Hydrophobic amino acids grafted onto chitosan: a novel amphiphilic chitosan nanocarrier for hydrophobic drugs.
OBJECTIVE
The objective of this study is to develop a novel biocompatible amphiphilic drug delivery for hydrophobic drugs, chitosan (CS) was grafted to a series of hydrophobic amino acids including l-alanine (A), l-proline (P), and l-tryptophan (W) by carbodiimide mediated coupling reaction.


METHODS
Chemical characteristics of the modified polymers were determined and confirmed by FT-IR,1H NMR, and UV-vis spectroscopy and the degree of substitution was quantified by elemental analysis. The modified polymers were used to form amphiphilic chitosan nanocarriers (ACNs) by the conventional self-assembly method using ultrasound technique. The morphology and the size of ACNs were analyzed by scanning electron microscope (SEM) and Dynamic light scattering (DLS).


CONCLUSIONS
The sizes of spherical ACNs analyzed by SEM were obviously smaller than those of determined by DLS. The ACNs effectively surrounded the hydrophobic model drug, letrozole (LTZ), and demonstrated different encapsulation efficiencies (EE), loading capacities (LC), and controlled drug release profiles. The characteristics of ACNs and the mechanism of drug encapsulation were confirmed by molecular modeling method. The modeling of the structures of LTZ, profiles of A, P, and W grafted onto CS and the wrapping process around LTZ was performed by quantum mechanics (QM) methods. There was a good agreement between the experimental and theoretical results. The cell viability was also evaluated in two cell lines compared with free drug by MTT assay.


CONCLUSIONS
The hydrophobic portion effects on ACNs' characteristics and the proper selection of amino acid demonstrate a promising potential for drug delivery vector.
a Department of Biology, Faculty of Science , Razi University , Kermanshah , Islamic Republic of Iran.
Marjan
M
Motiei
b Faculty of Chemistry, Sensor and Biosensor Research Center (SBRC) & Nanoscience and Nanotechnology Research Center (NNRC) , Razi University , Kermanshah , Islamic Republic of Iran.|c Nano Drug Delivery Research Center , Kermanshah University of Medical Sciences , Kermanshah , Islamic Republic of Iran.
Soheila
S
Kashanian
d Department of Organic Chemistry, Chemistry Faculty , Razi University , Kermanshah , Islamic Republic of Iran.|e Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Islamic Republic of Iran.
Avat Arman
AA
Taherpour
D000596:Amino Acids / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D048271:Chitosan / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D053758:Nanoparticles / Q000008:administration & dosage / Q000032:analysis / Q000737:chemistry*; D016716:PC12 Cells; D010316:Particle Size; D051381:Rats; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
D000596:Amino Acids; D004337:Drug Carriers; D048271:Chitosan
Amphiphilic nanocarrier; controlled release; cytotoxicity; hydrophobic amino acids; letrozole; solubility