Alleviating Neuropathy of Diabetic Foot Ulcer by Co-Delivery of Venlafaxine and Matrix Metalloproteinase Drug-Loaded Cellulose Nanofiber Sheets: Production, in Vitro Characterization and Clinical Trial Publisher Pubmed



Meamar R¹ ; Chegini S¹ ; Varshosaz J¹ ; Aminorroaya A¹ ; Amini M¹ ; Siavosh M¹ Show Affiliations
Source: Pharmacological Reports Published:2021

Abstract

Background: The objective of the present study was co-delivery of venlafaxin (VEN) and doxycycline (DOX), a matrix metalloproteinase inhibitor drug, for alleviating inflammation and neuropathy in diabetic foot ulcer (DFU). Methods: Bacterial cellulose nanofiber sheets (BCNS) were loaded with DOX and VEN and categorized by their loading efficiency, release profiles and ex vivo permeation throughrat skin. The optimized nanofibers were used in patients with DFU to compare with the standard wound care regimen during a 12-week trial. Wound area was measured every 2 weeks. Biochemical parameters and microscopic studies of the skin were examined prior and at the end of the treatment. The Michigan Neuropathy Screening Instrument (MNSI) questionnaire was utilized to assess diabetic neuropathy. Results: The optimum formulation showed loading efficiency of 37.8 ± 1.6% for DOX and 48 ± 1.9% for VEN. Rat skin permeation was 40% for DOX after 7–29 h and 83% for VEN during 105 h. Patients treated with BCNS showed no significant difference in their biochemical parameters before and after intervention. The ulcer size showed faster reduction after 12 weeks in the treatment group compared to the control group. The abnormal responses in the MNSI questionnaire decreased and pain-free walking distance increased significantly in the treatment group compared with the control group (p < 0.001). Microscopic studies of the skin after using nanofibers showed a large number of polymorphonuclear chronic inflammatory cells and formation of new capillary beds. Conclusions: The BCNS loaded with DOX and VEN may expedite healing and reduce neuropathy in the DFU of diabetic patients. Graphic abstract: [Figure not available: see fulltext.] © 2021, Maj Institute of Pharmacology Polish Academy of Sciences.