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  1. Article: A combinatorial study of experimental analysis and mathematical modeling: How do chitosan nanoparticles deliver therapeutics into cells?

    Dey, Anomitra / Dandekar, Prajakta / Jain, Ratnesh / Stenberg, Jonas

    Carbohydrate polymers. 2020 Feb. 01, v. 229

    2020  

    Abstract: Chitosan nanosystems have been widely explored to deliver therapeutic into cells. The cationic nature of the polymer facilitates its entry into the cell via the negatively charged lipid bilayer. Though the interaction is feasible for successful payload ... ...

    Abstract Chitosan nanosystems have been widely explored to deliver therapeutic into cells. The cationic nature of the polymer facilitates its entry into the cell via the negatively charged lipid bilayer. Though the interaction is feasible for successful payload delivery, very little is known about the mechanistic aspects and kinetics of interaction of chitosan nanoparticles (Chnps) with the cellular bilayer membrane. Moreover, the precise mechanism of delivery of therapeutic agents by the Chnps is unknown. The polymerbilayer membrane is anticipated to play a crucial role in deciding its ultimate intracellular fate, while delivering its therapeutic payload. Here, we have made an attempt to understand the interaction of Chnps with the cellular membrane for delivering payload, through experimental analysis and predictive mathematical modeling. We observed that the positively charged, mucoadhesive Chnps lack specificity towards a particular cell type, but are rather successful in the intracellular delivery of nucleic acids.
    Keywords bioadhesives ; chitosan ; lipid bilayers ; mathematical models ; nanoparticles ; nucleic acids ; therapeutics
    Language English
    Dates of publication 2020-0201
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 1501516-6
    ISSN 1879-1344 ; 0144-8617
    ISSN (online) 1879-1344
    ISSN 0144-8617
    DOI 10.1016/j.carbpol.2019.115437
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: A combinatorial study of experimental analysis and mathematical modeling: How do chitosan nanoparticles deliver therapeutics into cells?

    Dey, Anomitra / Stenberg, Jonas / Dandekar, Prajakta / Jain, Ratnesh

    Carbohydrate polymers

    2019  Volume 229, Page(s) 115437

    Abstract: Chitosan nanosystems have been widely explored to deliver therapeutic into cells. The cationic nature of the polymer facilitates its entry into the cell via the negatively charged lipid bilayer. Though the interaction is feasible for successful payload ... ...

    Abstract Chitosan nanosystems have been widely explored to deliver therapeutic into cells. The cationic nature of the polymer facilitates its entry into the cell via the negatively charged lipid bilayer. Though the interaction is feasible for successful payload delivery, very little is known about the mechanistic aspects and kinetics of interaction of chitosan nanoparticles (Chnps) with the cellular bilayer membrane. Moreover, the precise mechanism of delivery of therapeutic agents by the Chnps is unknown. The polymerbilayer membrane is anticipated to play a crucial role in deciding its ultimate intracellular fate, while delivering its therapeutic payload. Here, we have made an attempt to understand the interaction of Chnps with the cellular membrane for delivering payload, through experimental analysis and predictive mathematical modeling. We observed that the positively charged, mucoadhesive Chnps lack specificity towards a particular cell type, but are rather successful in the intracellular delivery of nucleic acids.
    MeSH term(s) Cell Line, Tumor ; Cell Membrane/metabolism ; Chitosan/chemistry ; Chitosan/metabolism ; Drug Carriers/chemistry ; Drug Carriers/metabolism ; Endocytosis/physiology ; Fluorescein-5-isothiocyanate/chemistry ; Fluorescent Dyes/chemistry ; Humans ; Kinetics ; Lysosomes/metabolism ; Membrane Fluidity ; Models, Biological ; Nanoparticles/chemistry ; Nanoparticles/metabolism
    Chemical Substances Drug Carriers ; Fluorescent Dyes ; Chitosan (9012-76-4) ; Fluorescein-5-isothiocyanate (I223NX31W9)
    Language English
    Publishing date 2019-10-04
    Publishing country England
    Document type Journal Article
    ZDB-ID 1501516-6
    ISSN 1879-1344 ; 0144-8617
    ISSN (online) 1879-1344
    ISSN 0144-8617
    DOI 10.1016/j.carbpol.2019.115437
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mapping of Methyl Epitopes of a Peptide-Drug with Its Receptor by 2D STDD-Methyl TROSY NMR Spectroscopy.

    Dey, Anomitra / Mitra, Debarghya / Rachineni, Kavitha / Khatri, Lakshya Raj / Paithankar, Harshad / Vajpai, Navratna / Kumar, Ashutosh

    Chembiochem : a European journal of chemical biology

    2022  Volume 23, Issue 23, Page(s) e202200489

    Abstract: The current trend in the biopharmaceutical market has boosted the development and production of biological drugs with high efficacy and fidelity for receptor binding. While high-resolution structural insights into binding epitopes of the receptor are ... ...

    Abstract The current trend in the biopharmaceutical market has boosted the development and production of biological drugs with high efficacy and fidelity for receptor binding. While high-resolution structural insights into binding epitopes of the receptor are indispensable for better therapeutic design, it is tedious and costly. In this work, we develop a protocol by integrating two well-known NMR-based solution-state methods. Saturation transfer double-difference with methyl-TROSY (STDD-Methyl TROSY NMR) was used to probe methyl binding epitopes of the ligand in a label-free environment. This study was carried out with Human insulin as a model peptide drug, with the insulin growth factor receptor (IGFR), which is an off-target receptor for insulin. Methyl epitopes identified from STDD-Methyl TROSY NMR spectroscopy were validated through the HADDOCK platform to generate a drug-receptor model. Since this method can be applied at natural abundance, it has the potential to screen a large set of peptide-drug interactions for optimum receptor binding. Thus, we propose STDD-Methyl TROSY NMR spectroscopy as a technique for rapid screening of biologics for the development of optimized biopharmaceutics.
    MeSH term(s) Humans ; Epitopes ; Magnetic Resonance Spectroscopy/methods ; Ligands ; Peptides ; Insulins ; Nuclear Magnetic Resonance, Biomolecular/methods
    Chemical Substances Epitopes ; Ligands ; Peptides ; Insulins
    Language English
    Publishing date 2022-11-10
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2020469-3
    ISSN 1439-7633 ; 1439-4227
    ISSN (online) 1439-7633
    ISSN 1439-4227
    DOI 10.1002/cbic.202200489
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Role of proton balance in formation of self-assembled chitosan nanoparticles

    Dey, Anomitra / Aditya Kamat / Dganit Danino / Ellina Kesselman / Prajakta Dandekar / Ratnesh Jain / Sonal Nayak

    Colloids and surfaces. 2018 June 01, v. 166

    2018  

    Abstract: Researchers have explored the ability of chitosan to form nanoparticles, to suit varying applications, ranging from wound-healing to gene delivery. Ionic gelation is a widely used method for formulating chitosan nanoparticles, where self-assembly plays a ...

    Abstract Researchers have explored the ability of chitosan to form nanoparticles, to suit varying applications, ranging from wound-healing to gene delivery. Ionic gelation is a widely used method for formulating chitosan nanoparticles, where self-assembly plays a crucial role. This self-assembly is initially promoted by hydrophilic-hydrophobic parity amongst individual chitosan residues, along with electrostatic and Van der Waals interactions with the cross-linker. However, until now the intrinsic ability of chitosan to self-assemble is not widely studied; hence, we investigate the self-assembly of chitosan, based on proton balance between its protonated and deprotonated residues, to promote facile nanoparticle synthesis. This is one of the first reports that highlights subtle but critical influence of proton balance in the chitosan polymer on the formation of chitosan nanoparticles.
    Keywords chitosan ; colloids ; gelation ; gene transfer ; nanoparticles ; polymers ; van der Waals forces
    Language English
    Dates of publication 2018-0601
    Size p. 127-134.
    Publishing place Elsevier B.V.
    Document type Article
    ZDB-ID 1500523-9
    ISSN 1873-4367 ; 0927-7765
    ISSN (online) 1873-4367
    ISSN 0927-7765
    DOI 10.1016/j.colsurfb.2018.03.017
    Database NAL-Catalogue (AGRICOLA)

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  5. Article ; Online: Role of proton balance in formation of self-assembled chitosan nanoparticles.

    Dey, Anomitra / Kamat, Aditya / Nayak, Sonal / Danino, Dganit / Kesselman, Ellina / Dandekar, Prajakta / Jain, Ratnesh

    Colloids and surfaces. B, Biointerfaces

    2018  Volume 166, Page(s) 127–134

    Abstract: Researchers have explored the ability of chitosan to form nanoparticles, to suit varying applications, ranging from wound-healing to gene delivery. Ionic gelation is a widely used method for formulating chitosan nanoparticles, where self-assembly plays a ...

    Abstract Researchers have explored the ability of chitosan to form nanoparticles, to suit varying applications, ranging from wound-healing to gene delivery. Ionic gelation is a widely used method for formulating chitosan nanoparticles, where self-assembly plays a crucial role. This self-assembly is initially promoted by hydrophilic-hydrophobic parity amongst individual chitosan residues, along with electrostatic and Van der Waals interactions with the cross-linker. However, until now the intrinsic ability of chitosan to self-assemble is not widely studied; hence, we investigate the self-assembly of chitosan, based on proton balance between its protonated and deprotonated residues, to promote facile nanoparticle synthesis. This is one of the first reports that highlights subtle but critical influence of proton balance in the chitosan polymer on the formation of chitosan nanoparticles.
    MeSH term(s) Chitosan/chemistry ; Nanoparticles/chemistry ; Polymers/chemistry ; Protons
    Chemical Substances Polymers ; Protons ; Chitosan (9012-76-4)
    Language English
    Publishing date 2018-03-14
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1500523-9
    ISSN 1873-4367 ; 0927-7765
    ISSN (online) 1873-4367
    ISSN 0927-7765
    DOI 10.1016/j.colsurfb.2018.03.017
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Potential Gene Therapy Towards Treating Neurodegenerative Disea ses Employing Polymeric Nanosystems.

    Bangde, Prachi / Atale, Sonal / Dey, Anomitra / Pandit, Ashish / Dandekar, Prajakta / Jain, Ratnesh

    Current gene therapy

    2017  Volume 17, Issue 2, Page(s) 170–183

    Abstract: Background: Recent integrated approaches involving nanotechnology and gene therapy have accelerated development of efficient drug delivery to the central nervous system (CNS). Neurodegenerative disorders are closely associated with genetic inheritance ... ...

    Abstract Background: Recent integrated approaches involving nanotechnology and gene therapy have accelerated development of efficient drug delivery to the central nervous system (CNS). Neurodegenerative disorders are closely associated with genetic inheritance and mutation.
    Materials: Nanotechnology has allowed effective engineering of various such polymeric structures. Moreover, availability of a wide array of polymeric materials has enabled fabrication of biocompatible and biodegradable delivery vehicles. Our manuscript focuses on the ideal features and properties of polymeric nanoparticles that have enabled successful gene therapy for neurodegenerative disorders, as well as the challenges that are posing difficulties in their practical application. We have highlighted these aspects through examples of polymeric nanoparticles that have exhibited therapeutic promise in the treatment of neurological disorders and mutations.
    Methods: Complete cure of these diseases is a challenging task and gene therapy appears as a realistic approach for their treatment. Gene therapy allows effective replacement or suppression of faulty genes, thereby increasing chances for neuron survival and repair. However, successful delivery of naked genetic material to CNS faces severe obstacles due to possible degradation and restricted transportation of these biological entities across the blood brain barrier (BBB). Structurally, the BBB is composed of several tight junctions, making the membrane highly selective towards the entry of molecules.
    Conclusion: In order to target BBB for treating neurodegenerative diseases, it is essential to develop a tailor-made system that may not only cross this barrier, but also effectively modulate the expression of disease-causing genes. Stabilization of therapeutic genes and their effective, targeted delivery may be possible using polymeric nanoparticles as carriers.
    Language English
    Publishing date 2017
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2146187-9
    ISSN 1875-5631 ; 1566-5232
    ISSN (online) 1875-5631
    ISSN 1566-5232
    DOI 10.2174/1566523217666170510153845
    Database MEDical Literature Analysis and Retrieval System OnLINE

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