Exploring Advantages/Disadvantages and Improvements in Overcoming Gene Delivery Barriers of Amino Acid Modified Trimethylated Chitosan

Zheng, Hao; Tang, Cui; Chen, Yin

doi:10.1007/s11095-014-1597-7

Cited by 15 publications

(10 citation statements)

References 40 publications

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“…The comparatively lower transfection efficiency of the polyplexes may be due to a high stability of condensed pDNA, leading to an incomplete release of pDNA inside the cytoplasmic compartment [48,49]. Further improvement of the transfection efficiency would presumably be achievable by addition of endosomal escape moieties [50,51], or with chitosan derivatives (e.g., trimethylation or amino acid conjugation) [52,53]. However, such efficacy improvements often impact the biocompatibility.…”

Section: Resultsmentioning

confidence: 99%

Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery

Yasar

Rossi

et al. 2018

Polymers

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Abstract:Despite the enormous potential of nanomedicine, the search for materials from renewable resources that balance bio-medical requirements and engineering aspects is still challenging. This study proposes an easy method to make nanoparticles composed of oxidized starch and chitosan, both isolated from natural biopolymers. The careful adjustment of C/N ratio, polymer concentration and molecular weight allowed for tuning of particle characteristics. The system's carrier capability was assessed both for anti-infectives and for nucleic acid. Higher starch content polyplexes were found to be suitable for high encapsulation efficiency of cationic anti-infectives and preserving their bactericidal function. A cationic carrier was obtained by coating the anionic polyplex with chitosan. Coating allowed for a minimal amount of cationic polymer to be employed and facilitated plasmid DNA loading both within the particle core and on the surface. Transfection studies showed encouraging result, approximately 5% of A549 cells with reporter gene expression. In summary, starch-chitosan complexes are suitable carriers with promising perspectives for pharmaceutical use.

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Section: Resultsmentioning

confidence: 99%

Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery

Yasar

Rossi

et al. 2018

Polymers

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“…A chitosan carrier in which only polyarginine was conjugated to its surface would have been a helpful control (R 6 -CS) in judging the efficacy of the histidine component of R 6 -H 6 CS in vitro and in vivo [ 60 ]. In another study, when multiple sites of chitosan were modified with only histidines, transfections in vitro and in vivo were only modestly increased [ 61 ]. The increased charge and buffering capacity with the addition of arginine and histidine copolymers were likely necessary to increase the transfection efficacy of chitosan.…”

Section: Beyond H-k Peptides and Polymersmentioning

confidence: 99%

The Multifaceted Histidine-Based Carriers for Nucleic Acid Delivery: Advances and Challenges

Mixson

2020

Pharmaceutics

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Histidines incorporated into carriers of nucleic acids may enhance the extracellular stability of the nanoparticle, yet aid in the intracellular disruption of the nanoparticle, enabling the release of the nucleic acid. Moreover, protonation of histidines in the endosomes may result in endosomal swelling with subsequent lysis. These properties of histidine are based on its five-member imidazole ring in which the two nitrogen atoms may form hydrogen bonds or act as a base in acidic environments. A wide variety of carriers have integrated histidines or histidine-rich domains, which include peptides, polyethylenimine, polysaccharides, platform delivery systems, viral phages, mesoporous silica particles, and liposomes. Histidine-rich carriers have played key roles in our understanding of the stability of nanocarriers and the escape of the nucleic acids from endosomes. These carriers show great promise and offer marked potential in delivering plasmids, siRNA, and mRNA to their intracellular targets.

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“…Trimethyl chitosan (TMC) is one of the intensively studied quarternized derivatives of chitosan in gene delivery applications [45,46,47,48,49]. One of the important advantages of trimethylation is that chitosan’s solubility can be increased in physiological pH.…”

Section: Chitosan As Gene Delivery Vehicle For Cancer Therapymentioning

confidence: 99%

“…The drug carrying ability of TMC nanoparticles has also been harnessed in drug gene co-delivery towards cancer cells. In a recent study, the triple negative MDA-MB-231 (human breast adenocarcinoma) cell line was successfully transfected by high mobility group protein 2 (HMGA-2) siRNA with simultaneous delivery of chemotherapeutic doxorubicin using a TMC nanoparticle system [49]. The anti-cancer effect of doxorubicin has been enhanced by conjunctional delivery of siRNA that silenced HMGA-2 gene expression.…”

Section: Chitosan As Gene Delivery Vehicle For Cancer Therapymentioning

confidence: 99%

Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

2017

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Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.

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Exploring Advantages/Disadvantages and Improvements in Overcoming Gene Delivery Barriers of Amino Acid Modified Trimethylated Chitosan

Abstract: Coordination of multiple contributing effects to conquer all delivery obstacles was necessitated for improved transfection efficiency, which would provide insights into rational design of gene delivery vehicles.

Cited by 15 publications

References 40 publications

Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery

Starch-Chitosan Polyplexes: A Versatile Carrier System for Anti-Infectives and Gene Delivery

The Multifaceted Histidine-Based Carriers for Nucleic Acid Delivery: Advances and Challenges

Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

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