Surfactant Variations in Capsanthin-loaded Nanostructured Lipid Carrier: Formulation, Characterization, and Stability Study
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Keywords:
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Stability, Surfactant, Capsanthin, Nanostructured Lipid Carrier
Abstract
The stability of drugs and nanocarriers is a crucial factor in guaranteeing their efficacy and quality. Nanostructured lipid carriers (NLCs) as lipid-based nanocarriers provide benefits in overcoming the stability and other issues associated with the drug. Surfactants play a crucial role in imparting the desired characteristics of lipid based systems, including stability, particle size, size distribution, and zeta potential. This study aimed to develop a capsanthin-loaded NLC formulation with an optimal surfactant combination that exhibits the required properties and stability. Three formulations were prepared applying Tween 20 and Span 80 in ratios of 5:1, 2:1, and 1:1 for F1, F2, and F3, respectively. Capsanthin, as an active ingredient, originates from paprika powder. NLC properties regarding transmittance, particle size, polydispersity index (PI), zeta potential, loading capacity (LC), and loading efficiency (LE) were characterized. Furthermore, stability studies were also conducted in this research. The results showed that F1 exhibited desirable characteristics, including transmittance percentage, particle size, PI, zeta potential, LC, and LE of 87.22±2.64%, 255.4±46.88 nm, 0.54±0.13, -39.51±3.02 mV, 12.59±0.35%, and 35.40±3.07%, respectively. Moreover, the physical stability studies exhibited that F1 provided a more stable system compared to other formulations. Additionally, the chemical stability indicated that degradation occurred in the paprika powder, not in the NLC. In conclusion, NLC can protect capsanthin, as evidenced by the stable capsanthin levels in NLC compared to those in paprika powder.
References
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Khan, S., A. Sharma, and V. Jain (2023). An Overview of Nanostructured Lipid Carriers and Its Application in Drug Delivery Through Different Routes. Advanced Pharmaceutical Bulletin, 13(3); 446–460
Khan, S. A., S. B. Khan, L. U. Khan, A. Farooq, K. Akhtar, and A. M. Asiri (2018). Fourier Transform Infrared Spectroscopy: Fundamentals and Application in Functional Groups and Nanomaterials Characterization. In S. K. Sharma, editor, Handbook of Materials Characterization. Springer International Publishing, Cham, pages 317–344
Knoll, P., N. Hörmann, N.-M. Nguyen Le, R. Wibel, R. Gust, and A. Bernkop-Schnürch (2022). Charge Converting Nanostructured Lipid Carriers Containing a Cell-Penetrating Peptide for Enhanced Cellular Uptake. Journal of Colloid and Interface Science, 628; 463–475
Kulkarni, M., N. Goge, and A. A. Date (2020). Development of Nanoemulsion Preconcentrate of Capsanthin with Improved Chemical Stability. ASSAY and Drug Development Technologies, 18(1); 34–44
Lasoń, E., E. Sikora, and J. Ogonowski (2013). Influence of Process Parameters on Properties of Nanostructured Lipid Carriers (NLC) Formulation. Acta Biochimica Polonica, 60(4); 773–777
Liu,W.-Q., S.-Z. Yang, H.-Z. Gang, B.-Z. Mu, and J.-F. Liu (2020). Efficient Emulsifying Properties of Monoglycerides Synthesized via Simple and Green Route. Journal of Dispersion Science and Technology, 41(12); 1902–1910
Madaniyah, L., S. Fiddaroini, E. K. Hayati, M. F. Rahman, and A. Sabarudin (2025). Stability of Biologically Synthesized Silver Nanoparticles (AgNPs) Using Acalypha indica L. Plant Extract as Bioreductor and Their Potential as Anticancer Agents Against T47D Cells. Science and Technology Indonesia, 10(1); 101–110
Mahor, A. K., P. P. Singh, R. Gupta, P. Bhardwaj, P. Rathore, A. Kishore, and K. K. Bansal (2023). Nanostructured Lipid Carriers for Improved Delivery of Therapeutics via the Oral Route. Journal of Nanotechnology, 2023(1); 4687959
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Pink, D. L., O. Loruthai, R. M. Ziolek, A. E. Terry, D. J. Barlow, M. J. Lawrence, and C. D. Lorenz (2021). Interplay of Lipid and Surfactant: Impact on Nanoparticle Structure. Journal of Colloid and Interface Science, 597; 278–288
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Shevalkar, G. and P. Vavia (2019). Solidified Nanostructured Lipid Carrier (S-NLC) for Enhancing the Oral Bioavailability of Ezetimibe. Journal of Drug Delivery Science and Technology, 53; 101211
Smejkal, G., V. Gross, and A. Lazarev (2024). Theoretical and Experimental Determinations of theHydrophilic–Lipophilic Balance (HLB) of Representative Oils and Lecithins. Colloids and Interfaces, 8(2); 21
Subramaniam, B., Z. H. Siddik, and N. H. Nagoor (2020). Optimization of Nanostructured Lipid Carriers: Understanding the Types, Designs, and Parameters in the Process of Formulations. Journal of Nanoparticle Research, 22(6); 141
Varela-Fernández, R., X. García-Otero, V. Díaz-Tomé, U. Regueiro, M. López-López, M. González-Barcia, and F. J. Otero-Espinar (2022). Lactoferrin-Loaded Nanostructured Lipid Carriers (NLCs) as a New Formulation for Optimized Ocular Drug Delivery. European Journal of Pharmaceutics and Biopharmaceutics, 172; 144–156
Wang, Q., H. Zhang, Y. Han, Y. Cui, and X. Han (2023). Study on the Relationships Between the Oil HLB Value and Emulsion Stabilization. RSC Advances, 13(35); 24692–24698
Witayaudom, P. and U. Klinkesorn (2017). Effect of Surfactant Concentration and Solidification Temperature on the Characteristics and Stability of Nanostructured Lipid Carrier (NLC) Prepared from Rambutan (Nephelium lappaceum L.) Kernel Fat. Journal of Colloid and Interface Science, 505; 1082–1092
Yeo, S., M. J. Kim, Y. K. Shim, I. Yoon, and W. K. Lee (2022). Solid Lipid Nanoparticles of Curcumin Designed for Enhanced Bioavailability and Anticancer Efficiency. ACS Omega, 7(40); 35875–35884
Yousaf, R., M. I. Khan, M. F. Akhtar, A. Madni, M. F. Sohail, A. Saleem, and M. Rana (2023). Development and In-Vitro Evaluation of Chitosan and Glyceryl Monostearate Based Matrix Lipid Polymer Hybrid Nanoparticles (LPHNPs) for Oral Delivery of Itraconazole. Heliyon, 9(3); e14281
Yu, Y.-Q., X. Yang, X.-F. Wu, and Y.-B. Fan (2021). Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications. Frontiers in Bioengineering and Biotechnology, 9; 646554
Zhang, T., Q. Peng, Y. Xia, Y. Zhang, K. Z. Myint, and J.Wu (2021). Steviol Glycosides, an Edible Sweet Surfactant That Can Modulate the Interfacial and Emulsifying Properties of Soy Protein Isolate Solution. Journal of Food Engineering, 289; 110264
Zhu, Y., X. Liang, C. Lu, Y. Kong, X. Tang, Y. Zhang, and H. He (2020). Nanostructured Lipid Carriers as Oral Delivery Systems for Improving Oral Bioavailability of Nintedanib by Promoting Intestinal Absorption. International Journal of Pharmaceutics, 586; 119569
Baig, M. S. and A.-U.-R. Siddiqui (2020). Cationic Nanostructured Lipid Carriers: Optimization of Zeta Potential and Evaluation. International Journal of Applied Pharmaceutics, 12(4); 77–84
Bhalani, D. V., B. Nutan, A. Kumar, and A. K. Singh Chandel (2022). Bioavailability Enhancement Techniques for Poorly Aqueous Soluble Drugs and Therapeutics. Biomedicines, 10(9); 2055
Binarjo, A. and A. Nugroho (2019). Improvement of Losartan Transdermal Permeation Using Oleic Acid Pretreatment: In Vitro Observation and In Vivo Prediction. Pharmaceutical Sciences and Research, 6(1); 1–8
Bnyan, R., I. Khan, T. Ehtezazi, I. Saleem, S. Gordon, F. O’Neill, and M. Roberts (2018). Surfactant Effects on Lipid-Based Vesicles Properties. Journal of Pharmaceutical Sciences, 107(5); 1237–1246
Botto, C., N. Mauro, E. Amore, E. Martorana, G. Giammona, and M. L. Bondì (2017). Surfactant Effect on the Physicochemical Characteristics of Cationic Solid Lipid Nanoparticles. International Journal of Pharmaceutics, 516(1–2); 334–341
Chauhan, I., M. Yasir, M. Verma, and A. P. Singh (2020). Nanostructured Lipid Carriers: A Groundbreaking Approach for Transdermal Drug Delivery. Advanced Pharmaceutical Bulletin, 10(2); 150–165
Chenxi, Z., A. Hemmat, N. Thi, and M. Afrand (2025). Nanoparticle-Enhanced Drug Delivery Systems: An Upto-Date Review. Journal of Molecular Liquids, 424; 126999
Danaei, M., M. Dehghankhold, S. Ataei, F. HasanzadehDavarani, R. Javanmard, A. Dokhani, and M. R.Mozafari (2018). Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics, 10(2); 57
de Oliveira, G. L. R., I. Medeiros, S. S. d. C. Nascimento, R. L. S. Viana, D. L. Porto, H. A.O. Rocha, and T. S. Passos (2021). Antioxidant Stability Enhancement of Carotenoid-Rich Extract from Cantaloupe Melon (Cucumis melo L.) Nanoencapsulated in Gelatin Under Different Storage Conditions. Food Chemistry, 348; 129055
Dhiman, N., R. Awasthi, B. Sharma, H. Kharkwal, and G. T. Kulkarni (2021). Lipid Nanoparticles as Carriers for Bioactive Delivery. Frontiers in Chemistry, 9; 580118
Duong, V., T. Nguyen, H. Maeng, and S. Chi (2019). Preparation of Ondansetron Hydrochloride-Loaded Nanostructured Lipid Carriers Using Solvent Injection Method for Enhancement of Pharmacokinetic Properties. Pharmaceutical Research, 36(10); 138
Eh Suk, V. R., F.Mohd. Latif, Y. Y. Teo, and M. Misran (2020). Development of Nanostructured Lipid Carrier (NLC) Assisted with Polysorbate Nonionic Surfactants as a Carrier for L-Ascorbic Acid and Gold Tri.E 30. Journal of Food Science and Technology, 57(9); 3259–3266
European Medicines Agency (2003). ICH Topic Q1A (R2): Stability Testing of New Drug Substances and Products. Technical Report CPMP/ICH/2736/99, European Medicines Agency
Fitria, A., S. Hanifah, L. Chabib, A. M. Uno, H. Munawwarah, N. Atsil, and Y. Syukri (2021). Design and Characterization of Propolis Extract Loaded Self-Nano Emulsifying Drug Delivery System as Immunostimulant. Saudi Pharmaceutical Journal, 29(6); 625–634
Geng, Q., Y. Zhao, L. Wang, L. Xu, X. Chen, and J. Han (2020). Development and Evaluation of Astaxanthin as Nanostructure Lipid Carriers in Topical Delivery. AAPS PharmSciTech, 21(8); 318
Gloxhuber, C. (1974). Toxicological Properties of Surfactants. Archives of Toxicology, 32(4); 245–269
Gupta, T., J. Singh, S. Kaur, S. Sandhu, G. Singh, and I. P. Kaur (2020). Enhancing Bioavailability and Stability of Curcumin Using Solid LipidNanoparticles (CLEN): ACovenant for Its Effectiveness. Frontiers in Bioengineering and Biotechnology, 8; 879
Hariyadi, D. M., S. N. Sairiyah, F. W. Rahman, M. A. S. Rijal, N. Rosita, and M. Rahmadi (2024). Quercetin Solid Lipid Microparticle Stability and Deposition in Rat Lungs: A Study of Surfactant Effect. Science and Technology Indonesia, 9(3); 682–696
Kennedy, L. E., A. Abraham, G. Kulkarni, N. Shettigar, T. Dave, and M. Kulkarni (2021). Capsanthin, a Plant-Derived Xanthophyll: A Review of Pharmacology and Delivery Strategies. AAPS PharmSciTech, 22(5); 203
Khan, S., A. Sharma, and V. Jain (2023). An Overview of Nanostructured Lipid Carriers and Its Application in Drug Delivery Through Different Routes. Advanced Pharmaceutical Bulletin, 13(3); 446–460
Khan, S. A., S. B. Khan, L. U. Khan, A. Farooq, K. Akhtar, and A. M. Asiri (2018). Fourier Transform Infrared Spectroscopy: Fundamentals and Application in Functional Groups and Nanomaterials Characterization. In S. K. Sharma, editor, Handbook of Materials Characterization. Springer International Publishing, Cham, pages 317–344
Knoll, P., N. Hörmann, N.-M. Nguyen Le, R. Wibel, R. Gust, and A. Bernkop-Schnürch (2022). Charge Converting Nanostructured Lipid Carriers Containing a Cell-Penetrating Peptide for Enhanced Cellular Uptake. Journal of Colloid and Interface Science, 628; 463–475
Kulkarni, M., N. Goge, and A. A. Date (2020). Development of Nanoemulsion Preconcentrate of Capsanthin with Improved Chemical Stability. ASSAY and Drug Development Technologies, 18(1); 34–44
Lasoń, E., E. Sikora, and J. Ogonowski (2013). Influence of Process Parameters on Properties of Nanostructured Lipid Carriers (NLC) Formulation. Acta Biochimica Polonica, 60(4); 773–777
Liu,W.-Q., S.-Z. Yang, H.-Z. Gang, B.-Z. Mu, and J.-F. Liu (2020). Efficient Emulsifying Properties of Monoglycerides Synthesized via Simple and Green Route. Journal of Dispersion Science and Technology, 41(12); 1902–1910
Madaniyah, L., S. Fiddaroini, E. K. Hayati, M. F. Rahman, and A. Sabarudin (2025). Stability of Biologically Synthesized Silver Nanoparticles (AgNPs) Using Acalypha indica L. Plant Extract as Bioreductor and Their Potential as Anticancer Agents Against T47D Cells. Science and Technology Indonesia, 10(1); 101–110
Mahor, A. K., P. P. Singh, R. Gupta, P. Bhardwaj, P. Rathore, A. Kishore, and K. K. Bansal (2023). Nanostructured Lipid Carriers for Improved Delivery of Therapeutics via the Oral Route. Journal of Nanotechnology, 2023(1); 4687959
Nahrowi, R., S. Solehati,W.Widyastuti, N. L. G. R. Juliasih, K. D. Pandiangan, A. Setiawan, and J. Hendri (2024). New Encapsulation of Fucoxanthin Isolated from Cyclotella striata by Nano Chitosan–Pectin Using Ionic Gelation Method. Science and Technology Indonesia, 9(3); 517–528
Ocampo Osorio, F., E. N. Villanueva Badillo, D. G. Erazo Rondón, E. T. Muñoz Arango, A. A. Velásquez Salazar, A. A. Velasquez Torres, and C. L. Londoño Calderón (2023). Drug Loading Comparison of Commercial Ibuprofen on Magnetite Nanoparticles Surface by UV–Vis Spectrophotometry and Acid–Alkali Titration by a Factorial Design of Experiments. OpenNano, 14; 100193
Peczek, S. H., A. P. S. Tartari, I. C. Zittlau, C. Diedrich, C. S. Machado, and R. M. Mainardes (2023). Enhancing Oral Bioavailability and Brain Biodistribution of Perillyl Alcohol Using Nanostructured Lipid Carriers. Pharmaceuticals, 16(8); 1055
Pink, D. L., O. Loruthai, R. M. Ziolek, A. E. Terry, D. J. Barlow, M. J. Lawrence, and C. D. Lorenz (2021). Interplay of Lipid and Surfactant: Impact on Nanoparticle Structure. Journal of Colloid and Interface Science, 597; 278–288
Rodriguez-Ruiz, V., J. Á. Salatti-Dorado, A. Barzegari, A. Nicolas-Boluda, A. Houaoui, C. Caballo, and G. Pavon-Djavid (2018). Astaxanthin-Loaded Nanostructured Lipid Carriers for Preservation of Antioxidant Activity. Molecules, 23(10); 2601
Shah, R. M., S. R. Jadhav, G. Bryant, I. P. Kaur, and I. H. Harding (2025). On the Formation and Stability Mechanisms of Diverse Lipid-Based Nanostructures for Drug Delivery. Advances in Colloid and Interface Science, 338; 103402
Shevalkar, G. and P. Vavia (2019). Solidified Nanostructured Lipid Carrier (S-NLC) for Enhancing the Oral Bioavailability of Ezetimibe. Journal of Drug Delivery Science and Technology, 53; 101211
Smejkal, G., V. Gross, and A. Lazarev (2024). Theoretical and Experimental Determinations of theHydrophilic–Lipophilic Balance (HLB) of Representative Oils and Lecithins. Colloids and Interfaces, 8(2); 21
Subramaniam, B., Z. H. Siddik, and N. H. Nagoor (2020). Optimization of Nanostructured Lipid Carriers: Understanding the Types, Designs, and Parameters in the Process of Formulations. Journal of Nanoparticle Research, 22(6); 141
Varela-Fernández, R., X. García-Otero, V. Díaz-Tomé, U. Regueiro, M. López-López, M. González-Barcia, and F. J. Otero-Espinar (2022). Lactoferrin-Loaded Nanostructured Lipid Carriers (NLCs) as a New Formulation for Optimized Ocular Drug Delivery. European Journal of Pharmaceutics and Biopharmaceutics, 172; 144–156
Wang, Q., H. Zhang, Y. Han, Y. Cui, and X. Han (2023). Study on the Relationships Between the Oil HLB Value and Emulsion Stabilization. RSC Advances, 13(35); 24692–24698
Witayaudom, P. and U. Klinkesorn (2017). Effect of Surfactant Concentration and Solidification Temperature on the Characteristics and Stability of Nanostructured Lipid Carrier (NLC) Prepared from Rambutan (Nephelium lappaceum L.) Kernel Fat. Journal of Colloid and Interface Science, 505; 1082–1092
Yeo, S., M. J. Kim, Y. K. Shim, I. Yoon, and W. K. Lee (2022). Solid Lipid Nanoparticles of Curcumin Designed for Enhanced Bioavailability and Anticancer Efficiency. ACS Omega, 7(40); 35875–35884
Yousaf, R., M. I. Khan, M. F. Akhtar, A. Madni, M. F. Sohail, A. Saleem, and M. Rana (2023). Development and In-Vitro Evaluation of Chitosan and Glyceryl Monostearate Based Matrix Lipid Polymer Hybrid Nanoparticles (LPHNPs) for Oral Delivery of Itraconazole. Heliyon, 9(3); e14281
Yu, Y.-Q., X. Yang, X.-F. Wu, and Y.-B. Fan (2021). Enhancing Permeation of Drug Molecules Across the Skin via Delivery in Nanocarriers: Novel Strategies for Effective Transdermal Applications. Frontiers in Bioengineering and Biotechnology, 9; 646554
Zhang, T., Q. Peng, Y. Xia, Y. Zhang, K. Z. Myint, and J.Wu (2021). Steviol Glycosides, an Edible Sweet Surfactant That Can Modulate the Interfacial and Emulsifying Properties of Soy Protein Isolate Solution. Journal of Food Engineering, 289; 110264
Zhu, Y., X. Liang, C. Lu, Y. Kong, X. Tang, Y. Zhang, and H. He (2020). Nanostructured Lipid Carriers as Oral Delivery Systems for Improving Oral Bioavailability of Nintedanib by Promoting Intestinal Absorption. International Journal of Pharmaceutics, 586; 119569
Authors
Efiana, N. A., Shofa-ulhusna, F. ., Paramita, L. A., Heavena, I. A., Masyfiyah, S. F. ., Muhamed, F. ., Permadi, A. ., & Wahyuningsih, I. . (2026). Surfactant Variations in Capsanthin-loaded Nanostructured Lipid Carrier: Formulation, Characterization, and Stability Study. Science and Technology Indonesia, 11(1), 335–344. https://doi.org/10.26554/sti.2026.11.1.335-344
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