Novel Self-Nanoemulsifying Drug Delivery System of Single Bulb Garlic: Stability, Toxicity, and Antiinflammation in 3T3-L1 Cells
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Keywords:
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Single bulb garlic, SNEDDS, 3T3-L1 line cells, TNF-????, IL-1�, IL 10
Abstract
Single bulb garlic (SBG) has the potential as an immunomodulator; however, it has low solubility and bioavailability. A lipid-based delivery system, that is, the self-nanoemulsifying drug delivery system (SNEDDS), offers a novel opportunity in drug delivery. SBG can be a suitable candidate for SNEDDS development. This research aims to describe the physical stability, toxicity test of the SNEDDS, and SNEDDS SBG potential as antiinflammation in 3T3-L1 cells. The SNEDDS is made with various ratios of concentrations of carrier oil, surfactants, and cosurfactants, namely, 0.50: 3.45: 0.96, and added with SBG extract (SBGE) of 20 mg/mL. The results of the response test of SNEDDS SBGE formulation indicate an average and standard deviation of emulsification time of 16.38±3.01 (second), pH 7.21±0.08, and transmittance of 98.40±0.23(%). The average nanoemulsion size is 14.333±0.416 nm, polydispersion index of 0.213±0.056, and zeta potential of -14.67±0.72 mV. The results of the physical stability test indicate no segregation, deposition, cracking, or creaming in all nanoemulsion samples and SNEDDS SBG. The MTT test in a dose of 62.5, 125, 250, 500, 100, 2000, and 4000 µg/mL suggests that the highest viability of the 3T3-L1 cells is at a dose of 2000 µg/mL, which is 97.83%±1.55%. Therefore, SNEDDS SBGE can be a potential candidate for oral preparation by increasing bioavailability and reducing toxicity in the 3T3-L1 cells. An antiinflammatory test on the TNF-???? and IL-1???? expressions influences the 3T3-L1 cells. the SNEDDS of SBGE has the potential to reduce the expression of TNF-???? and IL-1???? and increase IL-10 expression in the methylglyoxal-induced 3T3-L1 cells.
References
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Borlinghaus, J., Albrecht, F., Gruhlke, M. C. H., Nwachukwu, I. D., & Slusarenko, A. J. (2014). Allicin: Chemistry and biological properties. Molecules, 19(8), 12591–12618. https://doi.org/10.3390/molecules190812591.
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Ghosha, C., Yanga, S. H., Kim, J. G., Jeon, T. Il, Yoon, B. H., Lee, J. Y., … Hwang, S. G. (2013). Zinc-chelated vitamin C stimulates adipogenesis of 3T3-L1 cells. Asian-Australasian Journal of Animal Sciences, 26(8), 1189–1196. https://doi.org/10.5713/ajas.2013.13179.
Izham, M. N. M., Hussin, Y., Aziz, M. N. M., Yeap, S. K., Rahman, H. S., Masarudin, M. J., … Alitheen, N. B. (2019). Preparation and characterization of self nano-emulsifying drug delivery system loaded with citraland its antiproliferative effect on colorectal cells in vitro. Nanomaterials, 9(7). https://doi.org/10.3390/nano9071028.
Kany, S., Vollrath, J. T., & Relja, B. (2019). Cytokines in inflammatory disease 炎症性疾患におけるサイトカイン. International Journal of Molecular Sciences, 20(23), 1–31.
Kazi, M., Al-swairi, M., Ahmad, A., & Raish, M. (2019). Evaluation of Self-Nanoemulsifying Drug Delivery Systems ( SNEDDS ) for Poorly Water-Soluble Talinolol : Preparation , in vitro and in vivo Assessment. 10(May), 1–13. https://doi.org/10.3389/fphar.2019.00459.
Kazi, M., Nasr, F. A., Noman, O., Alharbi, A., Alqahtani, M. S., & Alanazi, F. K. (2020). Development, characterization optimization, and assessment of curcumin-loaded bioactive self-nanoemulsifying formulations and their inhibitory effects on human breast cancer MCF-7 cells. Pharmaceutics, 12(11), 1–19. https://doi.org/10.3390/pharmaceutics12111107.
Kovvasu, S. P., Kunamaneni, P., Joshi, R., & Betageri, G. V. (2019). Self-emulsifying Drug Delivery Systems and their Marketed Products: A review. Asian Journal of Pharmaceutics, 13(2), 73–84.
Le Lay, S., Simard, G., Martinez, M. C., & Andriantsitohaina, R. (2014). Oxidative stress and metabolic pathologies: From an adipocentric point of view. Oxidative Medicine and Cellular Longevity, 2014. https://doi.org/10.1155/2014/908539.
Lee, J. Y., & Gao, Y. (2012). Review of the Application of Garlic, Allium sativum, in Aquaculture. Journal of the World Aquaculture Society, 43(4), 447–458. https://doi.org/10.1111/j.1749-7345.2012.00581.x.
Lin, L., Allemekinders, H., Dansby, A., Campbell, L., Durance-Tod, S., Berger, A., & Jones, P. J. (2013). Evidence of health benefits of canola oil. Nutrition Reviews, 71(6), 370–385. https://doi.org/10.1111/nure.12033.
Loganes, C., Ballali, S., & Minto, C. (2016). Main Properties of Canola Oil Components: A Descriptive Review of Current Knowledge. The Open Agriculture Journal, 10(1), 69–74. https://doi.org/10.2174/1874331501610010069.
Martínez, M., Blanco, J., Rovira, J., Kumar, V., Domingo, J. L., & Schuhmacher, M. (2020). Bisphenol A analogues (BPS and BPF) present a greater obesogenic capacity in 3T3-L1 cell line. Food and Chemical Toxicology, 140(February), 111298. https://doi.org/10.1016/j.fct.2020.111298.
Matafome, P., Sena, C., & Seiça, R. (2013). Methylglyoxal, obesity, and diabetes. Endocrine, 43(3), 472–484. https://doi.org/10.1007/s12020-012-9795-8.
Mehmood, T. (2015). Optimization of the canola oil based vitamin E nanoemulsions stabilized by food grade mixed surfactants using response surface methodology. Food Chemistry, 183, 1–7. https://doi.org/10.1016/j.foodchem.2015.03.021.
Park, E. J., Lee, J. H., Yu, G. Y., He, G., Ali, S. R., Holzer, R. G., … Karin, M. (2010). Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression. Cell, 140(2), 197–208. https://doi.org/10.1016/j.cell.2009.12.052.
Patel, J., Patel, A., Raval, M., & Sheth, N. (2011). Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan. Journal of Advanced Pharmaceutical Technology and Research, 2(1), 9–16. https://doi.org/10.4103/2231-4040.79799.
Pratiwi, L., Fudholi, A., Martien, R., & Pramono, S. (2018). Uji Stabilitas Fisik dan Kimia Sediaan SNEDDS (Self-nanoemulsifying Drug Delivery System) dan Nanoemulsi Fraksi Etil Asetat Kulit Manggis (Garcinia mangostana L.) Physical and Chemical Stability Test of SNEDDS (Self-nanoemulsifying Drug Delivery System) a. Traditional Medicine Journal, 23(2), 84–90.
Priani, S. E., Nurrayyan, N., & Darusman, F. (2017). Formulation self nano emulsifying drug delivery system glimepiride using oleic acid as oil phase. Pharmaciana, 7(2), 267. https://doi.org/10.12928/pharmaciana.v7i2.7387.
Priani, S. E., Somantri, S. Y., & Aryani, R. (2020). Formulasi dan Karakterisasi SNEDDS (Self Nanoemulsifying Drug Delivery System) Mengandung Minyak Jintan Hitam dan Minyak Zaitun. Jurnal Sains Farmasi & Klinis, 7(1), 31. https://doi.org/10.25077/jsfk.7.1.31-38.2020.
Ragavan, G., Muralidaran, Y., Sridharan, B., Nachiappa Ganesh, R., & Viswanathan, P. (2017). Evaluation of garlic oil in nano-emulsified form: Optimization and its efficacy in high-fat diet induced dyslipidemia in Wistar rats. Food and Chemical Toxicology, 105, 203–213. https://doi.org/10.1016/j.fct.2017.04.019.
Ried, K., & Fakler, P. (2014). Potential of garlic (Allium sativum) in lowering high blood pressure: Mechanisms of action and clinical relevance. Integrated Blood Pressure Control, 7, 71–82. https://doi.org/10.2147/IBPC.S51434.
Singh, P., Singh, J., Singh, S., & Singh, B. . (2014). Medicinal values of Garlic (Allium sativum L.) in Human Life: An Overview. Greener Journal of Agricultural Sciences, 4(6), 265–280. https://doi.org/10.15580/gjas.2014.6.031914151.
Song, R., Yan, F., Cheng, M., Dong, F., Lin, Y., Wang, Y., & Song, B. (2020). Ultrasound-assisted preparation of exopolysaccharide/nystatin nanoemulsion for treatment of vulvovaginal candidiasis. International Journal of Nanomedicine, 15, 2027–2044. https://doi.org/10.2147/IJN.S241134.
Tran, T. H., Guo, Y., Song, D., Bruno, R. S., & Lu, X. (2014). Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. Journal of Pharmaceutical Sciences, 103(3), 840–852. https://doi.org/10.1002/jps.23858.
Ujilestari, T., Danar Dono, N., Ariyadi, B., Martien, R., & Zuprizal, Z. (2018). Formulation and characterization of self-nano emulsifying drug delivery systems of lemongrass (cymbopogon citratus) essential oil. Malaysian Journal of Fundamental and Applied Sciences, 14(3), 360–363. https://doi.org/10.11113/mjfas.v14n3.1070.
Ujilestari, T., Danar, N., Ariyadi, B., & Martien, R. (2018). Formulation and characterization of self-nano emulsifying drug delivery systems of lemongrass ( cymbopogon citratus ) essential oil. 14, 360–363.
Ujilestari, T., Martien, R., Ariyadi, B., Dono, N. D., & Zuprizal. (2018). Self-nanoemulsifying drug delivery system (SNEDDS) of Amomum compactum essential oil: Design, formulation, and characterization. Journal of Applied Pharmaceutical Science, 8(6), 14–21. https://doi.org/10.7324/JAPS.2018.8603.
Vulesevic, B., McNeill, B., Giacco, F., Maeda, K., Blackburn, N. J. R., Brownlee, M., … Suuronen, E. J. (2016). Methylglyoxal-induced endothelial cell loss and inflammation contribute to the development of diabetic cardiomyopathy. Diabetes, 65(6), 1699–1713. https://doi.org/10.2337/db15-0568.
Wang, Y., Hall, L. M., Kujawa, M., Li, H., Zhang, X., O’meara, M., … Wang, J. M. (2019). Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the kATP/MAPK pathway. American Journal of Physiology - Cell Physiology, 317(1), C68–C81. https://doi.org/10.1152/ajpcell.00117.2018.
Wulandari, E., Alverina, A., & Martien., R. (2016). SNEDDS (Sels-nanoemulsifiying Drug Delivery System) Formulation of β-carotene in Olive Oil (Olea europaea). International Journal of Advanced Research, 4(11), 1031–1043. https://doi.org/10.21474/ijar01/2179.
Yamawaki, H., Saito, K., Okada, M., & Hara, Y. (2008). Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells. American Journal of Physiology - Cell Physiology, 295(6), 1510–1517. https://doi.org/10.1152/ajpcell.00252.2008.
Yu, H., Li, R., Huang, H., Yao, R., & Shen, S. (2018). Short-Chain Fatty Acids Enhance the Lipid Accumulation of 3T3-L1 Cells by Modulating the Expression of Enzymes of Fatty Acid Metabolism. Lipids, 53(1), 77–84. https://doi.org/10.1002/lipd.12005.
Zhao, T., Maniglio, D., Chen, J., Chen, B., & Migliaresi, C. (2016). Development of pH-Sensitive Self-nanoemulsifying Drug Delivery Systems for Acid-labile Lipophilic Drugs. Chemistry and Physics of Lipids, 196, 81–88. https://doi.org/10.1016/j.chemphyslip.2016.02.008.
ZOTHANPUII, F., RAJESH, R., & SELVAKUMAR, K. (2020). a Review on Stability Testing Guidelines of Pharmaceutical Products. Asian Journal of Pharmaceutical and Clinical Research, (October), 3–9. https://doi.org/10.22159/ajpcr.2020.v13i10.38848.
Ambele, M. A., Dhanraj, P., Giles, R., & Pepper, M. S. (2020). Adipogenesis: A complex interplay of multiple molecular determinants and pathways. International Journal of Molecular Sciences, 21(12), 1–27. https://doi.org/10.3390/ijms21124283.
Baloch, J., Sohail, M. F., Sarwar, H. S., Kiani, M. H., Khan, G. M., Jahan, S., … Shahnaz, G. (2019). Self-nanoemulsifying drug delivery system (Snedds) for improved oral bioavailability of chlorpromazine: In vitro and in vivo evaluation. Medicina (Lithuania), 55(5), 1–13. https://doi.org/10.3390/medicina55050210.
Beandrade, M. U. (2018). Formulasi dan Karakterisasi SNEDDS Ekstrak Jinten Hitam (Nigella Sativa) dengan Fase Minyak Ikan Hiu Cucut Botol (Centrophorus Sp) serta Uji Aktivitas Imunostimulan. JPSCR : Journal of Pharmaceutical Science and Clinical Research, 3(1), 50. https://doi.org/10.20961/jpscr.v3i1.15506.
Birben, E., Sahiner, U. M., Sackesen, C., Erzurum, S., & Kalayci, O. (2012). Oxidative stress and antioxidant defense. World Allergy Organization Journal, 5(1), 9–19. https://doi.org/10.1097/WOX.0b013e3182439613.
Borlinghaus, J., Albrecht, F., Gruhlke, M. C. H., Nwachukwu, I. D., & Slusarenko, A. J. (2014). Allicin: Chemistry and biological properties. Molecules, 19(8), 12591–12618. https://doi.org/10.3390/molecules190812591.
Fernández-Sánchez, A., Madrigal-Santillán, E., Bautista, M., Esquivel-Soto, J., Morales-González, Á., Esquivel-Chirino, C., … Morales-González, J. A. (2011). Inflammation, oxidative stress, and obesity. International Journal of Molecular Sciences, 12(5), 3117–3132. https://doi.org/10.3390/ijms12053117.
Fitriana, N., Ainayya, A. A., Pamasyah, F. A., Anam, M. A., & Lestari, S. R. (2019). The Effectiveness Comparison of Single Bulb Garlic Extract for Antibacterial Agent P. aeruginosa. IOP Conference Series: Earth and Environmental Science, 276(1). https://doi.org/10.1088/1755-1315/276/1/012028.
Garlanda, C., Dinarello, C. A., & Mantovani, A. (2013). The Interleukin-1 Family: Back to the Future. Immunity, 39(6), 1003–1018. https://doi.org/10.1016/j.immuni.2013.11.010.
Ghosha, C., Yanga, S. H., Kim, J. G., Jeon, T. Il, Yoon, B. H., Lee, J. Y., … Hwang, S. G. (2013). Zinc-chelated vitamin C stimulates adipogenesis of 3T3-L1 cells. Asian-Australasian Journal of Animal Sciences, 26(8), 1189–1196. https://doi.org/10.5713/ajas.2013.13179.
Izham, M. N. M., Hussin, Y., Aziz, M. N. M., Yeap, S. K., Rahman, H. S., Masarudin, M. J., … Alitheen, N. B. (2019). Preparation and characterization of self nano-emulsifying drug delivery system loaded with citraland its antiproliferative effect on colorectal cells in vitro. Nanomaterials, 9(7). https://doi.org/10.3390/nano9071028.
Kany, S., Vollrath, J. T., & Relja, B. (2019). Cytokines in inflammatory disease 炎症性疾患におけるサイトカイン. International Journal of Molecular Sciences, 20(23), 1–31.
Kazi, M., Al-swairi, M., Ahmad, A., & Raish, M. (2019). Evaluation of Self-Nanoemulsifying Drug Delivery Systems ( SNEDDS ) for Poorly Water-Soluble Talinolol : Preparation , in vitro and in vivo Assessment. 10(May), 1–13. https://doi.org/10.3389/fphar.2019.00459.
Kazi, M., Nasr, F. A., Noman, O., Alharbi, A., Alqahtani, M. S., & Alanazi, F. K. (2020). Development, characterization optimization, and assessment of curcumin-loaded bioactive self-nanoemulsifying formulations and their inhibitory effects on human breast cancer MCF-7 cells. Pharmaceutics, 12(11), 1–19. https://doi.org/10.3390/pharmaceutics12111107.
Kovvasu, S. P., Kunamaneni, P., Joshi, R., & Betageri, G. V. (2019). Self-emulsifying Drug Delivery Systems and their Marketed Products: A review. Asian Journal of Pharmaceutics, 13(2), 73–84.
Le Lay, S., Simard, G., Martinez, M. C., & Andriantsitohaina, R. (2014). Oxidative stress and metabolic pathologies: From an adipocentric point of view. Oxidative Medicine and Cellular Longevity, 2014. https://doi.org/10.1155/2014/908539.
Lee, J. Y., & Gao, Y. (2012). Review of the Application of Garlic, Allium sativum, in Aquaculture. Journal of the World Aquaculture Society, 43(4), 447–458. https://doi.org/10.1111/j.1749-7345.2012.00581.x.
Lin, L., Allemekinders, H., Dansby, A., Campbell, L., Durance-Tod, S., Berger, A., & Jones, P. J. (2013). Evidence of health benefits of canola oil. Nutrition Reviews, 71(6), 370–385. https://doi.org/10.1111/nure.12033.
Loganes, C., Ballali, S., & Minto, C. (2016). Main Properties of Canola Oil Components: A Descriptive Review of Current Knowledge. The Open Agriculture Journal, 10(1), 69–74. https://doi.org/10.2174/1874331501610010069.
Martínez, M., Blanco, J., Rovira, J., Kumar, V., Domingo, J. L., & Schuhmacher, M. (2020). Bisphenol A analogues (BPS and BPF) present a greater obesogenic capacity in 3T3-L1 cell line. Food and Chemical Toxicology, 140(February), 111298. https://doi.org/10.1016/j.fct.2020.111298.
Matafome, P., Sena, C., & Seiça, R. (2013). Methylglyoxal, obesity, and diabetes. Endocrine, 43(3), 472–484. https://doi.org/10.1007/s12020-012-9795-8.
Mehmood, T. (2015). Optimization of the canola oil based vitamin E nanoemulsions stabilized by food grade mixed surfactants using response surface methodology. Food Chemistry, 183, 1–7. https://doi.org/10.1016/j.foodchem.2015.03.021.
Park, E. J., Lee, J. H., Yu, G. Y., He, G., Ali, S. R., Holzer, R. G., … Karin, M. (2010). Dietary and Genetic Obesity Promote Liver Inflammation and Tumorigenesis by Enhancing IL-6 and TNF Expression. Cell, 140(2), 197–208. https://doi.org/10.1016/j.cell.2009.12.052.
Patel, J., Patel, A., Raval, M., & Sheth, N. (2011). Formulation and development of a self-nanoemulsifying drug delivery system of irbesartan. Journal of Advanced Pharmaceutical Technology and Research, 2(1), 9–16. https://doi.org/10.4103/2231-4040.79799.
Pratiwi, L., Fudholi, A., Martien, R., & Pramono, S. (2018). Uji Stabilitas Fisik dan Kimia Sediaan SNEDDS (Self-nanoemulsifying Drug Delivery System) dan Nanoemulsi Fraksi Etil Asetat Kulit Manggis (Garcinia mangostana L.) Physical and Chemical Stability Test of SNEDDS (Self-nanoemulsifying Drug Delivery System) a. Traditional Medicine Journal, 23(2), 84–90.
Priani, S. E., Nurrayyan, N., & Darusman, F. (2017). Formulation self nano emulsifying drug delivery system glimepiride using oleic acid as oil phase. Pharmaciana, 7(2), 267. https://doi.org/10.12928/pharmaciana.v7i2.7387.
Priani, S. E., Somantri, S. Y., & Aryani, R. (2020). Formulasi dan Karakterisasi SNEDDS (Self Nanoemulsifying Drug Delivery System) Mengandung Minyak Jintan Hitam dan Minyak Zaitun. Jurnal Sains Farmasi & Klinis, 7(1), 31. https://doi.org/10.25077/jsfk.7.1.31-38.2020.
Ragavan, G., Muralidaran, Y., Sridharan, B., Nachiappa Ganesh, R., & Viswanathan, P. (2017). Evaluation of garlic oil in nano-emulsified form: Optimization and its efficacy in high-fat diet induced dyslipidemia in Wistar rats. Food and Chemical Toxicology, 105, 203–213. https://doi.org/10.1016/j.fct.2017.04.019.
Ried, K., & Fakler, P. (2014). Potential of garlic (Allium sativum) in lowering high blood pressure: Mechanisms of action and clinical relevance. Integrated Blood Pressure Control, 7, 71–82. https://doi.org/10.2147/IBPC.S51434.
Singh, P., Singh, J., Singh, S., & Singh, B. . (2014). Medicinal values of Garlic (Allium sativum L.) in Human Life: An Overview. Greener Journal of Agricultural Sciences, 4(6), 265–280. https://doi.org/10.15580/gjas.2014.6.031914151.
Song, R., Yan, F., Cheng, M., Dong, F., Lin, Y., Wang, Y., & Song, B. (2020). Ultrasound-assisted preparation of exopolysaccharide/nystatin nanoemulsion for treatment of vulvovaginal candidiasis. International Journal of Nanomedicine, 15, 2027–2044. https://doi.org/10.2147/IJN.S241134.
Tran, T. H., Guo, Y., Song, D., Bruno, R. S., & Lu, X. (2014). Quercetin-containing self-nanoemulsifying drug delivery system for improving oral bioavailability. Journal of Pharmaceutical Sciences, 103(3), 840–852. https://doi.org/10.1002/jps.23858.
Ujilestari, T., Danar Dono, N., Ariyadi, B., Martien, R., & Zuprizal, Z. (2018). Formulation and characterization of self-nano emulsifying drug delivery systems of lemongrass (cymbopogon citratus) essential oil. Malaysian Journal of Fundamental and Applied Sciences, 14(3), 360–363. https://doi.org/10.11113/mjfas.v14n3.1070.
Ujilestari, T., Danar, N., Ariyadi, B., & Martien, R. (2018). Formulation and characterization of self-nano emulsifying drug delivery systems of lemongrass ( cymbopogon citratus ) essential oil. 14, 360–363.
Ujilestari, T., Martien, R., Ariyadi, B., Dono, N. D., & Zuprizal. (2018). Self-nanoemulsifying drug delivery system (SNEDDS) of Amomum compactum essential oil: Design, formulation, and characterization. Journal of Applied Pharmaceutical Science, 8(6), 14–21. https://doi.org/10.7324/JAPS.2018.8603.
Vulesevic, B., McNeill, B., Giacco, F., Maeda, K., Blackburn, N. J. R., Brownlee, M., … Suuronen, E. J. (2016). Methylglyoxal-induced endothelial cell loss and inflammation contribute to the development of diabetic cardiomyopathy. Diabetes, 65(6), 1699–1713. https://doi.org/10.2337/db15-0568.
Wang, Y., Hall, L. M., Kujawa, M., Li, H., Zhang, X., O’meara, M., … Wang, J. M. (2019). Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the kATP/MAPK pathway. American Journal of Physiology - Cell Physiology, 317(1), C68–C81. https://doi.org/10.1152/ajpcell.00117.2018.
Wulandari, E., Alverina, A., & Martien., R. (2016). SNEDDS (Sels-nanoemulsifiying Drug Delivery System) Formulation of β-carotene in Olive Oil (Olea europaea). International Journal of Advanced Research, 4(11), 1031–1043. https://doi.org/10.21474/ijar01/2179.
Yamawaki, H., Saito, K., Okada, M., & Hara, Y. (2008). Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells. American Journal of Physiology - Cell Physiology, 295(6), 1510–1517. https://doi.org/10.1152/ajpcell.00252.2008.
Yu, H., Li, R., Huang, H., Yao, R., & Shen, S. (2018). Short-Chain Fatty Acids Enhance the Lipid Accumulation of 3T3-L1 Cells by Modulating the Expression of Enzymes of Fatty Acid Metabolism. Lipids, 53(1), 77–84. https://doi.org/10.1002/lipd.12005.
Zhao, T., Maniglio, D., Chen, J., Chen, B., & Migliaresi, C. (2016). Development of pH-Sensitive Self-nanoemulsifying Drug Delivery Systems for Acid-labile Lipophilic Drugs. Chemistry and Physics of Lipids, 196, 81–88. https://doi.org/10.1016/j.chemphyslip.2016.02.008.
ZOTHANPUII, F., RAJESH, R., & SELVAKUMAR, K. (2020). a Review on Stability Testing Guidelines of Pharmaceutical Products. Asian Journal of Pharmaceutical and Clinical Research, (October), 3–9. https://doi.org/10.22159/ajpcr.2020.v13i10.38848.
Authors
Miasih, D. S., Annisa, Y., Lestari, S. R., Susanto, H., & Sunaryono. (2022). Novel Self-Nanoemulsifying Drug Delivery System of Single Bulb Garlic: Stability, Toxicity, and Antiinflammation in 3T3-L1 Cells. Science and Technology Indonesia, 7(4), 417–426. https://doi.org/10.26554/sti.2022.7.4.417-426
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