In Vitro Evaluation of Telmisartan Loaded PCL/Collagen Small Diameter Vascular Grafts


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Birer M. , Acartürk F.

12th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology (PBP), Vienna, Austria, 11 - 14 May 2021, pp.1

  • Publication Type: Conference Paper / Full Text
  • City: Vienna
  • Country: Austria
  • Page Numbers: pp.1

Abstract

INTRODUCTION Telmisartan (TEL) is a well-known angiotensin II receptor blocker. Poly(ε-caprolactone) (PCL) is an FDA approved polymer and collagen (COL) is the main component of vascular extracellular matrix. Both of them are widely used in scaffolds. Electrospinning is an effective method to obtain nano-sized scaffolds [1]. AIM The aim of this study was to prepare telmisartan loaded small diameter PCL/COL vascular grafts with electrospinning method. MATERIALS Telmisartan is kindly donated by Nobel Pharmaceuticals (Düzce, Turkey). Collagen (Type I from calf skin), PCL (mw: 80.000), hexafluoroisopropanol (HFIP), acetic acid and chloroform are purchased from Sigma Aldrich (Missouri, USA). METHODS In order to perform electrospinning COL, TEL and PCL were dissolved in a mixture of HFIP:acetic acid:chloroform (2.5,1.5:1). Viscosity, conductivity and surface tension values of the prepared solutions were measured. Electrospinning process was performed INOVENSO NE300 electrospinner (Inovenso, Turkey) with a 3 mm rod collector. Differential scanning calorimetry (DSC) thermograms, Fourier-Transform Infrared (FT-IR) and Xray diffraction spectra of raw materials and electrospun grafts. Mechanical characterization studies of the grafts were performed with tensile strength, Young modulus and elongation at break measurements. The morphology of the nanofibers was evaluated with a scanning electron microscope (SEM). Formulations were selected by means of mechanical results. TEL dissolution from selected formulations were investigated. In vitro dissolution study was performed with an Erlenmeyer flask with a 6 cm magnetic stirrer 50 rpm rotation speed in a water bath adjusted at 37 oC for 21 days.

Solution Characterization All polymer solutions were found to be suitable for electrospinning. Solution characterization study results were given in Table 1. Electrospinning process and Mechanical Characterization studies All fibers were successfully produced with fibrous structures It was not found any incompatibilities according to DSC thermograms, XRD and FT-IR spectra. Formulations F15, F16 and F17 were bilayered and rotation speed of collector was 3000 and 2000 rpm for inner and outer sections of grafts, respectively. All other grafts were produced with 2000 rpm rotation speed. Distance was 14 cm for all formulations. Voltage and flow rate was varied between 11-21 kV and 1.5-3.5 mL/h, respectively. Mechanical characterization results of electrospun vascular grafts were given in Table 2. Formulations F15, F16 and F17 were found to be suitable for to use as vascular graft by means of mechanical properties. In vitro Dissolution Studies Dissolution study of TEL from bilayered grafts were performed. Results of dissolution study are given in Figure 1. CONCLUSION Prepared polymer solution properties were suitable for electrospinning and formulations were successfully electrospun. It can be said that HFIP:acetic acid:chloroform is a suitable solvent system for the electrospinning PCL/Collagen blend. TEL loaded vascular grafts were successfully prepared. In vitro release of formulations were controlled and release continued to the end of 21 days. Electrospinning is a promising method for drug loaded small diameter vascular graft production. REFERENCE 1.Tillman BW, Yazdani SK, Lee SJ, Geary RL, Atala A, Yoo JJ. The in vivo stability of electrospun polycaprolactone-collagen scaffolds in vascular reconstruction. Biomaterials. 30, 583–588. (2009). ACKNOWLEDGEMENT This study was supported by Gazi University, Projects of Scientific Investigation under the project number: 02/2019- 04.