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Saltwater Fish Nanoparticles: Biological Effects on COL1A1 Expression in Fetal Mice and Tablet Formula Optimization
Corresponding Author(s) : Sandy Christiono
Jurnal Ilmiah Perikanan dan Kelautan, 2025: IN PRESS ISSUE (JUST ACCEPTED MANUSCRIPT, 2025)
Abstract
Graphical Abstract
Highlight Research
- Saltwater fish Nano powder modulates the expression of matrix proteins, influencing early dental tissue development.
- Administration significantly decreases COL1A1 expression in fetal mouse teeth, affecting biomineralization.
- Increasing talc concentration improves flowability and formulation stability by reducing angle of repose, Carr’s index, and Hausner ratio.
- Findings suggest marine-derived nanoparticles regulate cellular differentiation during dental development.
- Supports potential applications of marine natural materials in prenatal nutrition and dental tissue engineering.
Abstract
Saltwater fish nanoparticle-based tablets represent a novel nutritional strategy aimed enhancing dental hard tissue density, particularly enamel. These tablets incorporate bioactive proteins, omega-3 fatty acids, and essential minerals such as calcium, phosphate, and magnesium to support enamel biomineralization. The nanoparticle formulation facilitates efficient cellular absorption, thereby increasing the expression of key enamel proteins like collagen type I alpha 1 chain (COL1A1) during enamel matrix development. This study investigated the effect of saltwater fish nanoparticles on COL1A1 expression in ameloblast cells and evaluated the physicochemical properties of tablets with talc concentrations of 1%, 5%, and 10%. Using a true experimental design with a post-test only control group, two groups of mice were assigned: a control group fed standard diet, and a treatment group fed a standard diet supplemented with saltwater fish nanoparticles (2.17 mg/0.5 mL). Tablet formulations were analyzed across the three talc concentrations. Data were subjected to independent T-tests for COL1A1 expression and One-way ANOVA for physicochemical properties. Results revealed a significant reduction in COL1A1 expression in the treatment group. Additionally, talc concentration significantly influenced tablet physicochemical characteristics, with the 10% talc formulation exhibiting the most optimal properties. These findings suggest potential for nanoparticle-based nutritional interventions to promote enamel formation.
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- Apeji, Y. E., & Olowosulu, A. K. (2020). Quantifying the effect of glidant on the compaction and tableting properties of paracetamol granules. Journal of Research in Pharmacy, 24(1):44-55.
- Assaraf-Weill, N., Gasse, B., Silvent, J., Bardet, C., Sire, J. Y., & Davit-Béal, T. (2014). Ameloblasts express type I collagen during amelogenesis. Journal of Dental Research, 93(5):502-507.
- Braut, A., Kollar, E. J., & Mina, M. (2003). Analysis of the odontogenic and osteogenic potentials of dental pulp in vivo using a Colla1-2.3-GFP transgene. International Journal of Developmental Biology, 47(4):281-292.
- Champilomati, A. P., & Makedos, P. I. (2025). Maternal vitamin D levels during pregnancy and its effects on enamel dental defects of their children. A literature review. International Journal Dental and Medical Sciences Research, 7(1):349-355.
- Chendo, C., Pinto, J. F., & Paisana, M. C. (2023). Comprehensive powder flow characterization with reduced testing. International Journal of Pharmaceutics, 642(13):1-12.
- Christiono, S., Ardiani, F. P., Anggarani, W., & Eljabbar, F. D. (2021). The effect of saltwater fish nanoparticle powder consumption on tooth enamel density in vivo study of mice (Mus musculus). Dentino: Jurnal Kedokteran Gigi, 6(1):1-5.
- Christiono, S., Pradopo, S., Hutami, I. R., Indasari, N., Nurhapsari, A., Rochmah, Y. S. R., Ibrahim, Z., Yuniar, S. N., & Suparmi, S. (2024a). Saltwater fish powder for amelogenesis in zebrafish larvae (Danio rerio). Jurnal Ilmiah Perikanan Dan Kelautan, 16(2):510-518.
- Christiono, S., Pradopo, S., Pratama, M. D. P., Arbianti, K., Hutami, I. R., Mayangsari, R. S., Indrawati, S. V., & Ibrahim, Z. (2024b). The impact of nanoparticles saltwater fish on osteoblast cells during the alveolar bone formation stages in fetal mice. Journal of International Dental and Medical Research, 17(3):1112-1118.
- Christiono, S., Pradopo, S., & Sudiana, I. K. (2022). The effect of saltwater fish consumption by mother mice (Mus Musculus) on the expressions of FABPs and type 1 collagen regarding increase in enamel density. Journal of International Dental and Medical Research, 15(4):1535-1540.
- Christiono, S., Pradopo, S., Sudiana, I. K., Hutami, I. R., Mayangsari, R. S., Rochmah, Y. S., & Ibrahim, Z. (2023a). Amelogenin and alkaline phosphatase expression in ameloblast after saltwater fish consumption in pregnant mice (Mus musculus). Dental Journal, Majalah Kedokteran Gigi, 56(3):166-171.
- Christiono, S., Pradopo, S., Sudiana, I. K., Mayangsari, R. S., & Indrawati, S. V. (2023b). The effect of sea fish powder on development and growth of fetal teeth mice. Insisiva Dental Journal: Majalah Kedokteran Gigi Insisiva, 12(2):70-77.
- Christiono, S., Salsabila, N., Amalina, R., Anggarani, W., & Hutami, I. R. (2023c). The impact of consuming salmon fish (Salmo salar) on dental calcium levels in mice (Mus musculus). Dentino: Jurnal Kedokteran Gigi, 8(1):81-85.
- Collignon, A. M., Vergnes, J. N., Germa, A., Azogui, S., Breinig, S., Hollande, C., Bonnet, A. L., & Nabet, C. (2022). Factors and mechanisms involved in acquired developmental defects of enamel: A scoping review. Frontiers in Pediatrics, 10(1):1-13.
- Danaei, M., Dehghankhold, M., Ataei, S., Davarani, F. H., Javanmard, R., Dokhani, A., Khorasani, S., & Mozafari, M. R. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10(2):1-17.
- Dinesh, B. M., & Mutahar, R. K. M. (2009). Compatibility studies of intrinsic lubricants for effervescent tablets: Formulation and in vitro evaluation. Biomedical and Pharmacology Journal, 2(1):21-29.
- Eraga, S. O., Erebor, J. O., & Iwuagwu, M. A. (2015). A comparative study of the flow enhancing properties of bentonite, magnesium stearate, talc and microcrystalline cellulose. Journal of Pharmacy & Bioresources, 12(1):1-7.
- Fu, M., Blechar, J. A., Sauer, A., Al-Gousous, J., & Langguth, P. (2020). In vitro evaluation of enteric-coated HPMC capsules effect of formulation factors on product performance. Pharmaceutics, 12(8):1-17.
- Haripriyaa, M., & Suthindhiran, K. (2023). Pharmacokinetics of nanoparticles: Current knowledge, future directions and its implications in drug delivery. Future Journal of Pharmaceutical Sciences, 9(1):1-26.
- Honciuc, M., & Honciuc, A. (2024). Morphological design and synthesis of nanoparticles. Nanomaterials, 14(4):1-5.
- Hou, L., Lin, T., Wang, Y., Liu, B., & Wang, M. (2021). Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer. Journal of Cancer, 12(19):5723-5731.
- Kuno, Y., Kojima, M., Nakagami, H., Yonemochi, E., & Terada, K. (2008). Effect of the type of lubricant on the characteristics of orally disintegrating tablets manufactured using the phase transition of sugar alcohol. European Journal of Pharmaceutics and Biopharmaceutics, 69(3):986-992.
- Ma, X., Ma, Y., Lin, Z., & Ji, M. (2025). The role of the TGF-β1 signaling pathway in the process of amelogenesis. Frontiers in Physiology, 16(1):1-14.
- Mall, J., Naseem, N., Haider, M. F., Rahman, M. A., Khan, S., & Siddiqui, S. N. (2024). Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications. Intelligent Pharmacy. 3(4):243-255.
- Padmanaban, S., Baek, J. W., Chamarthy, S. S., Chandrasekaran, S., Samrot, A. V., Gosu, V., Park, I. K., Radhakrishnan, K., & Kim, D. K. (2025). Nanoparticle-based therapeutic strategies for chronic liver diseases: Advances and insights. Liver Research, 9(2):104-117.
- Patel, M., Patel, S., & Patel, N. (2009). flowability testing of directly compressible excipients according to British pharmacopoeia. Journal of Pharmaceutical Research, 8(2):79-85.
- Piekoszewska-Ziętek, P., Spodzieja, K., & Olczak-Kowalczyk, D. (2025). Influence of vitamin D on developmental defects of enamel (DDE) in children and adolescents: A systematic review. Nutrients, 17(8):1-14.
- Pitts, N. B., Zero, D. T., Marsh, P. D., Ekstrand, K., Weintraub, J. A., Ramos-Gomez, F., Tagami, J., Twetman, S., Tsakos, G., & Ismail, A. (2017). Dental caries. Nature Reviews Disease Primers, 3(1):1-7.
- Pushpalatha, C., Gayathri, V. S., Sowmya, S. V, Augustine, D., Alamoudi, A., Zidane, B., Albar, N. H. M., & Bhandi, S. (2023). Nanohydroxyapatite in dentistry: A comprehensive review. The Saudi Dental Journal, 35(6):741-752.
- Putri, W. A., Christiono, S., & Fathurrahman, H. (2021). The effect of consumption of marine fish nanoparticles on the hardness of teeth enamel in mice (Mus musculus). Jurnal Kesehatan Gigi, 8(2):109-114.
- Rong, H., Zhang, H., Ning, L., Wu, K., Limbu, S. M., Shi, Q., Qin, C., & Wen, X. (2022). The transforming growth factor beta (TGF-β/Smads) pathway regulates collagen synthesis and deposition in swim bladder of Chu’s croaker (Nibea coibor) stimulated by proline. Aquaculture, 558(14):1-11.
- Rosowski, J., Bräunig, J., Amler, A. K., Strietzel, F. P., Lauster, R., & Rosowski, M. (2019). Emulating the early phases of human tooth development in vitro. Scientific Reports, 9(1):1-14.
- Said, R., Lobanova, L., Papagerakis, S., & Papagerakis, P. (2020). Calcium sets the clock in ameloblasts. Frontiers in Physiology, 11(1):1-10.
- Shah, H., Jain, A., Laghate, G., & Prabhudesai, D. (2021). Chapter 32 - Pharmaceutical excipients. In A. Adejare (Ed.), Remington (Twenty-third Edition) (pp. 633-643). Academic Press.
- Sitosari, H., Sari, F. T., Jonarta, A., & Haniastuti, T. (2020a). Consumption of nano calcium and vitamin D affects the day of eruption and eruption level of Sprague Dawley Maxillary and Mandibular Incisors. Malaysian Journal of Medicine and Health Sciences, 16(15):67-72.
- Sitosari, H., Sari, F. T., Jonarta, A., & Haniastuti, T. (2020b). Consumption of nano calcium and vitamin D affects the day of eruption and eruption level of Sprague Dawley Maxillary and Mandibular Incisors. Malaysian Journal of Medicine & Health Sciences, 16(15):2636-9346.
- Teti, G., Salvatore, V., Ruggeri, A., Manzoli, L., Gesi, M., Orsini, G., & Falconi, M. (2013). In vitro reparative dentin: A biochemical and morphological study. European Journal of Histochemistry, 57(3):151-158.
- Varia, U., Patel, A., Katariya, H., & Detholia, K. (2022). Formulation and optimization of polymeric agglomerates of bosentan monohydrate by crystallo-co-agglomeration technique. Bulletin of the National Research Centre, 46(1):1-13.
- Xing, H., Yang, F., Sun, S., Pan, P., Wang, H., Wang, Y., & Chen, J. (2022). Green efficient ultrasonic-assisted extraction of abalone nacre water-soluble organic matrix for bioinspired enamel remineralization. Colloids and Surfaces B: Biointerfaces, 212(5):1-10.
- Zhang, W., Taheri-Ledari, R., Ganjali, F., Mirmohammadi, S. S., Qazi, F. S., Saeidirad, M., KashtiAray, A., Zarei-Shokat, S., Tian, Y., & Maleki, A. (2022). Effects of morphology and size of nanoscale drug carriers on cellular uptake and internalization process: A review. RSC Advances, 13(2):1-35.
- Zhao, H., Yu, Y., Ni, N., Zhao, L., Lin, X., Wang, Y., Du, R., & Shen, L. (2022). A new parameter for characterization of tablet friability based on a systematical study of five excipients. International Journal of Pharmaceutics, 611(1):1-11.
References
Apeji, Y. E., & Olowosulu, A. K. (2020). Quantifying the effect of glidant on the compaction and tableting properties of paracetamol granules. Journal of Research in Pharmacy, 24(1):44-55.
Assaraf-Weill, N., Gasse, B., Silvent, J., Bardet, C., Sire, J. Y., & Davit-Béal, T. (2014). Ameloblasts express type I collagen during amelogenesis. Journal of Dental Research, 93(5):502-507.
Braut, A., Kollar, E. J., & Mina, M. (2003). Analysis of the odontogenic and osteogenic potentials of dental pulp in vivo using a Colla1-2.3-GFP transgene. International Journal of Developmental Biology, 47(4):281-292.
Champilomati, A. P., & Makedos, P. I. (2025). Maternal vitamin D levels during pregnancy and its effects on enamel dental defects of their children. A literature review. International Journal Dental and Medical Sciences Research, 7(1):349-355.
Chendo, C., Pinto, J. F., & Paisana, M. C. (2023). Comprehensive powder flow characterization with reduced testing. International Journal of Pharmaceutics, 642(13):1-12.
Christiono, S., Ardiani, F. P., Anggarani, W., & Eljabbar, F. D. (2021). The effect of saltwater fish nanoparticle powder consumption on tooth enamel density in vivo study of mice (Mus musculus). Dentino: Jurnal Kedokteran Gigi, 6(1):1-5.
Christiono, S., Pradopo, S., Hutami, I. R., Indasari, N., Nurhapsari, A., Rochmah, Y. S. R., Ibrahim, Z., Yuniar, S. N., & Suparmi, S. (2024a). Saltwater fish powder for amelogenesis in zebrafish larvae (Danio rerio). Jurnal Ilmiah Perikanan Dan Kelautan, 16(2):510-518.
Christiono, S., Pradopo, S., Pratama, M. D. P., Arbianti, K., Hutami, I. R., Mayangsari, R. S., Indrawati, S. V., & Ibrahim, Z. (2024b). The impact of nanoparticles saltwater fish on osteoblast cells during the alveolar bone formation stages in fetal mice. Journal of International Dental and Medical Research, 17(3):1112-1118.
Christiono, S., Pradopo, S., & Sudiana, I. K. (2022). The effect of saltwater fish consumption by mother mice (Mus Musculus) on the expressions of FABPs and type 1 collagen regarding increase in enamel density. Journal of International Dental and Medical Research, 15(4):1535-1540.
Christiono, S., Pradopo, S., Sudiana, I. K., Hutami, I. R., Mayangsari, R. S., Rochmah, Y. S., & Ibrahim, Z. (2023a). Amelogenin and alkaline phosphatase expression in ameloblast after saltwater fish consumption in pregnant mice (Mus musculus). Dental Journal, Majalah Kedokteran Gigi, 56(3):166-171.
Christiono, S., Pradopo, S., Sudiana, I. K., Mayangsari, R. S., & Indrawati, S. V. (2023b). The effect of sea fish powder on development and growth of fetal teeth mice. Insisiva Dental Journal: Majalah Kedokteran Gigi Insisiva, 12(2):70-77.
Christiono, S., Salsabila, N., Amalina, R., Anggarani, W., & Hutami, I. R. (2023c). The impact of consuming salmon fish (Salmo salar) on dental calcium levels in mice (Mus musculus). Dentino: Jurnal Kedokteran Gigi, 8(1):81-85.
Collignon, A. M., Vergnes, J. N., Germa, A., Azogui, S., Breinig, S., Hollande, C., Bonnet, A. L., & Nabet, C. (2022). Factors and mechanisms involved in acquired developmental defects of enamel: A scoping review. Frontiers in Pediatrics, 10(1):1-13.
Danaei, M., Dehghankhold, M., Ataei, S., Davarani, F. H., Javanmard, R., Dokhani, A., Khorasani, S., & Mozafari, M. R. (2018). Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics, 10(2):1-17.
Dinesh, B. M., & Mutahar, R. K. M. (2009). Compatibility studies of intrinsic lubricants for effervescent tablets: Formulation and in vitro evaluation. Biomedical and Pharmacology Journal, 2(1):21-29.
Eraga, S. O., Erebor, J. O., & Iwuagwu, M. A. (2015). A comparative study of the flow enhancing properties of bentonite, magnesium stearate, talc and microcrystalline cellulose. Journal of Pharmacy & Bioresources, 12(1):1-7.
Fu, M., Blechar, J. A., Sauer, A., Al-Gousous, J., & Langguth, P. (2020). In vitro evaluation of enteric-coated HPMC capsules effect of formulation factors on product performance. Pharmaceutics, 12(8):1-17.
Haripriyaa, M., & Suthindhiran, K. (2023). Pharmacokinetics of nanoparticles: Current knowledge, future directions and its implications in drug delivery. Future Journal of Pharmaceutical Sciences, 9(1):1-26.
Honciuc, M., & Honciuc, A. (2024). Morphological design and synthesis of nanoparticles. Nanomaterials, 14(4):1-5.
Hou, L., Lin, T., Wang, Y., Liu, B., & Wang, M. (2021). Collagen type 1 alpha 1 chain is a novel predictive biomarker of poor progression-free survival and chemoresistance in metastatic lung cancer. Journal of Cancer, 12(19):5723-5731.
Kuno, Y., Kojima, M., Nakagami, H., Yonemochi, E., & Terada, K. (2008). Effect of the type of lubricant on the characteristics of orally disintegrating tablets manufactured using the phase transition of sugar alcohol. European Journal of Pharmaceutics and Biopharmaceutics, 69(3):986-992.
Ma, X., Ma, Y., Lin, Z., & Ji, M. (2025). The role of the TGF-β1 signaling pathway in the process of amelogenesis. Frontiers in Physiology, 16(1):1-14.
Mall, J., Naseem, N., Haider, M. F., Rahman, M. A., Khan, S., & Siddiqui, S. N. (2024). Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications. Intelligent Pharmacy. 3(4):243-255.
Padmanaban, S., Baek, J. W., Chamarthy, S. S., Chandrasekaran, S., Samrot, A. V., Gosu, V., Park, I. K., Radhakrishnan, K., & Kim, D. K. (2025). Nanoparticle-based therapeutic strategies for chronic liver diseases: Advances and insights. Liver Research, 9(2):104-117.
Patel, M., Patel, S., & Patel, N. (2009). flowability testing of directly compressible excipients according to British pharmacopoeia. Journal of Pharmaceutical Research, 8(2):79-85.
Piekoszewska-Ziętek, P., Spodzieja, K., & Olczak-Kowalczyk, D. (2025). Influence of vitamin D on developmental defects of enamel (DDE) in children and adolescents: A systematic review. Nutrients, 17(8):1-14.
Pitts, N. B., Zero, D. T., Marsh, P. D., Ekstrand, K., Weintraub, J. A., Ramos-Gomez, F., Tagami, J., Twetman, S., Tsakos, G., & Ismail, A. (2017). Dental caries. Nature Reviews Disease Primers, 3(1):1-7.
Pushpalatha, C., Gayathri, V. S., Sowmya, S. V, Augustine, D., Alamoudi, A., Zidane, B., Albar, N. H. M., & Bhandi, S. (2023). Nanohydroxyapatite in dentistry: A comprehensive review. The Saudi Dental Journal, 35(6):741-752.
Putri, W. A., Christiono, S., & Fathurrahman, H. (2021). The effect of consumption of marine fish nanoparticles on the hardness of teeth enamel in mice (Mus musculus). Jurnal Kesehatan Gigi, 8(2):109-114.
Rong, H., Zhang, H., Ning, L., Wu, K., Limbu, S. M., Shi, Q., Qin, C., & Wen, X. (2022). The transforming growth factor beta (TGF-β/Smads) pathway regulates collagen synthesis and deposition in swim bladder of Chu’s croaker (Nibea coibor) stimulated by proline. Aquaculture, 558(14):1-11.
Rosowski, J., Bräunig, J., Amler, A. K., Strietzel, F. P., Lauster, R., & Rosowski, M. (2019). Emulating the early phases of human tooth development in vitro. Scientific Reports, 9(1):1-14.
Said, R., Lobanova, L., Papagerakis, S., & Papagerakis, P. (2020). Calcium sets the clock in ameloblasts. Frontiers in Physiology, 11(1):1-10.
Shah, H., Jain, A., Laghate, G., & Prabhudesai, D. (2021). Chapter 32 - Pharmaceutical excipients. In A. Adejare (Ed.), Remington (Twenty-third Edition) (pp. 633-643). Academic Press.
Sitosari, H., Sari, F. T., Jonarta, A., & Haniastuti, T. (2020a). Consumption of nano calcium and vitamin D affects the day of eruption and eruption level of Sprague Dawley Maxillary and Mandibular Incisors. Malaysian Journal of Medicine and Health Sciences, 16(15):67-72.
Sitosari, H., Sari, F. T., Jonarta, A., & Haniastuti, T. (2020b). Consumption of nano calcium and vitamin D affects the day of eruption and eruption level of Sprague Dawley Maxillary and Mandibular Incisors. Malaysian Journal of Medicine & Health Sciences, 16(15):2636-9346.
Teti, G., Salvatore, V., Ruggeri, A., Manzoli, L., Gesi, M., Orsini, G., & Falconi, M. (2013). In vitro reparative dentin: A biochemical and morphological study. European Journal of Histochemistry, 57(3):151-158.
Varia, U., Patel, A., Katariya, H., & Detholia, K. (2022). Formulation and optimization of polymeric agglomerates of bosentan monohydrate by crystallo-co-agglomeration technique. Bulletin of the National Research Centre, 46(1):1-13.
Xing, H., Yang, F., Sun, S., Pan, P., Wang, H., Wang, Y., & Chen, J. (2022). Green efficient ultrasonic-assisted extraction of abalone nacre water-soluble organic matrix for bioinspired enamel remineralization. Colloids and Surfaces B: Biointerfaces, 212(5):1-10.
Zhang, W., Taheri-Ledari, R., Ganjali, F., Mirmohammadi, S. S., Qazi, F. S., Saeidirad, M., KashtiAray, A., Zarei-Shokat, S., Tian, Y., & Maleki, A. (2022). Effects of morphology and size of nanoscale drug carriers on cellular uptake and internalization process: A review. RSC Advances, 13(2):1-35.
Zhao, H., Yu, Y., Ni, N., Zhao, L., Lin, X., Wang, Y., Du, R., & Shen, L. (2022). A new parameter for characterization of tablet friability based on a systematical study of five excipients. International Journal of Pharmaceutics, 611(1):1-11.