Ketorolac Tromethamine Loaded Nano-Spray Dried Nanoparticles: Prep-aration, Characterization, Cell Viability, COL1A1 Gene Simulation and Determination of Anti-inflammatory Activity by In vivo HET-CAM Assay

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Öztürk A. A., Çevikelli T., Kaya Tilki E., Güven U. M., Kıyan H. T.

Current Drug Delivery, vol.20, no.6, pp.830-840, 2023 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 20 Issue: 6
  • Publication Date: 2023
  • Doi Number: 10.2174/1567201820666230125144133
  • Journal Name: Current Drug Delivery
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, EMBASE, MEDLINE
  • Page Numbers: pp.830-840
  • Keywords: COL1A1, HET-CAM, Ketorolac tromethamine, KT-NP, nanoparticle, RT-PCR, wound
  • Anadolu University Affiliated: Yes


Background: Ketorolac tromethamine (KT) is a non-steroidal anti-inflammatory drug from the heteroaryl acetic acid derivatives family. The most widely used new nanotechnological approaches for topical drug delivery are polymeric nanoparticles (NPs). Objective: Successful results have been obtained with low doses in many treatments, such as cancer, antimicrobial, pain, made with nanoparticle formulations of drug active ingredients. Methods: NPs were prepared using Nano Spray-Dryer. The cytotoxicity of the optimum formulation in BJ (ATCC® CRL-2522™) human fibroblast cells was determined by the WST-1 method and the gene activity was elucidated by mRNA isolation and real-time polymerase chain reaction (RT-PCR). The in vivo HET-CAM assay was performed for anti-inflammatory activity. Results: NPs presented PDI values lower than 0.5, and therefore particle size distribution was decided to be monodisperse. Positive zeta potential values of NPs highlighted the presence of the cationic am-monium group of Eudragit® RS 100. The release rates observed from KT-NP coded formulations after 24 hours were 78.4% ± 2.9, demonstrating extended release from all formulations, relative to pure KT. The lowest concentration of KT-NP increased fibroblast cell proliferation higher than the highest concentration of KT. The 5-fold increased effect of KT-NP formulation on collagen gene expression com-pared to KT is also related to the enhanced anti-inflammatory effect in line with the in vivo HET-CAM assay results. Conclusion: With the obtained cell viability, gene expression, and HET-CAM results, it has the hope of a successful nano-topical formulation, especially in both wound healing and anti-inflammatory treat-ment.