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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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