Publications by authors named "Niyousha Rafiee Tehrani"

7 Publications

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Novel chitosan based nanoparticles as gene delivery systems to cancerous and noncancerous cells.

Int J Pharm 2019 Apr 20;560:306-314. Epub 2019 Feb 20.

Departments of Pharmaceutics and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

The present study aimed to investigate in vitro DNA transfection efficiency of three novel chitosan derivatives: thiolated trimethyl chitosan (TMC-Cys), methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan(MABCC) and thiolated trimethyl aminobenzyl chitosan(MABC-Cys). After polymer synthesis and characterization, nanoparticles were prepared using these polymers and their size, zeta potential and DNA condensing ability were measured. After that, cytotoxicity and transfection efficiency of nanocomplexes were carried out in three different cells. The results showed that all polymers could condense DNA plasmid strongly from N/P 2 and nanocomplexes had eligible sizes and zeta potentials. Moreover, the nanocomplexes had negligible cytotoxicity and MABC-Cys was the most effective vehicle for gene delivery in HEK-293T cells. In the two other cell lines, SKOV-3 and MCF-7, TMC-Cys exhibited the highest transfection efficiency. This study indicated that chemical structure of these novel chitosan derivatives in the interaction with the cell type can lead to successful gene delivery.
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http://dx.doi.org/10.1016/j.ijpharm.2019.02.016DOI Listing
April 2019

Synthesis and characterization of a novel peptide-grafted Cs and evaluation of its nanoparticles for the oral delivery of insulin, in vitro, and in vivo study.

Int J Nanomedicine 2018 6;13:5127-5138. Epub 2018 Sep 6.

Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran,

Background: Despite years of experience and rigorous research, injectable insulin is the sole trusted treatment method to control the blood glucose level in diabetes type 1 patients, but injection of insulin is painful and poses a lot of stress to the patients, especially children, therefore, development of a non-injectable formulation of insulin is a major breakthrough in the history of medicine and pharmaceutical sciences.

Methods: In this study, a novel peptide grafted derivative of chitosan (CPP-g- chitosan) is synthesized and its potential for oral delivery of proteins and peptides is evaluated. Drug-loaded nanoparticles were developed from this derivative using ionic gelation method with application of sodium tripolyphosphate (TPP) as a cross-linking agent. Human insulin was used as the model protein drug and release kinetic was studied at gastrointestinal pH. Finally the developed nanoparticles were filled into very tiny enteric protective capsules and its effects on blood glucose level are evaluated in laboratory animals.

Results: Presence of the positively charged cell-penetrating peptide moiety in the structure of chitosan polymer had slight inhibitory effects on the release of insulin from the nanoparticles in simulated gastric fluid (pH 1.2) comparing to native chitosan. The nanoparticles were positively charged in gastrointestinal pH with size ranging from 180 nm to 326 nm. The polypeptide grafted to chitosan is a novel analog of Penetratin, presenting both the hydrophilic and hydrophobic characteristics altering the release behavior of the nanoparticles and significantly increase the absorption of insulin into the rat epithelium comparing to nanoparticles from simple chitosan. In-vivo results in diabetic rat proved that this nanoparticulate system can significantly lower the blood glucose levels in diabetic rats and remain effective for a duration of 9-11 hours.

Conclusion: The results indicate that nanoparticles developed from this new peptide conjugated derivative of chitosan are very promising for oral delivery of proteins and peptides.
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http://dx.doi.org/10.2147/IJN.S161240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135219PMC
October 2018

Determination of diffusion coefficient for released nanoparticles from developed gelatin/chitosan bilayered buccal films.

Int J Biol Macromol 2018 Jun 26;112:1005-1013. Epub 2018 Feb 26.

Institute of Biochemistry & Biophysics (IBB), University of Tehran, Tehran, Iran.

This study aims at the mathematical optimization by Box-Behnken statistical design, fabrication by ionic gelation technique and in vitro characterization of insulin nanoparticles containing thiolated N- dimethyl ethyl chitosan (DMEC-Cys) conjugate. Then Optimized insulin nanoparticles were loaded into the buccal film, and in-vitro drug release from films was investigated, and diffusion coefficient was predicted. The optimized nanoparticles were shown to have mean particle size diameter of 148nm, zeta potential of 15.5mV, PdI of 0.26 and AE of 97.56%. Cell viability after incubation with optimized nanoparticles and films were assessed using an MTT biochemical assay. In vitro release study, FTIR and cytotoxicity also indicated that nanoparticles made of this thiolated polymer are suitable candidates for oral insulin delivery.
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http://dx.doi.org/10.1016/j.ijbiomac.2018.01.215DOI Listing
June 2018

New comprehensive mathematical model for HPMC-MCC based matrices to design oral controlled release systems.

Eur J Pharm Biopharm 2017 Dec 22;121:61-72. Epub 2017 Sep 22.

School of Pharmacy, Tehran University of Medical Science, Iran.

A comprehensive model with all effective phenomena in drug release such as diffusion, swelling and erosion was considered. In this work, a mathematical model was developed to describe drug release from controlled release HPMC matrices as a favorable system in pharmaceutical industries. As a novel study, the impact of the MCC presence as a filler in tablet preparation process was considered in the mathematical model. In addition, we found that the volume expansion of these polymeric matrices did not follow the ideal mixing rule and we derived an equation for estimating the volume of hydrated matrix. Furthermore, some equations were derived to estimate the parameters of model (K, D) as well as the change in matrix volume based on the amount of polymer and filler in formulation. This investigation gave deeper insight into underlying drug release mechanisms. According to the results, K increases linearly and D increases exponentially with the increase in the amount of MCC in formulation. Application of this comprehensive mathematical model enables us to predict the behavior of HPMC-MCC based matrices. Furthermore, this model is able to represent the formulation for the desired drug release profile which is useful to design new controlled release matrix as well as improving the system geometry and dimensions of tablets. The presented model was validated by two independent tests: (a) predicting the behavior of matrix with certain MCC/HPMC ratio upon exposure to the release medium; (b) designing formulation of Bupropion hydrochloride extended release tablet.
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http://dx.doi.org/10.1016/j.ejpb.2017.09.007DOI Listing
December 2017

A novel nanoemulsion-based method to produce ultrasmall, water-dispersible nanoparticles from chitosan, surface modified with cell-penetrating peptide for oral delivery of proteins and peptides.

Int J Nanomedicine 2017 2;12:3471-3483. Epub 2017 May 2.

Department of Pharmaceutics.

A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as "nano-containers and nano-reactors". The entrapped polymer chains of CS inside these "nano-reactors" are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP) is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin) is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%-19% increase), and animal studies are actively under progress and will be published separately.
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http://dx.doi.org/10.2147/IJN.S116063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422456PMC
August 2017

Thiolated methylated dimethylaminobenzyl chitosan: A novel chitosan derivative as a potential delivery vehicle.

Int J Biol Macromol 2017 Feb 17;95:574-581. Epub 2016 Nov 17.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Chitosan is a natural mucoadhesive, biodegradable, biocompatible and nontoxic polymer which has been used in pharmaceutical industry for a lot of purposes such as dissolution enhancing, absorption enhancing, sustained releasing and protein, gene or drug delivery. Two major disadvantages of chitosan are poor solubility in physiological pH and low efficiency for protein and gene delivery. In this study thiolated methylated N-(4-N,N-dimethylaminobenzyl) chitosan was prepared for the first time in order to improve the solubility and delivery properties of chitosan. This novel chitosan derivative was characterized using H NMR, Ellman test, TGA and Zetasizer. Cell toxicity studies were performed on Human Embryonic Kidney 293 (Hek293) cell line using XTT method, to investigate the potential effect of this new derivative on cell viability. H NMR results showed that all substitution reactions were successfully carried out. Zeta potential of new derivative at acidic and physiological pHs was greater than chitosan and it revealed an increase in solubility of the derivative. Furthermore, it had no significant cytotoxicity against Hek293 cell line in comparison to chitosan. These findings confirm that this new derivative can be introduced as a suitable compound for biomedical purposes.
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http://dx.doi.org/10.1016/j.ijbiomac.2016.10.094DOI Listing
February 2017

Methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan as a new chitosan derivative: Synthesis, characterization, cytotoxicity and antibacterial activity.

Carbohydr Polym 2016 09 28;149:131-9. Epub 2016 Apr 28.

Departments of Pharmaceutics and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Chitosan, as a biocompatible polymer, is very attractive for biomedical applications. Continues studies are performing for improving its physicochemical features in order to make it more suitable for such approaches. In this study, methylated 4-N,N dimethyl aminobenzyl N,O carboxymethyl chitosan (MABCC) was synthesized,as a new chitosan derivative, in three steps. The investigations were carried out using FTIR, NMR, TGA and zeta potential measurement. Antibacterial and cell viability assessments were performed on four bacterial strains and two cell lines respectively. FTIR and NMR results showed that all substitution reactions were successfully carried out. Zeta potential of MABCC at various pH especially alkaline pH was greater than chitosan and it revealed increasing the solubility of the derivative. Antibacterial activity of MABCC was extremely greater than chitosan especially in Gram positive bacteria.Furthermore,it had no significant cytotoxicity against MCF-7 and Skov-3 cell lines in comparison to chitosan. These findings confirm that this new derivative can be introduced as a suitable compound for biomedical purposes.
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http://dx.doi.org/10.1016/j.carbpol.2016.04.116DOI Listing
September 2016
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