Kajian Pengembangan Sistem Nanocarrier Berbasis Lipid untuk Penghantaran Tamoxifen pada Terapi Endokrin Kanker Payudara
Abstract
Abstract. Tamoxifen is an antiestrogen that is the first line of endocrine therapy for breast cancer with HR+. The active substance has very low water solubility (about 0.3 mg/L) and metabolism in the liver, resulting in low bioavailability. Various lipid-based drug delivery systems can be developed to increase the effectiveness and reduce the side effects of tamoxifen. This study aims to determine the strategy for developing lipid-based nanocarrier systems in the form of liposomes, niosomes, SLNs, and NLCs in the delivery of tamoxifen, as well as to find the best nanocarrier system to increase the effectiveness and reduce the side effects of tamoxifen. This study was conducted using the Systematic Literature Review (SLR) method. The results showed that tamoxifen formulated in NLC form, with GMS as solid lipid components, olive oil as liquid lipids, POE-40-S as surfactant, PVA as co-surfactant, and prepared by microemulsion-cooling method provided the best characteristics of lipid-based nanocarrier systems, and stable. Liposome and NLC systems showed the greatest increase in the effectiveness of tamoxifen, marked by increased growth inhibition of MCF-7, MDA MB-231 cells, pharmacokinetic data (Cmax and AUC), and survival of the test animals. In addition, the development of lipid nanocarriers can also reduce the hepatotoxicity of tamoxifen, such as reducing ALT and AST levels.
Keywords: Tamoxifen, Nanocarrier, Lipids.
Abstrak. Tamoxifen merupakan antiestrogen yang menjadi first line untuk terapi endokrin kanker payudara dengan HR+. Zat aktif tersebut memiliki kelarutan dalam air yang sangat rendah (sekitar 0,3 mg/L) dan mengalami metabolisme di hati, sehingga bioavailabilitasnya rendah. Berbagai sistem penghantaran obat berbasis lipid dapat dikembangkan untuk mencapai peningkatan efektifitas dan penurunan efek samping tamoxifen. Kajian ini bertujuan untuk mengetahui strategi pengembangan sistem nanocarrier berbasis lipid dalam bentuk liposom, niosom, SLN, dan NLC dalam penghantaran tamoxifen, serta mendapatkan sistem nanocarrier yang paling baik untuk meningkatkan efektifitas dan menurunkan efek samping tamoxifen. Kajian ini dilakukan dengan metode Systematic Literature Review (SLR). Hasil kajian menunjukkan bahwa tamoxifen yang diformulasikan dalam bentuk NLC, dengan komponen lipid padat GMS, lipid cair minyak zaitun, surfaktan POE-40-S dan ko-surfaktan PVA, serta dibuat dengan metode mikroemulsi-pendinginan memberikan karakteristik sistem nanocarrier berbasis lipid yang paling baik dan stabil. Sistem liposom dan NLC menunjukkan peningkatan efektifitas tamoxifen yang paling besar ditandai dengan meningkatnya penghambatan pertumbuhan sel MCF-7, MDA MB-231, data farmakokinetik (Cmax dan AUC), serta kelangsungan hidup hewan uji. Selain itu, pengembangan lipid nanocarrier juga dapat mengurangi hepatotoksik tamoxifen, seperti menurunkan kadar ALT dan AST.
Kata Kunci: Tamoxifen, Nanocarrier, Lipid.
References
[2] Anjum, R., & Lakshmi, P. K. (2019). A REVIEW ON SOLID LIPID NANOPARTICLES; FOCUS ON EXCIPIENTS AND FORMULATION TECHNIQUES. International Journal of Pharmaceutical Sciences and Research, 10(9), 4090. https://doi.org/10.13040/IJPSR.0975-8232.10(9).4090-99
[3] Asthana, G. S., Sharma, P. K., & Asthana, A. (2016). In Vitro and in Vivo Evaluation of Niosomal Formulation for Controlled Delivery of Clarithromycin. Scientifica, 2016. https://doi.org/10.1155/2016/6492953
[4] Barhoum, A., García-Betancourt, M. L., Rahier, H., & Van Assche, G. (2018). Physicochemical characterization of nanomaterials: Polymorph, composition, wettability, and thermal stability. In Emerging Applications of Nanoparticles and Architectural Nanostructures: Current Prospects and Future Trends (pp. 255–278). Elsevier Inc. https://doi.org/10.1016/B978-0-323-51254-1.00009-9
[5] Bulbake, U., Doppalapudi, S., Kommineni, N., & Khan, W. (2017). Liposomal formulations in clinical use: An updated review. In Pharmaceutics (Vol. 9, Issue 2). MDPI AG. https://doi.org/10.3390/pharmaceutics9020012
[6] Chauhan, I., Yasir, M., Verma, M., & Singh, A. P. (2020). Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery. In Advanced Pharmaceutical Bulletin (Vol. 10, Issue 2, pp. 150–165). Tabriz University of Medical Sciences. https://doi.org/10.34172/apb.2020.021
[7] Dhaundiyal, A., Jena, S. K., Samal, S. K., Sonvane, B., Chand, M., & Sangamwar, A. T. (2016). Alpha-lipoic acid–stearylamine conjugate-based solid lipid nanoparticles for tamoxifen delivery: formulation, optimization, in-vivo pharmacokinetic and hepatotoxicity study. Journal of Pharmacy and Pharmacology, 68(12), 1535–1550. https://doi.org/10.1111/jphp.12644
[8] El-Leithy, E. S., Hassan, S. A., & Abdel-Rashid, R. S. (2019). Tamoxifen citrate/Coenzyme Q10 as smart nanocarriers Bitherapy for Breast Cancer: Cytotoxicity, genotoxicity, and antioxidant activity. Journal of Drug Delivery Science and Technology, 51, 36–44. https://doi.org/10.1016/j.jddst.2019.02.010
[9] Elsewedy, H. S., Shehata, T. M., Almostafa, M. M., & Soliman, W. E. (2022). Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin. Nanomaterials, 12(13). https://doi.org/10.3390/nano12132160
[10] Ganesan, P., & Narayanasamy, D. (2017). Lipid nanoparticles: Different preparation techniques, characterization, hurdles, and strategies for the production of solid lipid nanoparticles and nanostructured lipid carriers for oral drug delivery. In Sustainable Chemistry and Pharmacy (Vol. 6, pp. 37–56). Elsevier B.V. https://doi.org/10.1016/j.scp.2017.07.002
[11] Gordon, J., Brown, M., & Reynolds, M. (2018). Cell-Based Methods for Determination of Efficacy for Candidate Therapeutics in the Clinical Management of Cancer. Diseases, 6(4), 85. https://doi.org/10.3390/diseases6040085
[12] International Agency for Research on Cancer Globocan (2020). Indonesia. https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf
[13] Iwa, T. N., Hata, T., Hayashi, M., & Imagawa, Y. (2016). Evaluation of the Pharmacokinetic parameters of standard oral antibiotics in a bioequivalence study of generic products. In Pharmazie (Vol. 71, Issue 7, pp. 363–377). Govi-Verlag Pharmazeutischer Verlag GmbH. https://doi.org/10.1691/ph.2016.6557
[14] Jacquet, E., Lardy-Cléaud, A., Pistilli, B., Franck, S., Cottu, P., Delaloge, S., Debled, M., Vanlemmens, L., Leheurteur, M., Guizard, A. V., Laborde, L., Uwer, L., Jacot, W., Berchery, D., Desmoulins, I., Ferrero, J. M., Perrocheau, G., Courtinard, C., Brain, E., … Bachelot, T. (2018). Endocrine therapy or chemotherapy as first-line therapy in hormone receptor–positive HER2-negative metastatic breast cancer patients. European Journal of Cancer, 95, 93–101. https://doi.org/10.1016/j.ejca.2018.03.013
[15] Jain, A. S., Goel, P. N., Shah, S. M., Dhawan, V. V., Nikam, Y., Gude, R. P., & Nagarsenker, M. S. (2014). Tamoxifen guided liposomes for targeting encapsulated anticancer agent to estrogen receptor positive breast cancer cells: In vitro and in vivo evaluation. Biomedicine and Pharmacotherapy, 68(4), 429–438. https://doi.org/10.1016/j.biopha.2014.03.004
[16] Jose, A., Ninave, K. M., Karnam, S., & Venuganti, V. V. K. (2019). Temperature-sensitive liposomes for co-delivery of tamoxifen and imatinib for synergistic breast cancer treatment. Journal of Liposome Research, 29(2), 153–162. https://doi.org/10.1080/08982104.2018.1502315
[17] Krambeck, K., Silva, V., Silva, R., Fernandes, C., Cagide, F., Borges, F., Santos, D., Otero-Espinar, F., Lobo, J. M. S., & Amaral, M. H. (2021). Design and characterization of Nanostructured lipid carriers (NLC) and Nanostructured lipid carrier-based hydrogels containing Passiflora edulis seeds oil. International Journal of Pharmaceutics, 600. https://doi.org/10.1016/j.ijpharm.2021.120444
[18] Kulkarni, P., & Rawtani, D. (2019). Application of Box-Behnken Design in the Preparation, Optimization, and In Vitro Evaluation of Self-Assembly–Based Tamoxifen- and Doxorubicin-Loaded and Dual Drug–Loaded Niosomes for Combinatorial Breast Cancer Treatment. Journal of Pharmaceutical Sciences, 108(8), 2643–2653. https://doi.org/10.1016/j.xphs.2019.03.020
[19] Nsairat, H., Khater, D., Sayed, U., Odeh, F., Al Bawab, A., & Alshaer, W. (2022). Liposomes: structure, composition, types, and clinical applications. In Heliyon (Vol. 8, Issue 5). Elsevier Ltd. https://doi.org/10.1016/j.heliyon.2022.e09394
[20] Poovi, G., & Damodharan, N. (2020). Development of tamoxifen-loaded surfacemodified nanostructured lipid carrier using experimental design: In vitro and ex vivo characterisation. IET Nanobiotechnology, 14(4), 261–274. https://doi.org/10.1049/iet-nbt.2019.0276
[21] Safwat, S., Ishak, R. A. H., Hathout, R. M., & Mortada, N. D. (2017). Nanostructured lipid carriers loaded with simvastatin: effect of PEG/glycerides on characterization, stability, cellular uptake efficiency and in vitro cytotoxicity. Drug Development and Industrial Pharmacy, 43(7), 1112–1125. https://doi.org/10.1080/03639045.2017.1293681
[22] Samimi, S., Maghsoudnia, N., Eftekhari, R. B., & Dorkoosh, F. (2018). Lipid-Based Nanoparticles for Drug Delivery Systems. In Characterization and Biology of Nanomaterials for Drug Delivery: Nanoscience and Nanotechnology in Drug Delivery (pp. 47–76). Elsevier. https://doi.org/10.1016/B978-0-12-814031-4.00003-9
[23] Sguizzato, M., Subroto, E., Andoyo, R., & Indiarto, R. (2023). Academic Editors: Rita Cortesi and Solid Lipid Nanoparticles: Review of the Current Research on Encapsulation and Delivery Systems for Active and Antioxidant Compounds. https://doi.org/10.3390/10.3390/antiox12030633
[24] Shaker, D. S., Shaker, M. A., & Hanafy, M. S. (2015). Cellular uptake, cytotoxicity and in-vivo evaluation of Tamoxifen citrate loaded niosomes. International Journal of Pharmaceutics, 493(1–2), 285–294. https://doi.org/10.1016/j.ijpharm.2015.07.041
[25] Shete, H., Chatterjee, S., De, A., & Patravale, V. (2013). Long chain lipid based tamoxifen NLC. Part II: Pharmacokinetic, biodistribution and in vitro anticancer efficacy studies. International Journal of Pharmaceutics, 454(1), 584–592. https://doi.org/10.1016/j.ijpharm.2013.03.036
[26] Shete, H. K., Selkar, N., Vanage, G. R., & Patravale, V. B. (2014). Tamoxifen nanostructured lipid carriers: Enhanced in vivo antitumor efficacy with reduced adverse drug effects. International Journal of Pharmaceutics, 468(1–2), 1–14. https://doi.org/10.1016/j.ijpharm.2014.03.056
[27] Wang, X., Chen, X., Yang, X., Gao, W., He, B., Dai, W., Zhang, H., Wang, X., Wang, J., Zhang, X., Dai, Z., & Zhang, Q. (2016). A nanomedicine based combination therapy based on QLPVM peptide functionalized liposomal tamoxifen and doxorubicin against Luminal A breast cancer. Nanomedicine: Nanotechnology, Biology, and Medicine, 12(2), 387–397. https://doi.org/10.1016/j.nano.2015.12.360
[28] Zhang, H. (2017). Thin-film hydration followed by extrusion method for liposome preparation. In Methods in Molecular Biology (Vol. 1522, pp. 17–22). Humana Press Inc. https://doi.org/10.1007/978-1-4939-6591-5_2
