Histidine‐enhanced gene delivery systems: The state of the art

Hooshmand, Seyyed Emad; Sabet, Makkieh Jahanpeimay; Hasanzadeh, Akbar; Mousavi, Seyede Mahtab Kamrani; Moghadam, Niloofar Haeri; Hooshmand, Seyed Aghil; Rabiee, Navid; Liu, Yong; Hamblin, Michael R.; Karimi, Mahdi

doi:10.1002/jgm.3415

Cited by 17 publications

(19 citation statements)

References 212 publications

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“…Nonetheless, for instance histidine exhibits properties matching the required ones and accordingly yielded encouraging in vitro-and in vivoresults. [104,157] Once the requirements for a particular application have been established, it is therefore key to find nontoxic building blocks, meeting these requirements for the development of auxiliary agents that offer improved safety without sacrificing efficacy. To ensure this, a complete characterization of new excipients must include a comparison with the current lead compounds in terms of both efficacy and safety.…”

Section: Functional Propertiesmentioning

confidence: 99%

Biodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients

Jörgensen

Wibel

Bernkop‐Schnürch

2023

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The use of cationic and ionizable cationic lipids in pharmaceutical products, however, is a double-edged sword, as these excipients are of considerable safety concerns. Because of their permanent or pHdependent cationic nature, they perturbate cellular and nuclear membranes, trigger the release of degrading enzymes from lysosomes, cause mitochondrial permeabilization and dysfunction, generate reactive oxygen species (ROS), alter cytoplasmatic enzyme functions, and damage DNA. [3] To address this substantial shortcoming of cationic and ionizable cationic lipids, biodegradable alternatives have been introduced that are rapidly degraded in vivo to preferably endogenous metabolites. The design of such lipids is inspired by natural cationic or ionizable cationic compounds like arginine, lysine or betaine that are generally regarded as safe. Their conjugation to endogenous lipids like fatty acids or cholesterol results in amphiphilic lipids. As ester and amide bonds are cleaved in vivo by numerous enzymes such as lipases, esterases, and proteases, they are the preferred linkages between these natural building blocks.Since the FDA approved ethyl Nα-lauroyl-l-arginate as biodegradable food preservative being effective against a broad range of Gram-positive and Gram-negative bacteria, yeasts, and molds in 2005, [4] the potential use of biodegradable cationic and ionizable cationic lipids as pharmaceutical excipients has been evaluated by numerous research groups. As these excipients exhibit the same properties as their non-biodegradable counterparts but causing relatively low adverse effects, they will likely substitute currently used non-biodegradable lipids in the future. Within this review, we provide an overview on the different types of biodegradable cationic and ionizable cationic lipids, their synthesis and cleavage by endogenous enzymes. Applications in drug delivery systems and as antimicrobial agents are discussed. A guideline on their design and application is provided and an outlook on future developments is given. Building Blocks and Formation of Cationic and Ionizable Cationic LipidsGenerally, biodegradable cationic and ionizable cationic lipids are composed of biocompatible building blocks that are conjugated via a linkage such as an ester or amide bond. [5] Representative building blocks and linkages are depicted in Figure 1. Endogenous enzymes can break these linkages and degrade Cationic and ionizable cationic lipids are broadly applied as auxiliary agents, but their use is associated with adverse effects. If these excipients are rapidly degraded to endogenously occurring metabolites such as amino acids and fatty acids, their toxic potential can be minimized. So far, synthesized and evaluated biodegradable cationic and ionizable cationic lipids already showed promising results in terms of functionality and safety. Within this review, an overview about the different types of such biodegradable lipids, the available building blocks, their synthesis and cleavage by endogenous enzymes is provided. Moreover, ...

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Section: Functional Propertiesmentioning

confidence: 99%

Biodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients

Jörgensen

Wibel

Bernkop‐Schnürch

2023

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“…In addition, lower cytotoxicity was shown relative to polyethyleneimine 25 kDa (PEI 25 kDa) due to the introduction of histidine residues. [ 139 ] Another PAMAM G2‐HRChol system for delivery of plasmid DNA (pDNA) to HeLa cells was reported by Thuy et al. in 2022.…”

Section: Utilization Of Dendrimers In Cancermentioning

confidence: 99%

“…In addition, lower cytotoxicity was shown relative to polyethyleneimine 25 kDa (PEI 25 kDa) due to the introduction of histidine residues. [139] Another PAMAM G2-HRChol system for delivery of plasmid DNA (pDNA) to HeLa cells was reported by Thuy et al in 2022. [140] Dipeptide (histidine arginine) and cholesterol were conjugated on the surface of G2 PAMAM dendrimer in different ratios (6% or 23%).…”

Section: Dna Deliverymentioning

confidence: 99%

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

Zha

Liu

et al. 2022

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immune responses, activating cellular machinery causing cell stress, cytotoxicity, lack of selectivity, increasing the likelihood of replication competence, and the constrained structure of insert-size, which can limit their biological and medical applications. [2][3][4] By contrast, various forms of nonviral vectors are widely developed and applied in biomedical research because of their low immunogenicity, high biocompatibility, simplicity in structural pattern, ease of size adjustment, practicality in designing various active sites, and low cost of production. [5,6] The most widely studied nonviral vectors are liposomes, inorganic nanoparticles, polymers, and dendrimers. [7] Liposomes are small spherical vesicles from cholesterol and phospholipids characterized with the surface that can be modified using glycolipids or sialic acid. Yet, the unmodified forms of liposomes are structurally unstable and could easily be eliminated by means of body circulation. [8] In this situation, stable inorganic nanoparticles, such as calcium phosphate (Ca 3 (PO 4 ) 2 ), gold (Au), iron oxide (Fe 3 O 4 ), and lanthanide-based nanoparticles are widely used, mainly due to their good hydrophilicity and excellent biocompatibility. [9][10][11] Depending on their chemical core composition, these inorganic nanoparticles display different properties and efficiencies. Lately, inorganic nanoparticles have been developed as effective drug delivery systems and used in many diagnostic techniques. [12] In addition, polymers are widely used as nonviral vectors as well. [13][14][15] Polymers are biodegradable nanomaterials with stable and easily modifiable 3D structures. Their uncomplicated synthesis process allows for large-scale production and safe clinical use compared to inorganic nanoparticles. [16] Notably, dendrimers are hyperbranched polymers with a well-defined chemical structure: a core at the center occupied by array of convergent reactive chain-ends and surface that can easily be modified. [17] The chemistry of dendrimers was first described by Buhleier et al. in 1978. [18] In 1985, Tomalia et al. reported a newer kind of dendrimers based on the mixture of amines and amides, termed polyamidoamine (PAMAM) dendrimers. [19] Dendrimers are intermeshed synthetic organic macromolecules with 3D architecture composition and abundant terminal functional groups. They are well-defined monodispersity-sized materials with extraordinary membrane interaction properties Dendrimers are polymers with well-defined 3D branched structures that are vastly utilized in various neurotheranostics and biomedical applications, particularly as nanocarrier vectors. Imaging agents can be loaded into dendrimers to improve the accuracy of diagnostic imaging processes. Likewise, combining pharmaceutical agents and anticancer drugs with dendrimers can enhance their solubility, biocompatibility, and efficiency. Practically, by modifying ligands on the surface of dendrimers, effective therapeutic and diagnostic platforms can be constructed and implemented for target...

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“…The TBL section was designed according to the recommendation of Michaelsen and Sweet. 17 Considering the nature of clinical pharmacology and endodontics, 18,19 the size of the team was reduced to two students per group. The groups were mainly formed by the students themselves, but the gender, character and previous education were taken into account when composing the study teams.…”

Section: The Structure Of Tblmentioning

confidence: 99%

The introduction of team‐based learning into the clinical pharmacology section of the endodontics clinical course

Chen

Yue

Liu

et al. 2022

Clin Exp Pharma Physio

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Team-based learning (TBL) has been widely applied and evaluated to produce better student outcomes. TBL has been introduced into the clinical pharmacology section of the endodontics clinical course at the School of Stomatology, Wuhan University since 2021. Here, the teaching experience in this course was summarized. The TBL course consisted of a knowledge assignment, intrateam and interteam discussion, practicing, evaluation, cases discussion and examination. The topics of the TBL class included cavity preparation and filling for treatment of dental caries, disinfection, and shaping and filling of root canal for root canal therapy. A total of 64 students participated in the TBL course. The students completed course work and hands-on practice to the satisfaction of the instructor. Furthermore, most participants held positive attitudes toward the TBL course because TBL provided the opportunity for teamwork to enable them to acquire and understand the therapeutic drug and material more quickly and made them more confident in the following practice. Our experience suggested that the application of the TBL contributed to the authentic practice of the endodontics clinical course.

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Histidine‐enhanced gene delivery systems: The state of the art

Cited by 17 publications

References 212 publications

Biodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients

Biodegradable Cationic and Ionizable Cationic Lipids: A Roadmap for Safer Pharmaceutical Excipients

Polymeric Dendrimers as Nanocarrier Vectors for Neurotheranostics

The introduction of team‐based learning into the clinical pharmacology section of the endodontics clinical course

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