A doxycycline-loaded microfiber of poly-metformin/PCL for eradicating melanoma stem cells

Int J Pharm. 2024 Jul 20:660:124358. doi: 10.1016/j.ijpharm.2024.124358. Epub 2024 Jun 17.

Abstract

Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC50 of PolyMet/PCL@DOX was 7.4 μg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.

Keywords: CD44 expression; Cancer stem cells; Doxycycline; Microfibers surgery patch; Polycaprolactone; Polymetformin.

MeSH terms

  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Doxycycline* / administration & dosage
  • Doxycycline* / chemistry
  • Doxycycline* / pharmacology
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Drug Liberation*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Melanoma* / drug therapy
  • Melanoma* / pathology
  • Metformin / administration & dosage
  • Metformin / chemistry
  • Metformin / pharmacology
  • Neoplastic Stem Cells* / drug effects
  • Polyesters* / chemistry
  • Porosity

Substances

  • Doxycycline
  • Polyesters
  • polycaprolactone
  • Metformin
  • Hyaluronan Receptors
  • Drug Carriers
  • CD44 protein, human
  • Antineoplastic Agents