Optimization of Semi-Solid Lipid Nanoparticle Dispersions by Quality by Design Approach for Dermal Delivery of Curcumin


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BADILLI F. U., Sen A., Yegen G., GÜVEN ÇİLOĞLU B., Aksu B., Onay Besikci A.

Journal of Cluster Science, cilt.36, sa.5, 2025 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 36 Sayı: 5
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s10876-025-02915-x
  • Dergi Adı: Journal of Cluster Science
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Chemical Abstracts Core, Communication Abstracts, Metadex, DIALNET, Civil Engineering Abstracts
  • Anahtar Kelimeler: Artificial neural network, Carrageenan, Curcumin, Optimization, Quality by design, Semi-solid NLC, Semi-solid SLN, Texture profile analysis
  • Ankara Üniversitesi Adresli: Evet

Özet

Curcumin is an important anti-inflammatory agent for the treatment of skin disorders. However, its low water solubility, poor bioavailability, and instability limit the utilization of curcumin. Semi-solid lipid nanoparticle (SLN and NLC) dispersions, which maintain their colloidal particle size despite their high viscosity, offer a novel promising approach with high potential for dermal curcumin delivery. In this study, novel semi-solid SLN-NLC formulations of curcumin were manufactured using a one-step method, without the need to disperse the nanoparticles in an additional vehicle. Modde Pro 12 was used to examine the relationship between variables and quality attributes. QbD-based formulation optimization was successfully performed using artificial neural network program (ANN), and optimum semi-solid SLN-NLC formulations were prepared. The particle size of the optimum formulations was found to be 204.7 ± 1.5 nm for SS-SLN-Opt and 198.5 ± 0.81 nm for SS-NLC-Opt, indicating that the particle sizes were within the targeted range. The amount of curcumin released from the SS-NLC-Opt formulation was 33.72 ± 4.99% at 24th Hour, which was higher than the release obtained from the eight SS-NLC formulations entered as input into the ANN program. On the other hand, while the curcumin release percentage at the 24th Hour from the SS-SLN formulations entered into the program ranged between 11.13% and 44.31%, the release amount for the SS-SLN-Opt formulation was found to be 38.34 ± 3.48%, which was within this range and close to the maximum value. Rheological characterization results indicated that the optimum semi-solid SLN and NLC formulations were more elastic than viscous. The stability of the optimum semi-solid SLN formulation at 4 °C was higher than that of the optimum semi-solid NLC after one month. In vivo studies in rats revealed that the optimum semi-solid SLN formulation exhibited higher anti-inflammatory activity than both the optimum semi-solid NLC and the conventional gel. The SS-SLN-Opt formulation effectively reduced the inflammation in rats starting from the first hour. In conclusion, the optimum semi-solid SLN formulation, which is more stable and has higher anti-inflammatory activity, is a promising alternative for the dermal delivery of curcumin.