International Journal of Drug Delivery Technology
Volume 15, Issue 3

Formulation and Evaluation of Nanoemulsion-Based Gels Containing Chrysophanol for Topical Fungal Treatment: A Quality by Design Approach

Kanchan Sanjivan Kakade*, Kiran Sanjay Bhise

MCES's Allana College of Pharmacy Pune, Maharashtra, India

Received: 5th Jun, 2025; Revised: 17th Jul, 2025; Accepted: 29th Jul, 2025; Available Online: 25th Sep, 2025 

ABSTRACT

Fungal skin infections remain a clinical challenge and motivate development of alternative topical therapeutics. Chrysophanol, a natural anthraquinone, has limited cutaneous bioavailability, prompting formulation into nanocarriers to enhance delivery. In this study, Chrysophanol-loaded nanoemulsion (NE) and a corresponding nanogel were developed and optimized for dermal application. The optimized NE (F13) exhibited a mean droplet size of 231 nm, zeta potential −23 mV, and high entrapment efficiency (97.65 ± 0.35%). The nanogel displayed dermally acceptable pH (6.25 ± 0.11) and suitable rheology/spreadability. In vitro release studies confirmed sustained release (98.84 ± 2.59% from NE; 96.47 ± 2.96% from the nanogel). Functional evaluation was performed using in vitro antifungal enzyme inhibition assays targeting phospholipases and proteases. Relative to the pure extract, the NE increased inhibition to 61.37 ± 1.45% (phospholipase) and 55.29 ± 1.28% (protease), while the nanogel achieved 73.25 ± 1.62% and 69.84 ± 1.37%, respectively, approaching the standard ketoconazole (79.41 ± 1.18% and 74.92 ± 1.04%). These findings indicate that Chrysophanol nanocarriers improved enzyme-level antifungal activity while providing favorable physicochemical attributes for topical use, supporting their further development as promising natural antifungal formulations.

Keywords: Chrysophanol, NE, Nanogel, Antifungal therapy, Topical drug delivery, Quality by Design

How to cite this article: Kanchan Sanjivan Kakade, Kiran Sanjay Bhise. Formulation and Evaluation of Nanoemulsion-Based Gels Containing Chrysophanol for Topical Fungal Treatment: A Quality by Design Approach. International Journal of Drug Delivery Technology. 2025;15(3):1177-86. doi: 10.25258/ijddt.15.3.37

REFERENCES

  1. Corzo-León DE, Munro CA, MacCallum DM. An ex vivo human skin model to study superficial fungal infections. Front Microbiol. 2019;10(JUN).
  2. Hay R. Therapy of skin, hair and nail fungal infections. J Fungi. 2018;4(3).
  3. Verma S, Utreja P. Vesicular nanocarrier based treatment of skin fungal infections: Potential and emerging trends in nanoscale pharmacotherapy. Asian J Pharm Sci. 2019;14(2):117–29.
  4. Garg A, Sharma GS, Goyal AK, Ghosh G, Si SC, Rath G. Recent advances in topical carriers of anti-fungal agents. Heliyon. 2020;6(8).
  5. Hur MS, Park M, Jung WH, Lee YW. Evaluation of drug susceptibility test for Efinaconazole compared with conventional antifungal agents. Mycoses. 2019;62(3):291–7.
  6. Yassin MT, Elgorban AM, Al-Askar AA, Sholkamy EN, Ameen F, Maniah K. Synergistic Anticandidal Activities of Greenly Synthesized ZnO Nanomaterials with Commercial Antifungal Agents against Candidal Infections. Micromachines. 2023;14(1).
  7. Seo EJ, Ngoc TM, Lee SM, Kim YS, Jung YS. Chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant activities. J Pharmacol Sci. 2012;118(2):245–54.
  8. Deitersen J, El-Kashef DH, Proksch P, Stork B. Anthraquinones and autophagy – Three rings to rule them all? Bioorganic Med Chem. 2019;27(20).
  9. Park DB, Park BS, Kang HM, Kim JH, Kim IR. Chrysophanol-Induced Autophagy Disrupts Apoptosis via the PI3K/Akt/mTOR Pathway in Oral Squamous Cell Carcinoma Cells. Med. 2023;59(1).
  10. Prateeksha, Yusuf MA, Singh BN, Sudheer S, Kharwar RN, Siddiqui S, et al. Chrysophanol: A natural anthraquinone with multifaceted biotherapeutic potential. Biomolecules. 2019;9(2).
  11. Zhang G, Li J, Lv H, Qian C, Li X, Yang Z, et al. Comparative pharmacokinetics of rhubarb anthraquinones loaded nanoemulsion by different plasma drug concentration calculation methods. Acta Pol Pharm - Drug Res. 2021;78(4):475–83.
  12. Nasiri MI, Vora LK, Ershaid JA, Peng K, Tekko IA, Donnelly RF. Nanoemulsion-based dissolving microneedle arrays for enhanced intradermal and transdermal delivery. Drug Deliv Transl Res. 2022;12(4):881–96.
  13. Latif MS, Nawaz A, Asmari M, Uddin J, Ullah H, Ahmad S. Formulation Development and In Vitro/In Vivo Characterization of Methotrexate-Loaded Nanoemulsion Gel Formulations for Enhanced Topical Delivery. Gels. 2023;9(1).
  14. Alqarni MH, Foudah AI, Aodah AH, Alkholifi FK, Salkini MA, Alam A. Caraway Nanoemulsion Gel: A Potential Antibacterial Treatment against Escherichia coli and Staphylococcus aureus. Gels. 2023;9(3).
  15. Prohit PV, Pakhare PS, Pawar VB, Dandade SS, Waghmare MS, Shaikh FA, et al. Formulation and Comparative Evaluation of Naproxen-Based Transdermal Gels. J Pharm Sci Comput Chem. 2025;1(2):83–105.
  16. Özcan S, Levent S, Can NÖ. Quality by design approach with design of experiment for sample preparation techniques. Adv Sample Prep. 2023;7.
  17. Sangshetti JN, Deshpande M, Zaheer Z, Shinde DB, Arote R. Quality by design approach: Regulatory need. Arab J Chem. 2017;10:S3412–25.
  18. Khanahmadi M, Shahrezaei F, Sharifi M, Rezanejade Bardajee G. Ultrasound-Assisted Preparation and Optimization of Natural Flavoring Nanoemulsion for Dairy Products Based on Pistacia Khinjuk in Lab Scale. Chem Methodol. 2023;7(7):524–39.
  19. Kumar RR, Krishnan K, Sankararao G, Samathoti P, Kumar JP, Bagade OM, et al. Biochemical Engineering of Green Nanomaterials for Targeted Drug Delivery and Therapeutic Applications. J Chem Rev. 2025;6(3):191–215.
  20. Reddy KTK, Dharmamoorthy G, Devi DV, Vidiyala N, Bagade OM, Elumalai S, et al. Phytoconstituent-Based Green Synthesis of Nanoparticles: Sources and Biomedical Applications in Cancer Therapy. Asian J Green Chem. 2025;9(3):329–54.
  21. Dayyih WA, Awad R. Revolutionizing drug development: The role of AI in modern pharmaceutical research. J Pharm Sci Comput Chem. 2025;1(1):206–27.
  22. Nagda D, Captain A. Validated Green Densitometric Method for Estimation of Naringin Biomarker in Hydroalcoholic Extract of Leaves of Ceiba Pentandra ( L .) Gaertn. Asian J Green Chem. 2025;9:427–42.
  23. Abdullah MN, El Arbi M. Silver Nano Loaded Solanum Nigrum with Potential Biological Activities. Chem Methodol. 2024;8(8):585–602.
  24. Chandramore KR, Sonawane SS, Ahire RS, Reddy H, Ahire SB, Jadhav PB, et al. Development and Validation of Stability Indicating LC Method for Selexipag : In-Silico Toxicity Study and Characterization of its Degradation Products. Chem Methodol. 2025;9:427–47.
  25. Ajeed A, Billah M, Babu RH, D KK, Bubalan K, Bhuvaneshwari G, et al. Phyto-Nanotechnology for Cancer Therapy : A Review of Plant-Mediated Organic Nanoparticles for Targeted Drug Delivery. J Chem Rev. 2025;7(2):131–65.
  26. Prinsa, Rana AJ, Saha S, Chaudhary M, Kumar K, Kausar M, et al. Molecular Docking, MD Simulation, Synthesis, DFT, and Biological Evaluations of Newer Generation Imidazolo-Triazole Hydroxamic Acid Linked with Para Nitro Phenyl Group. Adv J Chem Sect A. 2025;8(7):1171–87.
  27. Trabelsi R, Yengui M. Green Synthesis of MgZnFe₂O₄ Nanoparticles : A Sustainable Approach to Combat β -Lactam-Resistant Uropathogenic Strains. Chem Methodol. 2025;9:489–507.
  28. Alabady AA, Al-Majidi SMH. Synthesis, characterization, and evaluation of molecular docking and experimented antioxidant activity of some new chloro azetidine-2-one and diazetine-2-one derivatives from 2-phenyl-3-amino-quinazoline-4(3H)-one. J Med Pharm Chem Res. 2023;5(1):1–18.
  29. Ali DN, Ahmed A, Al-Qaisi AHJ. Inhibitory Effect of Newly Prepared Pyrazole Derivatives against Alpha-Amylase in Pancreatic Cancer Cell. Adv J Chem Sect A. 2024;7(3):248–59.
  30. Vattikundala P, Chaudhary S, Sumithra M. Design, preparation, characterization, and evaluation of NR4A1 agonist novel 6-mercaptopurine monohydrate loaded nanostructured lipid carriers suspension for enhanced solubility and in vivo J Med Pharm Chem Res. 2025;7(6):1059–78.
  31. Dolatyari A, Nilchi A, Janitabardarzi S, Alipour A, Hashemi M. Evaluation of Ze/PAN Nanocomposites for Adsorption of Cs (Ι) from Aaqueous Environments. Chem Methodol. 2025;9(2):103–24.
  32. Díaz de los Ríos M, Hernández Ramos E. Determination of the Hansen solubility parameters and the Hansen sphere radius with the aid of the solver add-in of Microsoft Excel. SN Appl Sci. 2020;2(4).
  33. Veseli A, Žakelj S, Kristl A. A review of methods for solubility determination in biopharmaceutical drug characterization. Vol. 45, Drug Development and Industrial Pharmacy. 2019. p. 1717–24.
  34. Kitak T, Dumičič A, Planinšek O, Šibanc R, Srčič S. Determination of solubility parameters of ibuprofen and ibuprofen lysinate. Molecules. 2015;20(12):21549–68.
  35. Abass AM, Abdoon FM. Synthesis, Characterization, and Applications of Metal Oxides of ZnO, CuO, and CeO2 Nanoparticles: A Review. J Appl Organomet Chem. 2024;4(4):349–66.
  36. Prasath H, Azhakesan A, Manikandan G. Analytical Methods for Quantification of Gemcitabine in Pharmaceutical and Biological Samples : An Overview of Developments in the Last Decade. Asian J Green Chem. 2025;9:457–75.