Journal of Fluorescence

, Volume 28, Issue 5, pp 1127–1142 | Cite as

Papain Loaded Poly(ε-Caprolactone) Nanoparticles: In-silico and In-Vitro Studies

  • Yasemin Budama-Kilinc
  • Rabia Cakir-Koc
  • Serda Kecel-Gunduz
  • Tolga Zorlu
  • Yagmur Kokcu
  • Bilge Bicak
  • Zeynep Karavelioglu
  • Aysen E. Ozel


Papain is a protease enzyme with therapeutic properties that are very valuable for medical applications. Poly(ε-caprolactone) (PCL) is an ideal polymeric carrier for controlled drug delivery systems due to its low biodegradability and its high biocompatibility. In this study, the three-dimensional structure and action mechanism of papain were investigated by in vitro and in silico experiments using molecular dynamics (MD) and molecular docking methods to elucidate biological functions. The results showed that the size of papain-loaded PCL nanoparticles (NPs) and the polydispersity index (PDI) of the NPs were 242.9 nm and 0.074, respectively. The encapsulation efficiency and loading efficiency were 80.4 and 27.2%, respectively. Human embryonic kidney cells (HEK-293) were used for determining the cytotoxicity of papain-loaded PCL and PCL nanoparticles. The in vitro cell culture showed that nanoparticles are not toxic at low concentrations, while toxicity slightly increases at high concentrations. In silico studies, which were carried out with MD simulations and ADME analysis showed that the strong hydrogen bonds between the ligand and the papain provide stability and indicate the regions in which the interactions occur.


Papain Enzyme Fluorescence Imaging PCL HEK-293 Molecular docking Molecular dynamic 



Authors are very thankful Rita Podzuna for allowing to use the docking program with Schrödinger's Small-Molecule Drug Discory Suite.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that there are no conflicts of interest associated with this work.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yasemin Budama-Kilinc
    • 1
  • Rabia Cakir-Koc
    • 1
  • Serda Kecel-Gunduz
    • 2
  • Tolga Zorlu
    • 3
  • Yagmur Kokcu
    • 4
  • Bilge Bicak
    • 2
    • 4
  • Zeynep Karavelioglu
    • 3
  • Aysen E. Ozel
    • 2
  1. 1.Faculty of Chemical and Metallurgical Engineering, Department of BioengineeringYildiz Technical UniversityIstanbulTurkey
  2. 2.Faculty of Science, Physics DepartmentIstanbul UniversityIstanbulTurkey
  3. 3.Graduate School of Natural and Applied ScienceYildiz Technical UniversityIstanbulTurkey
  4. 4.Graduate School of Engineering and SciencesIstanbul UniversityIstanbulTurkey

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