Pharmaceutical Research

, 36:62 | Cite as

A Comprehensive Physicochemical, In Vitro and Molecular Characterization of Letrozole Incorporated Chitosan-Lipid Nanocomplex

  • Abbas Hemati Azandaryani
  • Soheila KashanianEmail author
  • Mohsen Shahlaei
  • Katayoun Derakhshandeh
  • Marjan Motiei
  • Sajad Moradi
Research Paper



The aim of this study is to show a new mesomicroscopic insight into Letrozole (LTZ) loaded nanocomplexes and their ex vivo characteristics as a drug delivery system.


The LTZ loaded hybrid chitosan-based carrier was fabricated using a modified ionic crosslinking technique and characterized in more detail. To understand the mechanism of LTZ action encapsulated in the hybrid polymer-lipid carrier, all-atom molecular dynamics simulations were also used.


The physicochemical properties of the carrier demonstrated the uniform morphology, but different drug loading ratios. In vitro cytotoxic activity of the optimized carrier demonstrated IC50 of 67.85 ± 0.55 nM against breast cancer cell line. The ex vivo study showed the positive effect of nanocomplex on LTZ permeability 7–10 fold greater than the free drug. The molecular dynamic study also confirmed the prsence of hydrophobic peak of lipids at a distance of 5 Å from the center of mass of LTZ which proved drug entrapment in the core of nanocomplex.


The hybrid nanoparticle increased the cytotoxicity and tissue permeability of LTZ for oral delivery. This study also confirmed the atomic mesostructures and interaction of LTZ in the core of hybrid polymer-lipid nanoparticles.

Key Words

chitosan-lipid nanocomplex letrozole molecular dynamics PLN, aromatase inhibitor, non-everted sac study 



Center of mass




Differential scanning calorimetric


Entrapment efficiency


Fourier transform infrared spectroscopy




Half-maximal inhibitory concentration


Dissolution rate constant


Loading capacity




Molecular dynamics


3-(4,5-dimethyl- thiazol-2yl)-2,5-diphenyltetrazolium bromide




Apparent permeability coefficients


Phosphate buffered saline


Photon correlation spectroscopy


Polydispersity index




Polymer – lipid hybrid nanoparticle


Correlation coefficient


Root mean square deviation


Relative standard deviation


Stearic acid


Solvent accessible surface area


Standard deviation


Scanning electron microscopy


Simulated gastric fluid


Simulated intestinal fluid


Solid lipid nanoparticles


Statistical package for the social sciences software


Tripalmitin glyceride


Pentasodium tripolyphosphate



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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Abbas Hemati Azandaryani
    • 1
    • 2
  • Soheila Kashanian
    • 1
    • 2
    Email author
  • Mohsen Shahlaei
    • 1
  • Katayoun Derakhshandeh
    • 3
  • Marjan Motiei
    • 4
  • Sajad Moradi
    • 1
  1. 1.Nano Drug Delivery Research CenterKermanshah University of Medical SciencesKermanshahIran
  2. 2.Department of Applied Chemistry, Faculty of ChemistryRazi UniversityKermanshahIran
  3. 3.Department of Pharmaceutics, Faculty of PharmacyHamedan University of Medical SciencesHamedanIran
  4. 4.Centre of Polymer SystemsTomas Bata University in ZlinZlínCzech Republic

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