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Folate Conjugated Hybrid Nanocarrier for Targeted Letrozole Delivery in Breast Cancer Treatment

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Abstract

Purpose

Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer – lipid hybrid nanoparticles – is introduced for cancer treatment.

Methods

Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation. The physicochemical characterization in vitro drug release, cytotoxicity, and then ex vivo study of obtained carrier was investigated.

Results

Both thermal and crystallography studies proved the amorphous loading of drug in the nanocarrier. The cytotoxicity investigation with an average IC50 value of 79 ± 2.40 nM proved the efficiency of the coupled folic acid carrier for the intracellular uptake of letrozole on the breast cancer line. Ex vivo, the study proved the positive effect of the letrozole entrapment on the drug bioavailability.

Conclusions

The obtained targeted nanocarrier could overcome the limitations associated with the LTZ as a potent non-steroidal drug. Both the entrapment and therapeutic efficiency of letrozole in the amphiphilic carrier were increased using the lipid nanoparticles and the surface modification, respectively.

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Abbreviations

CS :

Chitosan

DCM :

Dichloromethane

DSC :

Differential scanning calorimetric

DL :

Drug loading

EDC :

1-Ethyl-3-(3-dimethylaminopropyl

EE :

Entrapment efficiency

FA:

Folic acid

FA-PLNs:

FA coupled PLNs

FT-IR :

Fourier transform infrared spectroscopy

IC 50 :

Half-maximal inhibitory concentration

K :

Dissolution rate constant

LTZ :

Letrozole

MTT :

3-(4,5-dimethyl- thiazol-2yl)-2,5-diphenyltetrazoliumbromide

NDDSs:

Nano drug delivery systems

NHS :

N-Hydroxysuccinimide

NPs :

Nanoparticles

Papp :

Apparent permeability coefficients

PBS :

Phosphate buffered saline

PCS :

Photon correlation spectroscopy

PDI :

Polydispersity index

PLNs:

Polymer – lipid hybrid nanocarriers

R 2 :

Correlation coefficient

SA :

Stearic acid

SEM :

Scanning electron microscopy

SPSS :

Statistical package for the social sciences software

TPG :

Tripalmitin glyceride

TPP :

Pentasodium tripolyphosphate

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Authors and Affiliations

  1. Department of Applied Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran

    Abbas Hemati Azandaryani & Soheila Kashanian

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

    Abbas Hemati Azandaryani & Soheila Kashanian

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

    Katayoun Derakhshandeh

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

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Hemati Azandaryani, A., Kashanian, S. & Derakhshandeh, K. Folate Conjugated Hybrid Nanocarrier for Targeted Letrozole Delivery in Breast Cancer Treatment. Pharm Res 34, 2798–2808 (2017). https://doi.org/10.1007/s11095-017-2260-x

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  • DOI: https://doi.org/10.1007/s11095-017-2260-x

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