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Enhancing collagen based nanoemulgel for effective topical delivery of Aceclofenac and Citronellol oil: Formulation, optimization, in-vitro evaluation, and in-vivo osteoarthritis study with a focus on HMGB-1/RAGE/NF-κB pathway, Klotho, and miR-499a.
Aldeeb, Reem Abd Elhameed; Ibrahim, Sherihan Salaheldin Abdelhamid; Khalil, Islam Ahmed; Ragab, Ghada Mohamed; El-Gazar, Amira Ahmed; Taha, Amal Anwar; Hassan, Doaa Hussien; Gomaa, Asmaa Ahmed; Younis, Mona Kamal.
Afiliación
  • Aldeeb RAE; Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt. reem.eldeeb@must.edu.eg.
  • Ibrahim SSA; Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University, Alexandria, Egypt.
  • Khalil IA; Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.
  • Ragab GM; Department of Pharmacology and Toxicology, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.
  • El-Gazar AA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, October 6 University, 12585, Egypt.
  • Taha AA; Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.
  • Hassan DH; Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.
  • Gomaa AA; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, 12585, Egypt.
  • Younis MK; Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, 12566, Egypt.
Article en En | MEDLINE | ID: mdl-38502267
ABSTRACT
The majority of conventional osteoarthritis (OA) treatments are based on molecular adjustment of certain signaling pathways associated with osteoarthritis (OA) pathogenesis, however there is a significant need to search for more effective and safe treatments. This study centers around formulating Aceclofenac (ACF) with high bioavailability in combination with Citronellol oil and collagen. The optimal concentrations of Citronellol oil/D-Limonene oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were studied for thermophysical stability. Thermodynamically stable formula were analyzed for droplet size, zeta potential, and in-vitro permeation. Then, collagen based nanoemulsion were prepared to capitalize on its efficacy in reducing osteoarthritis side effects and characterized for nano size properties. Formulae F10 and F10C were chosen as optimum nanosize formula. Hense, they were prepared and characterized as nanoemulgel dosage form. The nanoemulgel formulae F10NEG1 and F10CNEG1 showed reasonable viscosity and spreadability, with complete drug release after 4 h. These formulae were chosen for further In vivo anti-OA study. Collagen based ACF/citronellol emugel were able to modulate HMGB-1/RAGE/NF-κB pathway, mitigating the production of inflammatory cytokine TNF-α. They were also able to modulate Klotho and miR-499, reducing serum CTXII and COMP, by reducing the cartilage destruction. Histological investigations validated the efficacy, safety, and superiority of Aceclofenac in combination with Citronellol oil and collagen (F10CNEG1) over solo the treated group (F10NEG1 and blank). Hence, the findings of the current work encourage the use of this promising combined formula in treatment of OA patients.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Drug Deliv Transl Res Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Drug Deliv Transl Res Año: 2024 Tipo del documento: Article País de afiliación: Egipto Pais de publicación: Estados Unidos