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

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2019 Mar 10

PMID 30850895

Citations 5

Authors

Abbas Hemati Azandaryani

Soheila Kashanian

Mohsen Shahlaei

Katayoun Derakhshandeh

Marjan Motiei

Sajad Moradi

Affiliations

Soon will be listed here.

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 IC 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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References

Haynes B, Dowsett M, Miller W, Dixon J, Bhatnagar A . The pharmacology of letrozole. J Steroid Biochem Mol Biol. 2003; 87(1):35-45. DOI: 10.1016/s0960-0760(03)00384-4. View

Macedo L, Guo Z, Tilghman S, Sabnis G, Qiu Y, Brodie A . Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Res. 2006; 66(15):7775-82. DOI: 10.1158/0008-5472.CAN-05-3984. View

Reis C, Neufeld R, Ribeiro A, Veiga F . Nanoencapsulation I. Methods for preparation of drug-loaded polymeric nanoparticles. Nanomedicine. 2007; 2(1):8-21. DOI: 10.1016/j.nano.2005.12.003. View

Westerink R, Ewing A . The PC12 cell as model for neurosecretion. Acta Physiol (Oxf). 2007; 192(2):273-85. PMC: 2663028. DOI: 10.1111/j.1748-1716.2007.01805.x. View

Mondal N, Pal T, Ghosal S . Development, physical characterization, micromeritics and in vitro release kinetics of letrozole loaded biodegradable nanoparticles. Pharmazie. 2008; 63(5):361-5. View

Yoksan R, Jirawutthiwongchai J, Arpo K . Encapsulation of ascorbyl palmitate in chitosan nanoparticles by oil-in-water emulsion and ionic gelation processes. Colloids Surf B Biointerfaces. 2009; 76(1):292-7. DOI: 10.1016/j.colsurfb.2009.11.007. View

Xia Y, Nguyen T, Yang M, Lee B, Santos A, Podsiadlo P . Self-assembly of self-limiting monodisperse supraparticles from polydisperse nanoparticles. Nat Nanotechnol. 2011; 6(9):580-7. DOI: 10.1038/nnano.2011.121. View

Dixit P, Jain D, Dumbwani J . Standardization of an ex vivo method for determination of intestinal permeability of drugs using everted rat intestine apparatus. J Pharmacol Toxicol Methods. 2011; 65(1):13-7. DOI: 10.1016/j.vascn.2011.11.001. View

Ridolfi D, Marcato P, Justo G, Cordi L, Machado D, Duran N . Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin. Colloids Surf B Biointerfaces. 2012; 93:36-40. DOI: 10.1016/j.colsurfb.2011.11.051. View

10.

Silva A, Amaral M, Gonzalez-Mira E, Santos D, Ferreira D . Solid lipid nanoparticles (SLN)--based hydrogels as potential carriers for oral transmucosal delivery of risperidone: preparation and characterization studies. Colloids Surf B Biointerfaces. 2012; 93:241-8. DOI: 10.1016/j.colsurfb.2012.01.014. View

11.

Derakhshandeh K, Fathi S . Role of chitosan nanoparticles in the oral absorption of Gemcitabine. Int J Pharm. 2012; 437(1-2):172-7. DOI: 10.1016/j.ijpharm.2012.08.008. View

12.

Mandal B, Bhattacharjee H, Mittal N, Sah H, Balabathula P, Thoma L . Core-shell-type lipid-polymer hybrid nanoparticles as a drug delivery platform. Nanomedicine. 2012; 9(4):474-91. DOI: 10.1016/j.nano.2012.11.010. View

13.

Afshari M, Derakhshandeh K, Hosseinzadeh L . Characterisation, cytotoxicity and apoptosis studies of methotrexate-loaded PLGA and PLGA-PEG nanoparticles. J Microencapsul. 2013; 31(3):239-45. DOI: 10.3109/02652048.2013.834991. View

14.

Ahmad Panahi H, Reza Soltani E, Moniri E, Tamadon A . Synthesis and characterization of poly[1-(N,N-bis-carboxymethyl)amino-3-allylglycerol-co-dimethylacrylamide] grafted to magnetic nano-particles for extraction and determination of letrozole in biological and pharmaceutical samples. Talanta. 2013; 117:511-7. DOI: 10.1016/j.talanta.2013.09.015. View

15.

Siddiqa A, Chaudhury K, Adhikari B . Letrozole dispersed on poly (vinyl alcohol) anchored maleic anhydride grafted low density polyethylene: a controlled drug delivery system for treatment of breast cancer. Colloids Surf B Biointerfaces. 2014; 116:169-75. DOI: 10.1016/j.colsurfb.2013.12.040. View

16.

Rostami E, Kashanian S, Azandaryani A . Preparation of solid lipid nanoparticles as drug carriers for levothyroxine sodium with in vitro drug delivery kinetic characterization. Mol Biol Rep. 2014; 41(5):3521-7. DOI: 10.1007/s11033-014-3216-4. View

17.

Rostami E, Kashanian S, Azandaryani A, Faramarzi H, Ezzati Nazhad Dolatabadi J, Omidfar K . Drug targeting using solid lipid nanoparticles. Chem Phys Lipids. 2014; 181:56-61. DOI: 10.1016/j.chemphyslip.2014.03.006. View

18.

Ding Y, Shen S, Sun H, Sun K, Liu F, Qi Y . Design and construction of polymerized-chitosan coated Fe3O4 magnetic nanoparticles and its application for hydrophobic drug delivery. Mater Sci Eng C Mater Biol Appl. 2015; 48:487-98. DOI: 10.1016/j.msec.2014.12.036. View

19.

Luo Y, Teng Z, Li Y, Wang Q . Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake. Carbohydr Polym. 2015; 122:221-9. DOI: 10.1016/j.carbpol.2014.12.084. View

20.

Stigliani M, Haghi M, Russo P, Young P, Traini D . Antibiotic transport across bronchial epithelial cells: Effects of molecular weight, LogP and apparent permeability. Eur J Pharm Sci. 2015; 83:45-51. DOI: 10.1016/j.ejps.2015.12.010. View