Kojic Monooleate Loaded Nanostructured Lipid Carriers (NLCs) for Enhanced Sunscreen Formulation: Optimisation via Response Surface Methodology

Authors

  • Nur Farah Syazwahazwani Sufatan Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor, Malaysia.
  • Siti Efliza Ashari Bioprocessing & Biomanufacturing Research Group, University Driven Research Group, Universiti Putra Malaysia, 43400 UPM, Serdang, Selangor Malaysia.

DOI:

https://doi.org/10.54987/jobimb.v14i1.822

Keywords:

Nanostructured lipid carriers, Kojic monooleate, Sunscreen formulation, Tyrosinase inhibition, Response Surface Methodology

Abstract

Nanostructured lipid carriers (NLCs) are promising topical delivery systems for improving the dispersion and formulation performance of lipophilic cosmeceutical actives. Chronic ultraviolet (UV) exposure contributes to photoageing and hyperpigmentation, creating a demand for multifunctional sunscreen formulations that provide photoprotection together with tyrosinase inhibition. This study aimed to formulate and optimise a kojic monooleate (KMO)-containing NLC sunscreen using sun protection factor (SPF) as the primary optimisation response. KMO was incorporated as a tyrosinase-inhibitory active together with titanium dioxide, zinc oxide and avobenzone as UV filters. NLCs were prepared by bath ultrasonication followed by high-shear homogenisation, and a D-optimal response surface methodology was applied to optimise the formulation. Analysis of variance demonstrated that the quadratic model was significant (F = 196.33, p < 0.05) with a non-significant lack of fit, indicating good model predictability. The optimised formulation achieved an in vitro SPF of 38.88, a mean particle size of 170.10 nm, a polydispersity index of 0.326 and a pH of 4.88. No visible phase separation was observed after centrifugation, whereas freeze–thaw cycling increased particle size and polydispersity index, indicating reduced colloidal stability under thermal stress. The optimised formulation also exhibited acceptable spreadability and 78.08% mushroom tyrosinase inhibition at 250 µg/mL. These findings provide preliminary evidence supporting the potential of KMO-containing NLCs as SPF-oriented multifunctional sunscreen formulations. However, further evaluation of UVA protection, critical wavelength, photostability, comprehensive nanoparticle characterisation and cell-based melanogenesis is required before broad-spectrum photoprotection and biological depigmenting efficacy can be established.

References

1 Gaikwad S, Kasture A. Nanostructured lipid carriers in cosmeceuticals. Int J Creat Res Thoughts. 2024;12(5):317–322.

2 Javed S, Mangla B, Almoshari Y, Sultan MH, Ahsan W. Nanostructured lipid carrier system: a compendium of their formulation development approaches, optimization strategies by quality by design, and recent applications in drug delivery. Nanotechnol Rev. 2022;11(1):1744–1777. https://doi.org/10.1515/ntrev-2022-0109

3 Meticulous Research. Sunscreen market by product type, SPF range, form, distribution channel, end user and geography global forecast to 2035. 2025 (cited 2026 Jul 23). Available from: https://www.meticulousresearch.com/product/sunscreen-market-6173

4 Salvi VR, Pawar P. Nanostructured lipid carriers (NLC) system: a novel drug targeting carrier. J Drug Deliv Sci Technol. 2019;51:255–267. https://doi.org/10.1016/j.jddst.2019.02.017

5 Ghasemiyeh P, Mohammadi-Samani S. Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages. Res Pharm Sci. 2018;13(4):288–303. https://doi.org/10.4103/1735-5362.235156

6 Chu CC, Hasan ZAA, Tan CP, Nyam KL. In vitro safety evaluation of sunscreen formulation from nanostructured lipid carriers using human cells and skin model. Toxicol In Vitro. 2022;84:105431. https://doi.org/10.1016/j.tiv.2022.105431

7 Therapeutic Goods Administration. Literature review on the safety of titanium dioxide and zinc oxide nanoparticles in sunscreens (Internet). Canberra: Australian Government Department of Health; 2017 Available from: https://www.tga.gov.au/resources/publication/corporate-reports/literature-review-safety-titanium-dioxide-and-zinc-oxide-nanoparticles-sunscreens

8 Syed Azhar SNF, Ashari SE, Salim N. Development of a kojic monooleate-enriched oil-in-water nanoemulsion as a potential carrier for hyperpigmentation treatment. Int J Nanomedicine. 2018;13:6465–6479. https://doi.org/10.2147/IJN.S171532

9 Lajis AFB, Hamid M, Ariff AB. Depigmenting effect of kojic acid esters in hyperpigmented B16F1 melanoma cells. J Biomed Biotechnol. 2012;2012:952452. https://doi.org/10.1155/2012/952452

10 Subramaniam B, Siddik ZH, Nagoor NH. Optimisation of nanostructured lipid carriers: understanding the types, designs, and parameters in the process of formulations. J Nanopart Res. 2020;22(6):141. https://doi.org/10.1007/s11051-020-04848-0

11 International Organization for Standardization. ISO 24443:2021 Cosmetics—Determination of sunscreen UVA photoprotection in vitro (Internet). 2nd ed. Geneva: International Organization for Standardization; 2021 (cited 2026 Jul 23). Available from: https://www.iso.org/standard/75059.html

12 U.S. Food and Drug Administration. Labeling and effectiveness testing: sunscreen drug products for over-the-counter human use—small entity compliance guide (Internet). Silver Spring (MD): U.S. Food and Drug Administration; 2012 (cited 2026 Jul 23). Available from: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/labeling-and-effectiveness-testing-sunscreen-drug-products-over-counter-human-use-small-entity

13 Jumbri K, Rozy MFA, Ashari SE, Mohamad R, Basri M, Masoumi HRF. Optimisation and characterisation of lipase-catalysed synthesis of a kojic monooleate ester in a solvent-free system by response surface methodology. PLoS One. 2015;10(12):e0144664. https://doi.org/10.1371/journal.pone.0144664

14 International Organization for Standardization. ISO 22412:2025 Particle size analysis—Dynamic light scattering (DLS). 3rd ed. Geneva: International Organization for Standardization; 2025. https://www.iso.org/standard/85505.html

15 Stetefeld J, McKenna SA, Patel TR. Dynamic light scattering: a practical guide and applications in biomedical sciences. Biophys Rev. 2016;8(4):409–427. https://doi.org/10.1007/s12551-016-0218-6

16 Hou P, Pu F, Zou H, Diao M, Zhao C, Xi C, et al. Whey protein-stabilized nanoemulsion: a potential delivery system for ginsenoside Rg3. Food Biosci. 2019;31:100427. https://doi.org/10.1016/j.fbio.2019.100427

17 Garg A, Aggarwal D, Garg S, Singla AK. Spreading of semisolid formulations: an update. Pharm Technol. 2002;26(9):84–105.

18 Varma VNSK, Maheshwari PV, Navya M, Reddy SC, Shivakumar HG, Gowda DV. Calcipotriol delivery into the skin as emulgel for effective permeation. Saudi Pharm J. 2014;22(6):591–599. https://doi.org/10.1016/j.jsps.2014.02.007

19 Qian Y, Qiu X, Zhu S. Sunscreen performance of lignin from different technical resources and their general synergistic effect with synthetic sunscreens. ACS Sustain Chem Eng. 2016;4(7):4029–4035. https://doi.org/10.1021/acssuschemeng.6b00934

20 Roselan MA, Zakaria N, Faujan NH, Mohammad Latif MA, Mohd Faudzi SM, Ab Hadi H, et al. In vitro cytotoxicity assay, mushroom tyrosinase inhibitory activity and release analysis of kojic monooleate nanodelivery system and in silico molecular docking study against 2Y9X target enzyme. J Drug Deliv Sci Technol. 2021;66:102764. https://doi.org/10.1016/j.jddst.2021.102764

21 Ghamarpoor R, Fallah A, Jamshidi M. Investigating the use of titanium dioxide (TiO₂) nanoparticles on the amount of protection against UV irradiation. Sci Rep. 2023;13(1):9793. https://doi.org/10.1038/s41598-023-37057-5

22 Abdel-Salam FS, Ammar HO, Elkheshen SA, Mahmoud AA. Anti-inflammatory sunscreen nanostructured lipid carrier formulations. J Drug Deliv Sci Technol. 2017;37:13–19. https://doi.org/10.1016/j.jddst.2016.10.014

23 Date PV, Samad A, Devarajan PV. Freeze thaw: a simple approach for prediction of optimal cryoprotectant for freeze drying. AAPS PharmSciTech. 2010;11(1):304–313. https://doi.org/10.1208/s12249-010-9382-3

24 Lin CC, Lin WJ. Sun protection factor analysis of sunscreens containing titanium dioxide nanoparticles. J Food Drug Anal. 2011;19(1):1–8. https://doi.org/10.38212/2224-6614.2181

25 Beasley DG, Meyer TA. Characterization of the UVA protection provided by avobenzone, zinc oxide, and titanium dioxide in broad-spectrum sunscreen products. Am J Clin Dermatol. 2010;11(6):413–421. https://doi.org/10.2165/11537050-000000000-00000

26 Puglia C, Damiani E, Offerta A, Rizza L, Tirendi GG, Tarico MS, et al. Evaluation of nanostructured lipid carriers and nanoemulsions as carriers for UV filters: characterization, in vitro penetration and photostability studies. Eur J Pharm Sci. 2014;51:211–217. https://doi.org/10.1016/j.ejps.2013.09.023

27 de Araújo MM, Schneid AC, Oliveira MS, Mussi SV, de Freitas MN, Carvalho FC, et al. NLC-based sunscreen formulations with optimized proportion of encapsulated and free filters exhibit enhanced UVA and UVB photoprotection. Pharmaceutics. 2024;16(3):427. https://doi.org/10.3390/pharmaceutics16030427

28 Nash JF, Tanner PR. Relevance of UV filter/sunscreen product photostability to human safety. Photodermatol Photoimmunol Photomed. 2014;30(2–3):88–95. https://doi.org/10.1111/phpp.12113

29 Bonda CA. The photostability of organic sunscreen actives: a review. In: Shaath NA, editor. Sunscreens: regulations and commercial development. 3rd ed. Boca Raton (FL): CRC Press; 2005. p. 321–349. https://doi.org/10.1201/b14170-25

30 Kaur CD, Saraf S. In vitro sun protection factor determination of herbal oils used in cosmetics. Pharmacogn Res. 2010;2(1):22–25. https://doi.org/10.4103/0974-8490.60586

31 Rahmasari D, Putri NS, Pranita EN, Nadifa N, Anggraeni AD. Development of emulsion gel sunscreen containing olive oil and clove oil. KnE Med. 2022;2(3):141–148. https://doi.org/10.18502/kme.v2i3.11862

32 Sabzevari N, Qiblawi SH, Norton SA, Fivenson DP. Sunscreens: UV filters to protect us. Part 1: changing regulations and choices for optimal sun protection. Int J Womens Dermatol. 2021;7(1):28–44. https://doi.org/10.1016/j.ijwd.2020.05.017

33 Sahraee S, Ghanbarzadeh B, Mohammadi M, Pezeshki A, Hoseini M. Development of heat-stable gelatin-coated nanostructured lipid carriers: colloidal and stability properties. LWT. 2022;160:113265. https://doi.org/10.1016/j.lwt.2022.113265

34 Khosa A, Reddi S, Saha RN. Nanostructured lipid carriers for site-specific drug delivery. Biomed Pharmacother. 2018;103:598–613. https://doi.org/10.1016/j.biopha.2018.04.055

35 Lukić M, Pantelić I, Savić SD. Towards optimal pH of the skin and topical formulations: from the current state of the art to tailored products. Cosmetics. 2021;8(3):69. https://doi.org/10.3390/cosmetics8030069

36 Smaoui S, Ben Hlima H, Jarraya R, Kamoun NG, Ellouze R, Damak M. Cosmetic emulsion from virgin olive oil: formulation and bio-physical evaluation. Afr J Biotechnol. 2012;11(40):9664–9671. https://doi.org/10.5897/AJB12.163

37 Al-Sarraf MA, Hussein AA, Al-Sarraf ZA. Comparison between conventional gel and nanostructured lipid carrier gel of zaltoprofen: preparation and in vitro/ex vivo evaluation. Int J Drug Deliv Technol. 2021;11(3):988–995. https://doi.org/10.25258/ijddt.11.3.57

38 Chatatikun M, Tedasen A, Pattaranggoon NC, Palachum W, Chuaijit S, Mudpan A, et al. Antioxidant activity, anti-tyrosinase activity, molecular docking studies, and molecular dynamic simulation of active compounds found in nipa palm vinegar. PeerJ. 2023;11:e16494. https://doi.org/10.7717/peerj.16494

39 Jaslina NF, Ashari SE, Mohamad R, Faujan NH. In vitro and antioxidant evaluation of a nanoemulsion formulation containing kojic monooleate for hyperpigmentation treatment. Malays J Chem. 2021;23(4):37–48. https://doi.org/10.55373/mjchem.v23i4.1185

40 Organisation for Economic Co-operation and Development. Test No. 439: In vitro skin irritation: reconstructed human epidermis test method. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2025. https://doi.org/10.1787/9789264242845-en

41 Organisation for Economic Co-operation and Development. Test No. 432: In vitro 3T3 NRU phototoxicity test. OECD Guidelines for the Testing of Chemicals, Section 4. Paris: OECD Publishing; 2019. https://doi.org/10.1787/9789264071162-en

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31.07.2026

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How to Cite

Kojic Monooleate Loaded Nanostructured Lipid Carriers (NLCs) for Enhanced Sunscreen Formulation: Optimisation via Response Surface Methodology. (2026). Journal of Biochemistry, Microbiology and Biotechnology, 14(1), 28-36. https://doi.org/10.54987/jobimb.v14i1.822