3.8(Q2)
CiteScore
27
h-index

Green Chemistry-Driven Development of Topical Vitamin D3 Nanostructured Lipid Carriers: In Silico Lipid Selection and Anti-Inflammatory Evaluation

Document Type : Original Research Article

Authors

1 Doctoral Program of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia

2 Faculty of Pharmacy, Institut Ilmu Kesehatan Bhakti Wiyata, Kediri, Indonesia

3 Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia

4 Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Malaya, Kuala Lumpur, Malaysia

5 Pharmaceutics and Delivery Systems for Drugs, Cosmetics and Nanomedicine (Pharm-DCN) Research Group of Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia

10.48309/ajgc.2026.563373.1879
Abstract
Vitamin D3 exhibits promising anti-inflammatory activity; however, its topical application is limited by poor aqueous solubility and low dermal bioavailability. Nanostructured lipid carriers (NLCs) are biocompatible lipid-based systems that enhance cutaneous delivery. This study optimized the lipid composition of Vitamin D3-loaded NLCs using an integrated green chemistry approach that combined in silico screening and experimental validation. Molecular docking and physicochemical compatibility prediction identified monostearin and Miglyol 812 as optimal lipid candidates. NLCs were then prepared at different solid–liquid lipid ratios (F1: 7:3, F2: 8:2, F3: 9:1) using an environmentally benign, organic-solvent-free high-shear homogenization process and were stabilized with a low concentration (3%) of non-ionic, low-toxicity surfactants (Tween 60 and PEG 400). In vitro release was assessed using UV–Vis spectrophotometry, and anti-inflammatory activity was evaluated using a carrageenan-induced paw edema model in rats. In vivo evaluation confirmed that formulation F1 produced the greatest reduction in paw edema (3.94% at 6 h), approaching the activity of the positive control and markedly outperforming the negative control. Overall, the combined in silico–experimental strategy improved the performance of vitamin D3-loaded NLCs while reducing material use and supporting environmentally benign formulation development.

Graphical Abstract

Green Chemistry-Driven Development of Topical Vitamin D3 Nanostructured Lipid Carriers: In Silico Lipid Selection and Anti-Inflammatory Evaluation

Keywords

Subjects


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[1] Yoshida, T., Beck, L.A., De Benedetto, A. Skin barrier defects in atopic dermatitis: From old idea to new opportunity. Allergology International, 2022, 71(1), 3-13.
[3] Liu, T., Zhang, L., Joo, D., Sun, S.C. Nf-κb signaling in inflammation. Signal Transduction and Targeted Therapy, 2017, 2(1), 1-9.
[4] Lin, Z., Li, W. The roles of vitamin d and its analogs in inflammatory diseases. Current Topics in Medicinal Chemistry, 2016, 16(11), 1242-1261.
[5] Zia, R., Nazir, A., Khan, M.K.I., Maan, A.A., Rashid, A. Preparation of ascorbic acid and cholecalciferol microsponges for topical application. International Journal of Pharmacy and Pharmaceutical Sciences, 2017, 9, 280-287.
[6] Al-Smadi, K., Imran, M., Abdoh, A., Liu, D., Phan, K., Filho, N.A., Leite-Silva, V.R., Mohammed, Y. Vitamin d-loaded lipid nanoparticles: Antioxidant properties, preparation, optimization, and in vitro characterization. Drug Delivery and Translational Research, 2025, 1-29.
[7] Kristianingsih, I., Hendradi, E., Siswodihardjo, S., Yuwono, M. Development and physicochemical characterization of nanostructured lipid carriers for entrapment of vitamin d3 prepared at different lipid ratios. Pharmacy Education, 2024, 24(3), 204-210.
[8] Azevedo, M.A., Cerqueira, M.A., Gonçalves, C., Amado, I.R., Teixeira, J.A., Pastrana, L. Encapsulation of vitamin d3 using rhamnolipids-based nanostructured lipid carriers. Food chemistry, 2023, 427, 136654.
[9] Mall, J., Naseem, N., Haider, M.F., Rahman, M.A., Khan, S., Siddiqui, S.N. Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications. Intelligent Pharmacy, 2024.
[10] Teeranachaideekul, V., Morakul, B., Boonme, P., Pornputtapitak, W., Junyaprasert, V. Effect of lipid and oil compositions on physicochemical properties and photoprotection of octyl methoxycinnamate-loaded nanostructured lipid carriers (nlc). Journal of Oleo Science, 2020, 69(12), 1627-1639.
[11] Haider, M., Abdin, S.M., Kamal, L., Orive, G. Nanostructured lipid carriers for delivery of chemotherapeutics: A review. Pharmaceutics, 2020, 12(3), 288.
[12] Aryani, N.L.D., Siswandono, S., Soeratri, W., Sari, D.R.K. Experimental development and molecular docking: Nanostructured lipid carriers (nlcs) of coenzyme q10 using stearic acid and different liquid lipids as lipid matrix. International Journal of Applied Pharmaceutics, 2021, 13(1), 108-116.
[13] Albasri, O.W.A., Kumar, P.V., Rajagopal, M.S. Development of computational in silico model for nano lipid carrier formulation of curcumin. Molecules, 2023, 28(4), 1833.
[14] Aryani, N.L.D., Siswodihardjo, S., Soeratri, W., Sari, N.F.I. Development, characterization, molecular docking, and in vivo skin penetration of coenzyme q10 nanostructured lipid carriers using tristearin and stearyl alcohol for dermal delivery. Journal of Basic and Clinical Physiology and Pharmacology, 2021, 32(4), 517-525.
[15] Leal, L.K.A.M., Lima, L.A., de Aquino, P.E.A., de Sousa, J.A.C., Gadelha, C.V.J., Calou, I.B.F., Lopes, M.J.P., Lima, F.A.V., Neves, K.R.T., de Andrade, G.M. Vitamin d (vd3) antioxidative and anti-inflammatory activities: Peripheral and central effects. European Journal of Pharmacology, 2020, 879, 173099.
[16] Çaykara, B., Öztürk, G., Mutlu, H.H., Arslan, E. Vitamin d, kalsiyum ve fosfor düzeyleri arasındaki İlişki. Journal of Academic Research in Medicine, 2020.
[17] Danimayostu, A.A., Lukitaningsih, E., Martien, R., Danarti, R. Determination of vitamin d3 loaded self-nanoemulsifying drug delivery systems (snedds) based hydrogel. Journal of Research in Pharmacy, 2023, 27(3), 1213-1219.
[18] Allegra, S., Chiara, F., Di Grazia, D., Gaspari, M., De Francia, S. Evaluation of sex differences in preclinical pharmacology research: How far is left to go? Pharmaceuticals, 2023, 16(6), 786.
[19] Tsao, C.H., Wu, K.Y., Su, N.C., Edwards, A., Huang, G.J. The influence of sex difference on behavior and adult hippocampal neurogenesis in c57bl/6 mice. Scientific reports, 2023, 13(1), 17297.
[20] Elmowafy, M., Al-Sanea, M.M. Nanostructured lipid carriers (nlcs) as drug delivery platform: Advances in formulation and delivery strategies. Saudi Pharmaceutical Journal, 2021, 29(9), 999-1012.
[21] Suyuti, A., Hendradi, E., Purwanti, T., Effect of different lipid ratios on physicochemical stability and drug release of nanostructured lipid carriers loaded coenzyme q10. J. Farm. Dan Ilmu Kefarmasian Indones, 2023, 10(1), 44-53.
[22] Chauhan, I., Yasir, M., Verma, M., Singh, A.P. Nanostructured lipid carriers: A groundbreaking approach for transdermal drug delivery. Advanced Pharmaceutical Bulletin, 2020, 10(2), 150.
[23] Seo, T.R., Lee, I., Chun, Y.G., Park, D.J., Lee, S.H., Kim, B.K. Improved stability of polyglycerol polyricinoleate‐substituted nanostructured lipid carrier cholecalciferol emulsions with different carrier oils. Journal of Food Science, 2019, 84(4), 782-791.
[24] Tamjidi, F., Shahedi, M., Varshosaz, J., Nasirpour, A. Nanostructured lipid carriers (nlc): A potential delivery system for bioactive food molecules. Innovative Food Science & Emerging Technologies, 2013, 19, 29-43.
[25] Jafarifar, Z., Rezaie, M., Sharifan, P., Jahani, V., Daneshmand, S., Ghazizadeh, H., Ferns, G.A., Golmohammadzadeh, S., Ghayour-Mobarhan, M. Preparation and characterization of nanostructured lipid carrier (nlc) and nanoemulsion containing vitamin d3. Applied Biochemistry and Biotechnology, 2022, 194(2), 914-929.

Articles in Press, Accepted Manuscript
Available Online from 30 January 2026

  • Receive Date 12 November 2025
  • Revise Date 17 December 2025
  • Accept Date 26 January 2026