Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study.

The article presents an experimental study on the possible repurposed use of valsartan (Val), in the local treatment of uncontrolled diabetic foot ulcer. Solid lipid nanoparticles (SLN), loaded with Val were prepared by applying 32 full factorial design using modified high shear homogenization method. The lipid phase composed of Precirol® ATO 5 (P ATO 5) and/or Gelucire 50/13 (G 50/13) in different ratios and a nonionic emulsifier, Pluronic 188 (P188), was used in different percentages. Optimized formulation was further integrated in hydroxyl propyl methyl cellulose (HPMC) gel for the ease of administration. In-vitro and in-vivo characterizations were investigated. The prepared nanoparticles showed small particle size, high entrapment efficiency and sustained drug release. Microbiologically, Val-SLN showed a prominent decrease in the biofilm mass formation for both gram-positive and gram-negative bacteria, as well as a comparable minimum inhibitory concentration level to levofloxacin alone. Diabetes was induced in 32 neonatal Sprague-Dawley rats. At 8 weeks of age, rats with blood sugar level >160 were subjected to surgically induced ulcer. Treatment with Val-SLN for 12 days revealed enhanced healing characteristics through cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nitric oxide (NO), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMPs) and vascular endothelial growth factor (VEGF) pathways. Histological examination revealed re-epithelization in Val-SLN treated ulcer, as well as decrease in collagen using trichrome histomorphometric analysis.

Healing capacity of bone marrow mesenchymal stem cells versus platelet-rich fibrin in tibial bone defects of albino rats: an in vivo study.

Background: Various techniques for tissue engineering have been introduced to aid the regeneration of defective or lost bone tissue. The aim of this study was to compare the in vivo bone-forming potential of bone marrow mesenchymal stem cells (BM-MSCs) and platelet-rich fibrin (PRF) on induced bone defects in rats' tibiae. Methods: In total, one defect of 3-mm diameter was created in each tibia of 36 Wistar male rats. There were two groups: group A, left tibia bone defects that received PRF; and group B, right tibia bone defects of the same animal that received BM-MSCs loaded on a chitosan scaffold. Subsequently, Scanning electron microscope/energy-dispersive X-ray (SEM/EDX) analyses was performed at 3 and 10 days, and 3 weeks post­implantation and following euthanasia; (n=12). Results: The EDX analysis performed for each group and time point revealed a significant increase in the mean calcium and phosphorous weight percentage in the BM-MSC-treated group relative to the PRF-treated group at all-time intervals (P < 0.05). Moreover, the mean calcium and phosphorus weight percentage increased as time progressed since the surgical intervention in the PRF-treated and BM-MSCs groups (P < 0.05). Conclusions: In the present study, both BM-MSCs and PRF were capable of healing osseous defects induced in a rat tibial model. Yet, BM-MSCs promoted more adequate healing, with higher mean calcium and phosphorous weight percentages than PRF at all-time points, and showed greater integration into the surrounding tissues than PRF.