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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
  • 97 Downloads

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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 

Abbreviations

COM

Center of mass

CS

Chitosan

DSC

Differential scanning calorimetric

EE

Entrapment efficiency

FT-IR

Fourier transform infrared spectroscopy

GI

Gastrointestinal

IC50

Half-maximal inhibitory concentration

K

Dissolution rate constant

LC

Loading capacity

LTZ

Letrozole

MD

Molecular dynamics

MTT

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

NPs

Nanoparticles

Papp

Apparent permeability coefficients

PBS

Phosphate buffered saline

PCS

Photon correlation spectroscopy

PDI

Polydispersity index

P-gp

P-glycoprotein

PLN

Polymer – lipid hybrid nanoparticle

R2

Correlation coefficient

RMSD

Root mean square deviation

RSD

Relative standard deviation

SA

Stearic acid

SASA

Solvent accessible surface area

SD

Standard deviation

SEM

Scanning electron microscopy

SGF

Simulated gastric fluid

SIF

Simulated intestinal fluid

SLNs

Solid lipid nanoparticles

SPSS

Statistical package for the social sciences software

TPG

Tripalmitin glyceride

TPP

Pentasodium tripolyphosphate

Notes

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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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