Nanostructured Lipid Carriers Termodifikasi Kitosan dari Cangkang Keong Mas (Pomacea canaliculata) sebagai Penghantar Obat Kurkumin yang Terkontrol dan Tertargret Sel Kanker Payudara
Abstract
Pengobatan kanker payudara saat ini masih sangat bergantung pada kemoterapi yang memiliki efek samping fisik dan psikologis. Kurkumin mudah terdegradasi dan memiliki biavaibilitas yang rendah. Kurkumin adalah senyawa lipofilik yang stabilitasnya dapat ditingkatkan dengan menggunakan sistem penghantaran obat berbasis Nanostructured Lipid Carriers (NLCs) yang dimodifikasi dengan kitosan untuk melindungi bahan tersebut dari degradasi dalam sistem oral. Asam folat juga digunakan untuk menargetkan sel kanker payudara T47D. Kitosan disintesis dari cangkang keong mas menghasilkan bubuk putih (32,28%) dengan derajat deasetilasi 76,55%. Kitosan dikonjugasikan dengan asam folat (Chi-FA). Material NLCs termuat kurkumin disintesis melalui reaksi emulsi-evaporasi-solidifikasi. Material NLCs termuat kurkumin (Cur@NLCs) menunjukkan dua model matriks berdasarkan uji transmitansinya dengan distribusi ukuran partikel sebesar 174,4 nm dan zeta potensial -56,9 mV. Modifikasi permukaan Cur@NLCs dengan Chi-FA menghasilkan ukuran partikel 105,5 nm dan potensial zeta -45,9 mV. Studi pelepasan menunjukkan bahwa keberadaan kitosan dapat menekan pelepasan kurkumin dalam phosphate buffered saline (PBS) pada pH 1,2 dan pH 7,4 serta meningkatkan laju pelepasan pada pH 6,8. Uji toksisitas material menunjukkan peningkatan toksisitas pada sel T-47D. Penelitian ini menunjukkan bahwa modifikasi tersebut dapat mengontrol dan menargetkan sel kanker.
Nanostructured Lipid Carriers Modified with Chitosan from Golden Apple Snail Shells (Pomacea canaliculata) as Controlled and Targeted Curcumin Drug Delivery for Breast Cancer Cells. Current breast cancer treatment still relies heavily on chemotherapy, which has physical and psychological side effects. Curcumin is easily degraded and has low bioavailability. Curcumin is a lipophilic compound whose stability can be improved by using Nanostructured Lipid Carriers (NLCs)-based drug delivery systems modified with chitosan to protect the material from degradation in the oral system. Folic acid is also used to target T47D breast cancer cells. Chitosan was synthesized from golden apple snail shells to produce a white powder (32.28%) with a deacetylation degree of 76.55%. The chitosan was conjugated with folic acid (Chi-FA). Curcumin-loaded NLCs were synthesized through an emulsion-evaporation-solidification reaction. Curcumin-loaded NLCs (Cur@NLCs) showed two matrix models based on the transmittance test with a particle size distribution of 174.4 nm and a zeta potential of -56.9 mV. Surface modification of Cur@NLCs with Chi-FA resulted in a particle size of 105.5 nm and a zeta potential of -45.9 mV. Release studies showed that the presence of chitosan could suppress the release of curcumin in PBS at pH 1.2 and pH 7.4, and increase the release rate at pH 6.8. The material toxicity test showed an increase in toxicity to T-47D cells. This study shows that the modification can control and target cancer cells.
Keywords
References
Aboelela, M.M., Abd El-Ghany, N.A., and Elsabee, M.Z., 2023. Surface Modification of Polypropylene by Grafting Films for Active Food Packaging. Egyptian Journal of Chemistry, 66, 439–458. https://doi.org/10.21608/EJCHEM.2023.173356.7168.
Alimi, B.A., Pathania, S., Wilson, J., Duffy, B., and Frias, J.M.C., 2023. Extraction, Quantification, Characterization, and Application in Food Packaging of Chitin and Chitosan from Mushrooms: A Review. International Journal of Biological Macromolecules, 237, 124195. https://doi.org/10.1016/j.ijbiomac.2023.124195.
Anand, U., Dey, A., Chandel, A.K.S., Sanyal, R., Mishra, A., Pandey, D.K., De Falco, V., Upadhyay, A., Kandimalla, R., Chaudhary, A., Dhanjal, J.K., Dewanjee, S., Vallamkondu, J., and Pérez de la Lastra, J.M., 2023. Cancer Chemotherapy and beyond: Current Status, Drug Candidates, Associated Risks and Progress in Targeted Therapeutics. Genes and Diseases, 10, 1367–1401. https://doi.org/10.1016/j.gendis.2022.02.007.
Ariyanti, A., Masruriati, E., Imadahidayah, T., and Sulistianingsih, E.N., 2020. Pemanfaatan Kitosan dari Cangkang Kerang Bulu (Anadara Antiquata) sebagai Pengawet Ikan Pari (Dasyatis sp.) dan Udang Vaname (Litopenaeus vannamei). Riset Informasi Kesehatan, 9, 12–21. https://doi.org/10.30644/rik.v9i1.241.
Aspadiah, V., Fristiohady, A., and Wahyuningrum, S.N., 2020. Review Artikel: Penggunaan Lipid Asam Stearat dalam Sistem Penghantaran Obat Berbasis Nanopartikel. Media Farmasi, 16, 141–154. https://doi.org/10.32382/mf.v16i2.1622.
Ayu, L. S., Rosida, D. F., Kongpichitchoke, T., Priyanto, A. D., and Putra, A. Y. T., 2023. Physicochemical Properties of Golden Apple Snail (Pomacea canaliculata) Shell Chitosan. Food Science and Technology Journal (Foodscitech), 6, 51-60.
Barcelos, K.A., Mendonça, C.R., Noll, M., Botelho, A.F., Francischini, C.R.D., and Silva, M.A.M., 2022. Antitumor Properties of Curcumin in Breast Cancer Based on Preclinical Studies: A Systematic Review. Cancers, 14, 1–36. https://doi.org/10.3390/cancers14092165.
Bellotti, E., Cascone, M.G., Barbani, N., Rossin, D., Rastaldo, R., Giachino, C., and Cristallini, C., 2021. Targeting Cancer Cells Overexpressing Folate Receptors with New Terpolymer-Based Nanocapsules: Toward a Novel Targeted DNA Delivery System for Cancer Therapy. Biomedicines, 9, 1275. https://doi.org/10.3390/biomedicines9091275.
Elkhateeb, O., Badawy, M.E.I., Tohamy, H.G., Abou-Ahmed, H., El-Kammar, M., and Elkhenany, H., 2023. Curcumin-Infused Nanostructured Lipid Carriers: A Promising Strategy for Enhancing Skin Regeneration and Combating Microbial Infection. BMC Veterinary Research, 19, 1–13. https://doi.org/10.1186/s12917-023-03774-2.
Fatnah, N., Azizah, D., and Cahyani, M.D., 2020. Synthesis of Chitosan from Crab’s Shell Waste (Portunus pelagicus) in Mertasinga-Cirebon. In: International Conference on Progressive Education. ICOPE, 2019, pp. 370–375. https://doi.org/10.2991/assehr.k.200323.152.
Fauziah, N.A.N., Priani, S.E., and Mulyanti, D., 2022. Kajian Pengembangan Sediaan Nanokapsul Terkonjugasi Asam Folat untuk Penghantaran Tertarget Agen Sitotoksik pada Terapi Kanker. In: Bandung Conference Series: Pharmacy, 2, 281–290. https://doi.org/10.29313/bcsp.v2i2.4137.
Hassan, D.M., El-Kamel, A.H., Allam, E.A., Bakr, B.A., and Ashour, A.A., 2024. Chitosan-Coated Nanostructured Lipid Carriers for Effective Brain Delivery of Tanshinone IIA in Parkinson’s Disease: Interplay between Nuclear Factor-Kappa β and Cathepsin B. Drug Delivery and Translational Research, 14, 400–417. https://doi.org/10.1007/s13346-023-01407-7.
Hyun, J.E., Yi, H.Y., Hong, G.P., and Chun, J.Y., 2022. Digestion Stability of Curcumin-Loaded Nanostructured Lipid Carrier. LWT, 162, 113474. https://doi.org/10.1016/j.lwt.2022.113474.
Jin, K.T., Lan, H.R., Chen, X.Y., Wang, S.B., Ying, X.J., Lin, Y., and Mou, X.Z., 2019. Recent Advances in Carbohydrate-Based Cancer Vaccines. Biotechnology Letters, 41, 641–650. https://doi.org/10.1007/s10529-019-02675-5.
Kanani, N., Wardhono, E.Y., Adiwibowo, M.T., Pinem, M.P., Wardalia, W., Demustila, H., Farhan, M., and Anwari, R., 2023. Ekstraksi Kitosan Berbasis Cangkang Keong Mas (Pomacea canaliculata) Menggunakan Gelombang Ultrasonikasi. Jurnal Integrasi Proses, 12, 73–80. https://doi.org/10.36055/jip.v12i2.22217.
Kepekçi, R.A., Yener İlçe, B., and Demir Kanmazalp, S., 2021. Plant-Derived Biomaterials for Wound Healing. Studies in Natural Products Chemistry. pp. 227–264. https://doi.org/10.1016/B978-0-12-819489-8.00001-6.
Kumbhar, S.T., Patil, R.Y., Bhatia, M.S., Choudhari, P.B., and Gaikwad, V.L., 2022. Synthesis and Characterization of Chitosan Nanoparticles Decorated with Folate and Loaded with Dasatinib for Targeting Folate Receptors in Cancer Cells. OpenNano, 7, 100043. https://doi.org/10.1016/j.onano.2022.100043.
Lohan, S., Verma, R., Kaushik, D., and Bhatia, M., 2023. Optimization and Evaluation of Microwave-Assisted Curcumin-Loaded Nanostructured Lipid Carriers: A Green Approach. Future Journal of Pharmaceutical Sciences, 9, 117. https://doi.org/10.1186/s43094-023-00572-3.
Mashuni, M., Ritonga, H., Jahiding, M., and Hamid, F.H., 2022. Sintesis Kitosan dari Kulit Udang sebagai Bahan Membran Elektrode Au/Kitosan/GTA/AChE untuk Deteksi Pestisida. ALCHEMY Jurnal Penelitian Kimia, 18, 112–121. https://doi.org/10.20961/alchemy.18.1.56551.112-121.
Mursal, I.L.P., and Latipah, T., 2022. Pengaruh Variasi Suhu Deasetilasi terhadap Karakteristik Kitosan dari Limbah Cangkang Siput Sawah (Filopaludina javanica). In: Prosiding Seminar Nasional Diseminasi Hasil Penelitian Program Studi S1 Farmasi. Desember 2022, Tasikmalaya, Indonesia, pp. 304–314.
Naeeni, N.B., Tabrizi, M.H., Karimi, E., and Ghafaripour, H., 2024. Synthesis and Characterization of Liposomal Nanoparticles Coated with Chitosan–Folate for Efficient Delivery of Lawsone to Pancreatic Cancer Cells. Polymer Bulletin, 81, 2671–2683. https://doi.org/10.1007/s00289-023-04860-z.
Narmani, A., Rezvani, M., Farhood, B., Darkhor, P., Mohammadnejad, J., Amini, B., Refahi, S., and Abdi Goushbolagh, N., 2019. Folic Acid Functionalized Nanoparticles as Pharmaceutical Carriers in Drug Delivery Systems. Drug Development Research, 80, 404–424. https://doi.org/10.1002/ddr.21545.
Nguyen, D.T., Nguyen, T.P., Dinh, V.T., Nguyen, N.H., Nguyen, K.T.H., Nguyen, T.H., Ngan, T.T., Nhi, T.T.Y., Le, B.H.T., Le Thi, P., Dang, L.H., and Tran, N.Q., 2023. Potential from Synergistic Effect of Quercetin and Paclitaxel Co-Encapsulated in the Targeted Folic–Gelatin–Pluronic P123 Nanogels for Chemotherapy. International Journal of Biological Macromolecules, 243, 1–20. https://doi.org/10.1016/j.ijbiomac.2023.125248.
Patel, P., Raval, M., Airao, V., Ali, N., Shazly, G.A., Khan, R., and Prajapati, B., 2024. Formulation of Folate Receptor-Targeted Silibinin-Loaded Inhalable Chitosan Nanoparticles by the QbD Approach for Lung Cancer Targeted Delivery. ACS Omega, 9, 10353–10370. https://doi.org/10.1021/acsomega.3c07954.
Rahman, M.A., Ali, Abuzer, Rahamathulla, M., Salam, S., Hani, U., Wahab, S., Warsi, M.H., Yusuf, M., Ali, Amena, Mittal, V., and Harwansh, R.K., 2023. Fabrication of Sustained Release Curcumin-Loaded Solid Lipid Nanoparticles (Cur-SLNs) as a Potential Drug Delivery System for the Treatment of Lung Cancer: Optimization of Formulation and In Vitro Biological Evaluation. Polymers, 15, 1–16. https://doi.org/10.3390/polym15030542.
Ramadhan, W., Islami, D., Iballa, B.D.M., Pratama, A., and Rizkiyani, A.D., 2024. Uji Aktivitas Antibakteri Nanoemulsi Ekstrak Etanol Daun Kelor (Moringa oleiferea Lam. L). JFARM - Jurnal Farmasi, 2, 28–35. https://doi.org/10.58794/jfarm.v2i1.654.
Sadeghi, S., Homayouni Tabrizi, M., and Farhadi, A., 2023. Folic Acid-Chitosan Coated Stylosin Nanostructured Lipid Carriers: Fabrication, in Vitro–in Vivo Assessment in Breast Malignant Cells. Journal of Biomaterials Science, Polymer Edition, 34, 791–809. https://doi.org/10.1080/09205063.2022.2145868.
Saedi, A., Rostamizadeh, K., Parsa, M., Dalali, N., and Ahmadi, N., 2018. Preparation and Characterization of Nanostructured Lipid Carriers as Drug Delivery System: Influence of Liquid Lipid Types on Loading and Cytotoxicity. Chemistry and Physics of Lipids, 216, 65–72. https://doi.org/10.1016/j.chemphyslip.2018.09.007.
Selvaraj, K., and Yoo, B.K., 2019. Curcumin-Loaded Nanostructured Lipid Carrier Modified with Partially Hydrolyzed Ginsenoside. AAPS PharmSciTech, 20, 252. https://doi.org/10.1208/s12249-019-1467-z.
Sianipar, E.A., Louisa, M., and Wanandi, S.I., 2018. Kurkumin Meningkatkan Sensitivitas Sel Kanker Payudara terhadap Tamoksifen Melalui Penghambatan Ekspresi P-Glikoprotein dan Breast Cancer Resistance Protein. Jurnal Farmasi Galenika (Galenika Journal of Pharmacy) (e-Journal), 4, 1–11. https://doi.org/10.22487/j24428744.2018.v4.i1.9209.
Soma, Y.V.A., Daniel, D., and Saleh, C., 2018. Penentuan Derajat Asilasi (DA) dengan Metode Base Line dari Sintesis N-Aldimin Kitosan. Jurnal Atomik, 3, 9–12.
Sudjarwo, S., Bobsaid, J., Windianto, F.R., Rizkyah, C., Shaffiqa, N., Putra, A.S., Jaelani, M.I., Zulfah, Y., Nareswari, A.B., Fridayanti, S.I., Devitri, N.A., Yakub, N., Putri, Y.B.P., and Widyowati, R., 2023. Improving the Bioavailability of Curcumin in Curcuma Heyneana by Preparing Solid Dispersion. Berkala Ilmiah Kimia Farmasi, 10, 23–27. https://doi.org/10.20473/bikfar.v10i1.44546.
Tang, C.H., Chen, H. Le, and Dong, J.R., 2023. Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) as Food-Grade Nanovehicles for Hydrophobic Nutraceuticals or Bioactives. Applied Sciences (Switzerland), 13, 1726. https://doi.org/10.3390/app13031726.
Ullah, S., Azad, A.K., Nawaz, A., Shah, K.U., Iqbal, M., Albadrani, G.M., Al-Joufi, F.A., Sayed, A.A., and Abdel-Daim, M.M., 2022. 5-Fluorouracil-Loaded Folic-Acid-Fabricated Chitosan Nanoparticles for Site-Targeted Drug Delivery Cargo. Polymers, 14. https://doi.org/10.3390/polym14102010.
Widyananda, M.H., Puspitarini, S., Rohim, A., Khairunnisa, F.A., Jatmiko, Y.D., Masruri, M., and Widodo, N., 2022. Anticancer Potential of Turmeric (Curcuma longa) Ethanol Extract and Prediction of Its Mechanism through the Akt1 Pathway. F1000Research, 11, 1000. https://doi.org/10.12688/f1000research.75735.1.
Wijayanti, P.A., Puspaningtyas, A.R., and Pangaribowo, D.A., 2015. Uji Sitotoksisitas dan Proliferasi Senyawa 1-(4-Trifluorometilbenzoiloksimetil)-5-Fluorourasil terhadap Sel Kanker Payudara MCF-7. e-Jurnal Pustaka Kesehatan, 3, 419–423.
World Cancer Research Fund, 2024. Breast cancer statistics. https://www.wcrf.org/preventing-cancer/cancer-statistics/breast-cancer-statistics/ (diakses pada 1 November 2024).
Yeo, S., Kim, M.J., Shim, Y.K., Yoon, I., and Lee, W.K., 2022. Solid Lipid Nanoparticles of Curcumin Designed for Enhanced Bioavailability and Anticancer Efficiency. ACS Omega, 7, 35875–35884. https://doi.org/10.1021/acsomega.2c04407.
Zhao, Q., Fan, L., Liu, Y., and Li, J., 2022. Recent Advances on Formation Mechanism and Functionality of Chitosan-Based Conjugates and Their Application in o/w Emulsion Systems: A Review. Food Chemistry, 380, 131838. https://doi.org/10.1016/j.foodchem.2021.131838.
Zoe, L.H., David, S.R., and Rajabalaya, R., 2023. Chitosan Nanoparticle Toxicity: A Comprehensive Literature Review of in Vivo and in Vitro Assessments for Medical Applications. Toxicology Reports, 11, 83–106. https://doi.org/10.1016/j.toxrep.2023.06.012.
Zu, Y., Zhao, Q., Zhao, X., Zu, S., and Meng, L., 2011. Process Optimization for the Preparation of Oligomycin-Loaded Folate-Conjugated Chitosan Nanoparticles as a Tumor-Targeted Drug Delivery System Using a Two-Level Factorial Design Method. International journal of nanomedicine, 6, 3429–3411. https://doi.org/10.2147/ijn.s27157.
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