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

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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.

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Abbreviations

COM :

Center of mass

CS :

Chitosan

DSC :

Differential scanning calorimetric

EE :

Entrapment efficiency

FT-IR :

Fourier transform infrared spectroscopy

GI :

Gastrointestinal

IC 50 :

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

R 2 :

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

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Authors and Affiliations

  1. Nano Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, 6734667149, Iran

    Abbas Hemati Azandaryani, Soheila Kashanian, Mohsen Shahlaei & Sajad Moradi

  2. Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, 6714967346, Iran

    Abbas Hemati Azandaryani & Soheila Kashanian

  3. Department of Pharmaceutics, Faculty of Pharmacy, Hamedan University of Medical Sciences, Hamedan, 6517838678, Iran

    Katayoun Derakhshandeh

  4. Centre of Polymer Systems, Tomas Bata University in Zlin, Tr. Tomase Bati 5678, 760 01, Zlín, Czech Republic

    Marjan Motiei

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  1. Abbas Hemati Azandaryani
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  2. Soheila Kashanian
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  4. Katayoun Derakhshandeh
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Correspondence to Soheila Kashanian.

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Azandaryani, A.H., Kashanian, S., Shahlaei, M. et al. A Comprehensive Physicochemical, In Vitro and Molecular Characterization of Letrozole Incorporated Chitosan-Lipid Nanocomplex. Pharm Res 36, 62 (2019). https://doi.org/10.1007/s11095-019-2597-4

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