Intranasal gene therapy for the treatment of neurological disorders

Dhas, Namdev; Mehta, Tejal; Sharma, Shilpa; Garkal, Atul; Yadav, Dattatray; Hariharan, Kartik; Shamjetshabam, Babeeta; Khot, Shubham; Kudarha, Ritu; Bangar, Priyanka; Arbade, Gajanan Kashinathrao; Kalyankar, Pratap

doi:10.1016/b978-0-12-822522-6.00017-5

Cited by 4 publications

(2 citation statements)

References 191 publications

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“…Among polymers, polyaziridines (PA) have frequently been employed for gene therapy (Dhas et al, 2021;Wang et al, 2020). Linear PA have protonable nitrogen at every third atom of the polymer backbone (Sun, Tang, Uludaǧ, & Cuervo, 2011).…”

Section: Introductionmentioning

confidence: 99%

DNA Release from Polyaziridine Polyplexes Aided by Biomacromolecules: Effect of pH

Bibi,

Shah

2023

Acta Sci Technol

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The pH dependence of heparin and dextran sulfate aided release of DNA from its polyplexes with polyaziridine (PA) has been investigated using Quartz crystal microbalance with dissipation monitoring (QCM-D). The acoustic behavior of ternary systems indicated that the DNA decondensation was favored at physiological pH. When pH < 7.4, PA was significantly positively charged and ternary complexation occurred. When pH exceeded 7.4, very small proportion of DNA was released upon heparin addition due to marked reduction in cationic nature of PA. An increase in thickness at the interface due to adsorbed material at pH 9.0 showed the retention of heparin on the surface despite of negligible release of DNA. In terms of PA binding, heparin proved to be a better competitor than dextran sulfate.

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Section: Introductionmentioning

confidence: 99%

DNA Release from Polyaziridine Polyplexes Aided by Biomacromolecules: Effect of pH

Bibi,

Shah

2023

Acta Sci Technol

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“…The chances of variable dosing may arise due to improper administration. The inter-individual differences in physiology and pathologies like cold and congestion can also introduce variability in absorption profiles ( Podolska et al, 2012 ; Kanazawa, 2015 ; Dhas. et al, 2021 ; Hammond et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Intranasal delivery: An attractive route for the administration of nucleic acid based therapeutics for CNS disorders

Shah

Lalan²,

Barve

2022

Front. Pharmacol.

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The etiologies of several cardiovascular, inflammatory, neurological, hereditary disorders, cancer, and infectious diseases have implicated changes in the genetic set up or genetic mutations as the root cause. Nucleic acid based therapeutics (NBTs) is a new class of biologics that are known to regulate gene expression at the transcriptional and post-transcriptional level. The NBTs include oligonucleotides, nucleosides, antisense RNA, small interfering RNAs, micro RNA etc. In recent times, this new category of biologics has found enormous potential in the management of cardiovascular, inflammatory, neurological disorders, cancer, infectious diseases and organ transplantation. However, the delivery of NBTs is highly challenging in terms of target specificity (intracellular delivery), mononuclear phagocyte system uptake, stability and biodistribution. Additionally, management of the above mentioned disorders require regular and intrusive therapy making non-invasive routes preferable in comparison to invasive routes like parenteral. The nasal route is garnering focus in delivery of NBTs to the brain in the management of several CNS disorders due to the associated merits such as non-invasiveness, possibility of chronic delivery, improved patient compliance, avoidance of hepatic and gastrointestinal metabolism as well as ability to bypass the BBB. Hence in recent times, this route has been sought by the reserachers as an alternative to parenteral therapy for the delivery of several NBTs. This review shall focus on an array of NBTs delivered through nasal route, their challenges, applications and opportunities. The novel delivery systems for incorporating NBTs; their targeting strategies shall be critically reviewed. The challenges towards regulatory approvals and commercialization shall also be discussed at large. Comparison of learnings derived from the success and barriers in nasal delivery of NBTs will help in identification of futuristic opportunities for their translation from bench to bedside.

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