Branched polyethylenimine-grafted-carboxymethyl chitosan copolymer enhances the delivery of pDNA or siRNA in vitro and in vivo

Park, Seong-Cheol; Nam, Joung-Pyo; Kim, Young‐Min; Kim, Junho; Nah, Jae‐Woon; Jang, Mi-Kyeong

doi:10.2147/ijn.s50911

Cited by 18 publications

(8 citation statements)

References 33 publications

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“…The polyplexes were injected i.v. and mediated excellent GFP expression in the lung [88]. Thus, it is possible that this delivery system may as well be successful for siRNA delivery to the lung after i.v.…”

Section: Nanocarrier Chemistrymentioning

confidence: 99%

“…Since 2011, a total of ten publications have described nucleic acid delivery to the lung with unmodified PEI [108-110] or the development of copolymers that are expected to have better biocompatibility and targeting characteristics [88, 111-116]. PEI is often used in proof-of-principle studies or set-ups where a method is optimized.…”

Section: Nanocarrier Chemistrymentioning

confidence: 99%

“…Although the aim of this review is to discuss pulmonary delivery of siRNA, we did not want to disregard a variety of recent reports that target the lung, lung cancer or metastases via the systemic route [68-76, 88, 90, 107, 110, 113, 114, 125, 127, 129-132, 135, 147, 148]. Although i.v.…”

Section: Administration Routementioning

confidence: 99%

“…Since the establishment of tumor and metastasis models requires very sophisticated knowledge and handling, many studies performed simpler proof-of-principle experiments in which they knocked down the expression of the reporter genes (Enhanced) Green Fluorescent Protein ((e)GFP) [63, 69, 88, 108, 123] or Luciferase [31, 117]. These modes are especially helpful for in vitro studies in which the performance of a carrier is determined or optimized [117, 123], or for in vivo experiments that are interested in determining the biodistribution [31, 69, 88, 108, 148] or optimizing the formulation [148].…”

Section: Disease Modelsmentioning

confidence: 99%

“…These modes are especially helpful for in vitro studies in which the performance of a carrier is determined or optimized [117, 123], or for in vivo experiments that are interested in determining the biodistribution [31, 69, 88, 108, 148] or optimizing the formulation [148]. …”

Section: Disease Modelsmentioning

confidence: 99%

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siRNA Delivery to the lung: What's new?

Merkel

Rubinstein

Kissel

2014

Advanced Drug Delivery Reviews

115

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RNA interference (RNAi) has been thought of as the general answer to many unmet medical needs. After the first success stories, it soon became obvious that short interfering RNA (siRNA) is not suitable for systemic administration due to its poor pharmacokinetics. Therefore local administration routes have been adopted for more successful in vivo RNAi. This paper reviews nucleic acid modifications, nanocarrier chemistry, animal models used in successful pulmonary siRNA delivery, as well as clinical translation approaches. We summarize what has been published recently and conclude with the potential problems that may still hamper the efficient clinical application of RNAi in the lung.

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Section: Nanocarrier Chemistrymentioning

confidence: 99%

Section: Nanocarrier Chemistrymentioning

confidence: 99%

Section: Administration Routementioning

confidence: 99%

Section: Disease Modelsmentioning

confidence: 99%

Section: Disease Modelsmentioning

confidence: 99%

See 3 more Smart Citations

siRNA Delivery to the lung: What's new?

Merkel

Rubinstein

Kissel

2014

Advanced Drug Delivery Reviews

115

View full text Add to dashboard Cite

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Carboxymethyl chitosan prolongs adenovirus‐mediated expression of IL‐10 and ameliorates hepatic fibrosis in a mouse model

Gou

Weng

Chen

et al. 2022

Bioengineering & Transla Med

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Effective and safe liver‐directed gene therapy has great promise in treating a broad range of liver diseases. While adenoviral (Ad) vectors have been widely used for efficacious in vivo gene delivery, their translational utilities are severely limited due to the short duration of transgene expression and solicitation of host immune response. Used as a promising polymeric vehicle for drug release and nucleic acid delivery, carboxymethyl chitosan (CMC) is biocompatible, biodegradable, anti‐microbial, inexpensive, and easy accessible. Here, by exploiting its biocompatibility, controlled release capability and anti‐inflammatory activity, we investigated whether CMC can overcome the shortcomings of Ad‐mediated gene delivery, hence improving the prospect of Ad applications in gene therapy. We demonstrated that in the presence of optimal concentrations of CMC, Ad‐mediated transgene expression lasted up to 50 days after subcutaneous injection, and at least 7 days after intrahepatic injection. Histologic evaluation and immunohistochemical analysis revealed that CMC effectively alleviated Ad‐induced host immune response. In our proof‐of‐principle experiment using the CCl4‐induced experimental mouse model of chronic liver damage, we demonstrated that repeated intrahepatic administrations of Ad‐IL10 mixed with CMC effectively mitigated the development of hepatic fibrosis. Collectively, these results indicate that CMC can improve the prospect of Ad‐mediated gene therapy by diminishing the host immune response while allowing readministration and sustained transgene expression.

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