Publications by authors named "Leila Rezaie Shirmard"

6 Publications

  • Page 1 of 1

Improving the biological activity of fingolimod loaded PHBV nanoparticles by using hydrophobically modified alginate.

Drug Dev Ind Pharm 2020 Feb 6;46(2):318-328. Epub 2020 Feb 6.

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

Uncontrolled distribution of nanoparticles (NPs) within the body can significantly decrease the efficiency of drug therapy and is considered among the main restrictions of NPs application. The aim of this study was to develop a depot combination delivery system (CDS) containing fingolimod loaded poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) NPs dispersed into a matrix of oleic acid-grafted-aminated alginate (OA-g-AAlg) to minimize the nonspecific biodistribution (BD) of PHBV NPs. OA-g-AAlg was synthesized in two step; First, Alg was aminated by using adipic dihydrazide (ADH). The degree of hyrazide group substitution of Alg was determined by trinitro-benzene-sulfonic acid (TNBS) assay. Second, OA was attached to AAlg through formation of an amide bond. Chemical structure of OA-g-AAlg was confirmed with FTIR and HNMR spectroscopy. Furthermore, rheological properties of OA-g-AAlg with different grafting ratios were evaluated. release studies indicated that 47% of fingolimod was released from the CDS within 28 days. Blood and tissue samples were analyzed using liquid chromatography/tandem mass spectrometry following subcutaneous (SC) injection of fingolimod-CDS into Wistar rats. The elimination phase half-life of CDS-fingolimod was significantly higher than that of fingolimod (∼32 d vs. ∼20 h). To investigate the therapeutic efficacy, lymphocyte count was assessed over a 40 day period in Wistar rats. Peripheral blood lymphocyte count decreased from baseline by 27 ± 8% in 2 days after injection. Overall, the designed CDS represented promising results in improving the pharmacokinetic properties of fingolimod. Therefore, we believe that this sustained release formulation has a great potential to be applied to delivery of various therapeutics.
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http://dx.doi.org/10.1080/03639045.2020.1721524DOI Listing
February 2020

Development of Octreotide-Loaded Chitosan and Heparin Nanoparticles: Evaluation of Surface Modification Effect on Physicochemical Properties and Macrophage Uptake.

J Pharm Sci 2019 09 10;108(9):3036-3045. Epub 2019 May 10.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-645, Tehran, Iran. Electronic address:

Octreotide (OCT) is a therapeutic peptide which is administered for the treatment of acromegaly. The purpose of this study was to design a new polyethylene glycol (PEG)-conjugated nanoparticle (PEG-NP) to overcome the short half-life and poor stability of OCT. The developed PEG-NPs were compared with non-PEGylated NPs with respect to their size, morphological characteristics, loading efficiency, release profile, and macrophage uptake. The OCT-loaded NPs and PEG-NPs were prepared by ionic complexion of chitosan (Cs) with either heparin (Hp) or PEGylated heparin (PEG-Hp). The chemical structure of PEG-Hp was confirmed by IR and proton nuclear magnetic resonance. Morphological analyses by scanning electron microscopy showed that NPs and PEG-NPs have a uniform shape. Dynamic laser scattering measurements indicated that hydrodynamic diameter of NPs and PEG-NPs were 222.5 ± 10.0 nm and 334.9 ± 6.7 nm, respectively. NPs and PEG-NPs had a positive zeta potential of about 32.5 ± 1.1 mv and 20.6 ± 2.4 mv, respectively. Entrapment efficiency was 61.4 ± 1.0% and 55.7 ± 2.4% for NPs and PEG-NPs, respectively. Compared with the NPs, the PEG-NPs exhibited a slower release profile. Subsequently, fluorescein isothiocyanate-labeled chitosanCs was synthesized and used to evaluate the stealth characteristic of PEG-NPs. In vitro macrophage uptake of fluorescently labeled NPs was measured by flow cytometry.
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http://dx.doi.org/10.1016/j.xphs.2019.05.002DOI Listing
September 2019

Preparation, characterization and in vivo evaluation of a combination delivery system based on hyaluronic acid/jeffamine hydrogel loaded with PHBV/PLGA blend nanoparticles for prolonged delivery of Teriparatide.

Eur J Pharm Sci 2017 Apr 13;101:167-181. Epub 2017 Feb 13.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Medical Biomaterial Research Centre (MBRC), Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

In the current study, biodegradable PHBV/PLGA blend nanoparticles (NPs) containing Teriparatide were loaded in hyaluronic acid/jeffamine (HA-JEF ED-600) hydrogel to prepare a combination delivery system (CDS) for prolonged delivery of Teriparatide. The principal purpose of the present study was to formulate an effective and prolonged Teriparatide delivery system in order to reduce the frequency of injection and thus enhance patient's compliance. Morphological properties, swelling behaviour, crosslinking efficiency and rheological characterization of HA-JEF ED-600 hydrogel were evaluated. The CDS was acquired by adding PHBV/PLGA NPs to HA-JEF ED-600 hydrogel simultaneously with crosslinking reaction. The percentage of NPs incorporation within the hydrogel as well as the loading capacity and morphology of Teriparatide loaded CDS were examined. Intrinsic fluorescence and circular dichroism spectroscopy proved that Teriparatide remains stable after processing. The release profile represented 63% Teriparatide release from CDS within 50days with lower burst release compared to NPs and hydrogel. MTT assay was conducted by using NIH3T3 cell line and no sign of reduction in cell viability was observed. Based on Miller and Tainter method, LD of Teriparatide loaded CDS was 131.8mg/kg. In vivo studies demonstrated that Teriparatide loaded CDS could effectively increase serum calcium level after subcutaneous injection in mice. Favourable results in the current study introduced CDS as a promising candidate for controlled delivery of Teriparatide and pave the way for future investigations in the field of designing prolonged delivery systems for other peptides and proteins.
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http://dx.doi.org/10.1016/j.ejps.2017.02.018DOI Listing
April 2017

Application of Artificial Neural Networks in the Design and Optimization of a Nanoparticulate Fingolimod Delivery System Based on Biodegradable Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate).

J Pharm Sci 2017 01 22;106(1):176-182. Epub 2016 Sep 22.

Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Medical Biomaterials Research Center (MBRC), Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Formulation of a nanoparticulate Fingolimod delivery system based on biodegradable poly(3-hydroxybutyrate-co-3-hydroxyvalerate) was optimized according to artificial neural networks (ANNs). Concentration of poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PVA and amount of Fingolimod is considered as the input value, and the particle size, polydispersity index, loading capacity, and entrapment efficacy as output data in experimental design study. In vitro release study was carried out for best formulation according to statistical analysis. ANNs are employed to generate the best model to determine the relationships between various values. In order to specify the model with the best accuracy and proficiency for the in vitro release, a multilayer percepteron with different training algorithm has been examined. Three training model formulations including Levenberg-Marquardt (LM), gradient descent, and Bayesian regularization were employed for training the ANN models. It is demonstrated that the predictive ability of each training algorithm is in the order of LM > gradient descent > Bayesian regularization. Also, optimum formulation was achieved by LM training function with 15 hidden layers and 20 neurons. The transfer function of the hidden layer for this formulation and the output layer were tansig and purlin, respectively. Also, the optimization process was developed by minimizing the error among the predicted and observed values of training algorithm (about 0.0341).
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http://dx.doi.org/10.1016/j.xphs.2016.07.026DOI Listing
January 2017

Preparation, statistical optimisation and in vitro characterisation of poly (3-hydroxybutyrate-co-3-hydroxyvalerate)/poly (lactic-co-glycolic acid) blend nanoparticles for prolonged delivery of teriparatide.

J Microencapsul 2016 Aug 17;33(5):460-474. Epub 2016 Jul 17.

a Faculty of Pharmacy, Department of Pharmaceutics , Tehran University of Medical Sciences , Tehran , Iran (the Islamic Republic of).

The purpose of this study was the preparation, optimisation and in vitro characterisation of PHBV and PLGA blend nanoparticles (NPs) for prolonged delivery of Teriparatide. Double emulsion solvent evaporation technique was employed for the fabrication of NPs. The nanoformulation was optimised using the Box-Behnken methodology. The morphological properties of NPs were assessed by both SEM and transmission electron microscopy (TEM). Encapsulation of Teriparatide within the NPs and lacking of chemical bonds between drug and copolymers were proved by XRPD, FTIR and DSC. The structural stability of Teriparatide after processing was confirmed by fluorescence spectrometry. The average size of optimised NPs was 250.0 nm with entrapment efficiency (EE) of 89.5% and drug loading (DL) of 5.0%. Teriparatide release from optimised NPs led to 64.4% release over 30 days and it showed a diffusion-based mechanism. Based on the favourable results, PHBV/PLGA blend NPs could be a promising candidate for designing a controlled release formulation of Teriparatide.
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http://dx.doi.org/10.1080/02652048.2016.1208296DOI Listing
August 2016

Nanoparticulate fingolimod delivery system based on biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV): design, optimization, characterization and in-vitro evaluation.

Pharm Dev Technol 2017 Nov 11;22(7):860-870. Epub 2015 Nov 11.

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

This study was focused on the fabrication, statistical optimization and in vitro characterization of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles loaded with fingolimod. PHBV-based fingolimod nanoparticles were prepared by single and double evaporation methods; the incorporation efficiency of fingolimod was higher with the single emulsion evaporation method in the nanosize range particles. Fingolimod HCL was neutralized with NaOH in order to slow down the release of the highly soluble fingolimod. The encapsulation efficiency of neutralized fingolimod was much higher (53-73%) due to the insoluble form of the drug used in encapsulation. It was found that the amount of fingolimod, concentration of PHBV and polyvinyl alcohol (PVA) would influence the encapsulation efficiency significantly. The effect of these parameters on the Particle size, PdI, loading capacity and loading efficacy was studied. The optimum conditions were 1.32% PHBV, 0.42% PVA and 5 mg fingolimod. The average size of optimized nanoparticles which measured with the aid of the Box-Behnken experimental design was 250 nm and entrapment efficiency of 73(%). Drug-release from the nanospheres over a four-week period has shown a characteristic triphasic release pattern with an initial burst effect.
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http://dx.doi.org/10.3109/10837450.2015.1108982DOI Listing
November 2017
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