, Othman HH. Zerumbone-loaded nanostructured lipid carriers: preparation, characterization, and antileukemic effect. Int J Nanomedicine. 2013;8:2769-81. doi: 10.2147/IJN.S45313, PMID 23946649.

Aykul S, Martinez Hackert E. Determination of half-maximal inhibitory concentration using biosensor-based protein interaction analysis. Anal Biochem. 2016;508:97-103. doi: 10.1016/j.ab.2016.06.025, PMID 27365221.

Chatterjee M, Jaiswal N, Hens A, Mahata N, Chanda N. Development of 6-thioguanine conjugated PLGA nanoparticles through thioester bond formation: benefits of electrospray mediated drug encapsulation and sustained release in cancer therapeutic applications. Mater Sci Eng C Mater Biol Appl. 2020;114:111029. doi: 10.1016/j.msec.2020.111029, PMID 32994006.

McHugh ML. Multiple comparison analysis testing in ANOVA. Biochem Med (Zagreb). 2011;21(3):203-9. doi: 10.11613/bm.2011.029, PMID 22420233.

Budavari S. The merck index: an encyclopedia of chemicals, drugs, and BioLogicals. 11th ed. Merck; 1989. p. 1470.

Castegnaro M, Barek J, Dennis J, Ellen G, Klibanov M, Lafontaine M. Laboratory decontamination and destruction of carcinogens in laboratory wastes: some aromatic amines and 4-nitrobiphenyl. IARC Sci Publ. 1985;64:1-85. PMID 4065953.

Li Q, Cai T, Huang Y, Xia X, Cole SPC, Cai Y. A review of the structure, preparation, and application of NLCs, PNPs, and PLNs. Nanomaterials (Basel). 2017;7(6):122. doi: 10.3390/nano7060122, PMID 28554993.

Kuo CH, Chiang TF, Chen LJ, Huang MH. Synthesis of highly faceted pentagonal- and hexagonal-shaped gold nanoparticles with controlled sizes by sodium dodecyl sulfate. Langmuir. 2004;20(18):7820-4. doi: 10.1021/la049172q, PMID 15323536.

Cho EC, Zhang Q, Xia Y. The effect of sedimentation and diffusion on cellular uptake of gold nanoparticles. Nat Nanotechnol. 2011;6(6):385-91. doi: 10.1038/nnano.2011.58, PMID 21516092.

Pan Y, Neuss S, Leifert A, Fischler M, Wen F, Simon U. Size-dependent cytotoxicity of gold nanoparticles. Small. 2007;3(11):1941-9. doi: 10.1002/smll.200700378, PMID 17963284.

Gupta S, Kesarla R, Chotai N, Misra A, Omri A. Systematic approach for the formulation and optimization of solid lipid nanoparticles of efavirenz by high pressure homogenization using design of experiments for brain targeting and enhanced bioavailability. BioMed Res Int. 2017;2017:5984014. doi: 10.1155/2017/5984014, PMID 28243600.

Haider M, Abdin SM, Kamal L, Orive G. Nanostructured lipid carriers for delivery of chemotherapeutics: a review. Pharmaceutics. 2020;12(3):288. doi: 10.3390/pharmaceutics12030288, PMID 32210127.

Nakamura Y, Mochida A, Choyke PL, Kobayashi H. Nanodrug delivery: is the enhanced permeability and retention effect sufficient for curing cancer? Bioconjug Chem. 2016;27(10):2225-38. doi: 10.1021/acs.bioconjchem.6b00437, PMID 27547843.

Gunasekaran S, Kumaresan S, Arunbalaji R, Anand G, Seshadri S, Muthu S. Vibrational assignments and electronic structure calculations for 6‐thioguanine. J Raman Spectroscopy. 2009;40(11):1675-81. doi: 10.1002/jrs.2318.

Ji P, Yu T, Liu Y, Jiang J, Xu J, Zhao Y. Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics. Drug Des Devel Ther. 2016;10:911-25. doi: 10.2147/DDDT.S97738, PMID 27041995.

Fang CL, Al-Suwayeh SA, Fang JY. Nanostructured lipid carriers (NLCs) for drug delivery and targeting. Recent Pat Nanotechnol. 2013;7(1):41-55. doi: 10.2174/187221013804484827, PMID 22946628.

Chinsriwongkul A, Chareanputtakhun P, Ngawhirunpat T, Rojanarata T, Sila-on W, Ruktanonchai U. Nanostructured lipid carriers (NLC) for parenteral delivery of an anticancer drug. AAPS PharmSciTech. 2012;13(1):150-8. doi: 10.1208/s12249-011-9733-8, PMID 22167418.

Alkilany AM, Thompson LB, Boulos SP, Sisco PN, Murphy CJ. Gold nanorods: their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions. Adv Drug Deliv Rev. 2012;64(2):190-9. doi: 10.1016/j.addr.2011.03.005, PMID 21397647.

Podsiadlo P, Sinani VA, Bahng JH, Kam NW, Lee J, Kotov NA. Gold nanoparticles enhance the anti-leukemia action of a 6-mercaptopurine chemotherapeutic agent. Langmuir. 2008;24(2):568-74. doi: 10.1021/la702782k, PMID 18052300.

Published

07-05-2024

How to Cite

HASHIM, A. A., ALTEMEMY, D., MOHAMMAD, H. A., MAHMOOD, H. S., M. HUSSEIN, R., REZAEI, M., & KHOSRAVIAN, P. (2024). THE FORMULATION AND EVALUATION OF 6-THIOGUANINE AS A NANOSTRUCTURE LIPID CARRIER FOR THE TARGETED DELIVERY OF BREAST CANCER. International Journal of Applied Pharmaceutics, 16(3), 167–175. https://doi.org/10.22159/ijap.2024v16i3.50379

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