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Article ; Online: Knowledge Gaps in Generating Cell-Based Drug Delivery Systems and a Possible Meeting with Artificial Intelligence.

Mozafari, Negin / Mozafari, Niloofar / Dehshahri, Ali / Azadi, Amir

2023 Volume 20, Issue 8, Page(s) 3757–3778

Abstract: Cell-based drug delivery systems are new strategies in targeted delivery in which cells or cell-membrane-derived systems are used as carriers and release their cargo in a controlled manner. Recently, great attention has been directed to cells as carrier ... ...

Abstract	Cell-based drug delivery systems are new strategies in targeted delivery in which cells or cell-membrane-derived systems are used as carriers and release their cargo in a controlled manner. Recently, great attention has been directed to cells as carrier systems for treating several diseases. There are various challenges in the development of cell-based drug delivery systems. The prediction of the properties of these platforms is a prerequisite step in their development to reduce undesirable effects. Integrating nanotechnology and artificial intelligence leads to more innovative technologies. Artificial intelligence quickly mines data and makes decisions more quickly and accurately. Machine learning as a subset of the broader artificial intelligence has been used in nanomedicine to design safer nanomaterials. Here, how challenges of developing cell-based drug delivery systems can be solved with potential predictive models of artificial intelligence and machine learning is portrayed. The most famous cell-based drug delivery systems and their challenges are described. Last but not least, artificial intelligence and most of its types used in nanomedicine are highlighted. The present Review has shown the challenges of developing cells or their derivatives as carriers and how they can be used with potential predictive models of artificial intelligence and machine learning.
MeSH term(s)	Artificial Intelligence ; Machine Learning ; Nanotechnology ; Nanomedicine ; Drug Delivery Systems
Language	English
Publishing date	2023-07-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/acs.molpharmaceut.3c00162
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Article: Preparation and characterization of a nanohydroxyapatite and sodium fluoride loaded chitosan-based

Rafiee, Azade / Mozafari, Negin / Fekri, Neda / Memarpour, Mahtab / Azadi, Amir

Heliyon

2024 Volume 10, Issue 2, Page(s) e24217

Abstract: The development of remineralizing smart biomaterials is a contemporary approach to caries prevention. The present study aimed at formulation preparation and characterization of a thermoresponsive oral gel based on poloxamer and chitosan loaded with ... ...

Abstract	The development of remineralizing smart biomaterials is a contemporary approach to caries prevention. The present study aimed at formulation preparation and characterization of a thermoresponsive oral gel based on poloxamer and chitosan loaded with sodium fluoride (NaF) and nanohydroxyapatite (nHA) to treat demineralization. The chemical structure and morphology of the formulation were characterized using FTIR and FESEM-EDS tests. Hydrogel texture, rheology, and stability were also examined. The hydrogel was in a sol state at room temperature and became gel after being placed at 37 °C with no significance different in gelation time with the formulation without nHA and NaF as observed by
Language	English
Publishing date	2024-01-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2024.e24217
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Article ; Online: Preparation and characterization of a nanohydroxyapatite and sodium fluoride loaded chitosan-based in situ forming gel for enamel biomineralization

Azade Rafiee / Negin Mozafari / Neda Fekri / Mahtab Memarpour / Amir Azadi

Heliyon, Vol 10, Iss 2, Pp e24217- (2024)

2024

Abstract	The development of remineralizing smart biomaterials is a contemporary approach to caries prevention. The present study aimed at formulation preparation and characterization of a thermoresponsive oral gel based on poloxamer and chitosan loaded with sodium fluoride (NaF) and nanohydroxyapatite (nHA) to treat demineralization. The chemical structure and morphology of the formulation were characterized using FTIR and FESEM-EDS tests. Hydrogel texture, rheology, and stability were also examined. The hydrogel was in a sol state at room temperature and became gel after being placed at 37 °C with no significance different in gelation time with the formulation without nHA and NaF as observed by t-test. The FTIR spectrum of nHA/NaF/chitosan-based hydrogel indicated the formation of physical crosslinking without any chemical interactions between the hydrogel components. The FESEM-EDS results demonstrated the uniform distribution of each element within the hydrogel matrix, confirming the successful incorporation of nHA and NaF in the prepared gel. The hardness, hydrogel’s adhesiveness, and cohesiveness were 0.9 mJ, 1.7 mJ, and 0.37, respectively, indicating gel stability and the acceptable retention time of hydrogels. The formulation exhibited a non-Newtonian shear-thinning pseudoplastic and thixotropic behavior with absolute physical stability. Within the limitation of in vitro studies, nHA/NaF/chitosan-based in situ forming gel demonstrated favorable properties, which could be trasnsorm into a gel state in oral cavity due to poloxamer and chitosan and can prevent dental caries due to nHA and NaF. We propose this formulation as a promising dental material in tooth surface remineralization.
Keywords	Dentistry ; Biomimetic ; Fluoride ; Hydroxyapatites ; In situ hydrogel ; Poloxamer ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	540 ; 620
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Recent Biomaterial-Assisted Approaches for Immunotherapeutic Inhibition of Cancer Recurrence.

Mozafari, Negin / Jahanbekam, Sheida / Ashrafi, Hajar / Shahbazi, Mohammad-Ali / Azadi, Amir

ACS biomaterials science & engineering

2024 Volume 10, Issue 3, Page(s) 1207–1234

Abstract: Biomaterials possess distinctive properties, notably their ability to encapsulate active biological products while providing biocompatible support. The immune system plays a vital role in preventing cancer recurrence, and there is considerable demand for ...

Abstract	Biomaterials possess distinctive properties, notably their ability to encapsulate active biological products while providing biocompatible support. The immune system plays a vital role in preventing cancer recurrence, and there is considerable demand for an effective strategy to prevent cancer recurrence, necessitating effective strategies to address this concern. This review elucidates crucial cellular signaling pathways in cancer recurrence. Furthermore, it underscores the potential of biomaterial-based tools in averting or inhibiting cancer recurrence by modulating the immune system. Diverse biomaterials, including hydrogels, particles, films, microneedles, etc., exhibit promising capabilities in mitigating cancer recurrence. These materials are compelling candidates for cancer immunotherapy, offering in situ immunostimulatory activity through transdermal, implantable, and injectable devices. They function by reshaping the tumor microenvironment and impeding tumor growth by reducing immunosuppression. Biomaterials facilitate alterations in biodistribution, release kinetics, and colocalization of immunostimulatory agents, enhancing the safety and efficacy of therapy. Additionally, how the method addresses the limitations of other therapeutic approaches is discussed.
MeSH term(s)	Humans ; Biocompatible Materials/therapeutic use ; Tissue Distribution ; Drug Delivery Systems ; Immunotherapy ; Neoplasms/drug therapy ; Tumor Microenvironment
Chemical Substances	Biocompatible Materials
Language	English
Publishing date	2024-02-28
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2373-9878
ISSN (online)	2373-9878
DOI	10.1021/acsbiomaterials.3c01347
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Article ; Online: Efficacy of Transcranial Direct Current Stimulation in Reducing Symptoms in Patients with Major Depressive Disorder

Parvin Rahmatinejad / Negin Past / Mohammadreza Mozafari / Fatemeh Shahi Sadrabadi

Majallah-i Dānishgāh-i ’Ulūm-i Pizishkī-i Shahīd Ṣadūqī Yazd, Vol 31, Iss 1, Pp 6327-

A Randomized Controlled Trial

2023 Volume 6338

Abstract: Introduction: In the recent years, transcranial direct current stimulation (tDCS) has been considered by researchers as one of the possible effective approach in the treatment of major depressive disorder. However, the results of these investigations are ...

Abstract	Introduction: In the recent years, transcranial direct current stimulation (tDCS) has been considered by researchers as one of the possible effective approach in the treatment of major depressive disorder. However, the results of these investigations are often contradictory. According to this, the purpose of this study was to determine the effectiveness of tDCS in reducing symptoms of people with major depressive disorder. Methods: In the sham-controlled randomized trial, twenty people with major depressive disorder referred to a private psychiatric clinic in Tehran City, Iran. They were selected by convenience sampling and divided into the intervention and control groups by randomized block design. tDCS was administered 2 mA, 20 minutes per session, for 10 sessions, 3 days per week. Immediately after, and one month after the intervention, the scores of the two groups were assessed in the Hamilton Depression Rating Scale and Beck Depression Inventory. The data were analyzed using SPSS version 16 software and using statistical methods of repeated analysis of variance and independent and dependent t-test. Results: The results of repeated analysis of variance for Hamilton (F = 43.5 and P = 0.017) and Beck (F = 125.12 and P = 0.022) depression scores showed the significance of the interaction effect of time (four stages of measurement) and group membership (experiment and control) (P < 0.05). In depression scores in both Hamilton and Beck scales in the experimental group in the intervention stages (Hamilton scale, P = 0.019, Beck scale = P = 0.017) and follow-up (Hamilton scale, P = 0.01, Beck scale = P = 0.03) was significantly reduced compared to the control group. Conclusion: The results of this study confirmed the effectiveness of tDCS in reducing symptoms of major depressive disorder. More clinical trials are needed to prove the effectiveness of tDCS compared to a variety of treatments
Keywords	efficacy ; transcranial direct current stimulation of the brain ; major depressive disorder ; sham-controlled randomized trial ; Medicine (General) ; R5-920
Subject code	150
Language	Persian
Publishing date	2023-04-01T00:00:00Z
Publisher	Shahid Sadoughi University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Metformin-loaded nanoerythrosomes: An erythrocyte-based drug delivery system as a therapeutic tool for glioma.

Moezzi, Seyed Mohammad Iman / Javadi, Parisa / Mozafari, Negin / Ashrafi, Hajar / Azadi, Amir

Heliyon

2023 Volume 9, Issue 6, Page(s) e17082

Abstract: Glioma is an intra-cranial malignancy with the origin of neural stem cells or precursor cells, the most prevalent brain tumor worldwide. Glioblastoma, the fourth-grade glioma, is a common brain tumor whose incidence rate is 5-7 people per 100,000 ... ...

Abstract	Glioma is an intra-cranial malignancy with the origin of neural stem cells or precursor cells, the most prevalent brain tumor worldwide. Glioblastoma, the fourth-grade glioma, is a common brain tumor whose incidence rate is 5-7 people per 100,000 populations annually. Despite their high mortality rate, all efforts for treatment have yet to achieve any desirable clinical outcome. The Wnt signaling pathway is a conserved pathway among species that seems to be a candidate for cancer therapy by its inhibition. Metformin is a known inhibitor of the Wnt signaling pathway. Its effects on glioma treatment have been observed in cellular, animal, and clinical experiments. Nanoerythrosomes are drug carriers obtained from the cellular membrane of red blood cells in nano size which can offer several characteristics to deliver metformin to brain tumors. They are good at loading and carrying hydrophilic drugs, they can protect metformin from its metabolizing enzymes, which are present in the blood-brain barrier, and they can extend the period of metformin presence in circulation. In this study, nanoerythrosomes were prepared by using the hypotonic buffer. They had particle sizes in the range of 97.1 ± 34.2 nm, and their loading efficiency and loading capacity were 72.6% and 1.66%, respectively. Nanoerythrosomes could reserve metformin in their structure for a long time, and only 50% of metformin was released after 30 h. Moreover, they released metformin at a low and approximately constant rate. Besides, nanoerythrosomes could tolerate various kinds of stress and maintain most of the drug in their structure. Altogether, nanoerythrosome can be a suitable drug delivery system to deliver therapeutic amounts of metformin to various tissues.
Language	English
Publishing date	2023-06-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2835763-2
ISSN	2405-8440
ISSN	2405-8440
DOI	10.1016/j.heliyon.2023.e17082
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Article ; Online: Assessing Oligonucleotide Binding to Double-Stranded DNA.

Mozafari, Negin / Umek, Tea

Methods in molecular biology (Clifton, N.J.)

2019 Volume 2036, Page(s) 91–112

Abstract: Sequence-specific targeting of double-stranded DNA (dsDNA) using synthetic oligonucleotides (ONs) has been under investigation in different therapeutic approaches. Several methods can be used to evaluate ONs effect and binding capacity to their target ... ...

Abstract	Sequence-specific targeting of double-stranded DNA (dsDNA) using synthetic oligonucleotides (ONs) has been under investigation in different therapeutic approaches. Several methods can be used to evaluate ONs effect and binding capacity to their target sequence. Here we describe some of the methods, which have been frequently used for assessing ONs binding to dsDNA.
MeSH term(s)	Base Pairing ; DNA/chemistry ; DNA/genetics ; DNA/metabolism ; DNA Cleavage ; Gene Expression Regulation ; Oligonucleotides/chemistry ; Oligonucleotides/genetics ; Oligonucleotides/metabolism
Chemical Substances	Oligonucleotides ; triplex DNA ; DNA (9007-49-2)
Language	English
Publishing date	2019-08-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9670-4_5
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Article ; Online: Metformin-loaded nanoerythrosomes

Seyed Mohammad Iman Moezzi / Parisa Javadi / Negin Mozafari / Hajar Ashrafi / Amir Azadi

Heliyon, Vol 9, Iss 6, Pp e17082- (2023)

An erythrocyte-based drug delivery system as a therapeutic tool for glioma

2023

Abstract	Glioma is an intra-cranial malignancy with the origin of neural stem cells or precursor cells, the most prevalent brain tumor worldwide. Glioblastoma, the fourth-grade glioma, is a common brain tumor whose incidence rate is 5–7 people per 100,000 populations annually. Despite their high mortality rate, all efforts for treatment have yet to achieve any desirable clinical outcome. The Wnt signaling pathway is a conserved pathway among species that seems to be a candidate for cancer therapy by its inhibition. Metformin is a known inhibitor of the Wnt signaling pathway. Its effects on glioma treatment have been observed in cellular, animal, and clinical experiments. Nanoerythrosomes are drug carriers obtained from the cellular membrane of red blood cells in nano size which can offer several characteristics to deliver metformin to brain tumors. They are good at loading and carrying hydrophilic drugs, they can protect metformin from its metabolizing enzymes, which are present in the blood-brain barrier, and they can extend the period of metformin presence in circulation. In this study, nanoerythrosomes were prepared by using the hypotonic buffer. They had particle sizes in the range of 97.1 ± 34.2 nm, and their loading efficiency and loading capacity were 72.6% and 1.66%, respectively. Nanoerythrosomes could reserve metformin in their structure for a long time, and only 50% of metformin was released after 30 h. Moreover, they released metformin at a low and approximately constant rate. Besides, nanoerythrosomes could tolerate various kinds of stress and maintain most of the drug in their structure. Altogether, nanoerythrosome can be a suitable drug delivery system to deliver therapeutic amounts of metformin to various tissues.
Keywords	Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	610
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Large-scale expansions of Friedreich's ataxia GAA•TTC repeats in an experimental human system: role of DNA replication and prevention by LNA-DNA oligonucleotides and PNA oligomers.

Rastokina, Anastasia / Cebrián, Jorge / Mozafari, Negin / Mandel, Nicholas H / Smith, C I Edvard / Lopes, Massimo / Zain, Rula / Mirkin, Sergei M

Nucleic acids research

2023 Volume 51, Issue 16, Page(s) 8532–8549

Abstract: Friedreich's ataxia (FRDA) is caused by expansions of GAA•TTC repeats in the first intron of the human FXN gene that occur during both intergenerational transmissions and in somatic cells. Here we describe an experimental system to analyze large-scale ... ...

Abstract	Friedreich's ataxia (FRDA) is caused by expansions of GAA•TTC repeats in the first intron of the human FXN gene that occur during both intergenerational transmissions and in somatic cells. Here we describe an experimental system to analyze large-scale repeat expansions in cultured human cells. It employs a shuttle plasmid that can replicate from the SV40 origin in human cells or be stably maintained in S. cerevisiae utilizing ARS4-CEN6. It also contains a selectable cassette allowing us to detect repeat expansions that accumulated in human cells upon plasmid transformation into yeast. We indeed observed massive expansions of GAA•TTC repeats, making it the first genetically tractable experimental system to study large-scale repeat expansions in human cells. Further, GAA•TTC repeats stall replication fork progression, while the frequency of repeat expansions appears to depend on proteins implicated in replication fork stalling, reversal, and restart. Locked nucleic acid (LNA)-DNA mixmer oligonucleotides and peptide nucleic acid (PNA) oligomers, which interfere with triplex formation at GAA•TTC repeats in vitro, prevented the expansion of these repeats in human cells. We hypothesize, therefore, that triplex formation by GAA•TTC repeats stall replication fork progression, ultimately leading to repeat expansions during replication fork restart.
MeSH term(s)	Humans ; DNA ; DNA Replication/drug effects ; Friedreich Ataxia/genetics ; Iron-Binding Proteins/genetics ; Oligonucleotides/pharmacology ; Peptide Nucleic Acids/pharmacology ; Saccharomyces cerevisiae/genetics ; Trinucleotide Repeat Expansion
Chemical Substances	DNA (9007-49-2) ; Iron-Binding Proteins ; locked nucleic acid ; Oligonucleotides ; Peptide Nucleic Acids
Language	English
Publishing date	2023-05-22
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	186809-3
ISSN	1362-4962 ; 1362-4954 ; 0301-5610 ; 0305-1048
ISSN (online)	1362-4962 ; 1362-4954
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkad441
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Article ; Online: Ultrasound-responsive hyaluronic acid hydrogel of hydrocortisone to treat osteoarthritis.

Jahanbekam, Sheida / Mozafari, Negin / Bagheri-Alamooti, Azar / Mohammadi-Samani, Soliman / Daneshamouz, Saeid / Heidari, Reza / Azarpira, Negar / Ashrafi, Hajar / Azadi, Amir

International journal of biological macromolecules

2023 Volume 240, Page(s) 124449

Abstract: One of the practical ways to manage the disease flares of arthritis is using an intra-articular depot formulation of glucocorticoids. Hydrogels, as controllable drug delivery systems, are hydrophilic polymers with distinctive properties, such as ... ...

Abstract	One of the practical ways to manage the disease flares of arthritis is using an intra-articular depot formulation of glucocorticoids. Hydrogels, as controllable drug delivery systems, are hydrophilic polymers with distinctive properties, such as remarkable water capacity and biocompatibility. This study aimed to design an injectable thermo-ultrasound-triggered drug carrier based on Pluronic® F-127, hyaluronic acid, and gelatin. The in situ hydrogel loaded by hydrocortison was developed and D-optimal design was used to formulate the process. The optimized hydrogel was combined with four different surfactants to better regulate the release rate. In situ gels composed of the hydrocortisone-loaded hydrogel and hydrocortisone-loaded mixed-micelle hydrogel were characterized. The hydrocortisone-loaded hydrogel and selected hydrocortisone-loaded mixed-micelle hydrogel showed a spherical shape and were nano-sized with a unique thermo-responsive nature able to prolong drug release. The ultrasound-triggered release study showed that drug release was time-dependent. By inducing osteoarthritis in a rat model, behavioral tests and histopathological analyses were carried out on the hydrocortisone-loaded hydrogel and a particular hydrocortisone-loaded mixed-micelle hydrogel. In vivo results showed that the selected hydrocortisone-loaded mixed-micelle hydrogel improved the status of the disease. Results highlighted the potential of ultrasound-responsive in situ-forming hydrogels as hopeful formulas for efficient treatment of arthritis.
MeSH term(s)	Animals ; Rats ; Hydrocortisone/pharmacology ; Hydrogels/pharmacology ; Hyaluronic Acid/pharmacology ; Micelles ; Osteoarthritis/drug therapy
Chemical Substances	Hydrocortisone (WI4X0X7BPJ) ; Hydrogels ; Hyaluronic Acid (9004-61-9) ; Micelles
Language	English
Publishing date	2023-04-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2023.124449
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