論文

査読有り 国際誌
2020年6月15日

Developing spray-freeze-dried particles containing a hyaluronic acid-coated liposome-protamine-DNA complex for pulmonary inhalation.

International journal of pharmaceutics
  • Kaori Fukushige
  • ,
  • Tatsuaki Tagami
  • ,
  • Munekazu Naito
  • ,
  • Eiichi Goto
  • ,
  • Shuichi Hirai
  • ,
  • Naoyuki Hatayama
  • ,
  • Hiroki Yokota
  • ,
  • Takao Yasui
  • ,
  • Yoshinobu Baba
  • ,
  • Tetsuya Ozeki

583
開始ページ
119338
終了ページ
119338
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ijpharm.2020.119338

The liposome-protamine-DNA complex (LPD) is an effective cationic carrier of various nucleic acid constructs such as plasmid DNA and small interfering RNA (siRNA). Hyaluronic acid coated on LPD (LPDH) reduces cytotoxicity and maintains the silencing effect of LPD-encapsulated siRNA. Herein, we aim to develop LPD- or LPDH-containing spray-freeze-dried particles (SFDPs) for therapeutic delivery of siRNA to the lungs. LPD- or LPDH-containing SFDPs (LPD- or LPDH-SFDPs) were synthesized and their structure and function as gene carriers were evaluated using physical and biological methods. The particle size of LPDH, but not of LPD, was constant after re-dispersal from the SFDPs and the amount of siRNA encapsulated in LPDH was larger than that in LPD after re-dispersal from the SFDPs. The in vitro pulmonary inhalation properties of LPDH-SFDPs and LPD-SFDPs were almost the same. The cytotoxicity of LPDH-SFDPs in human umbilical vein endothelial cells (HUVEC) was greatly decreased compared with that of LPD-SFDPs. In addition, Bcl-2 siRNA in LPDH-SFDPs had a significant gene silencing effect in human lung cancer cells (A549), whereas Bcl-2 siRNA in LPD-SFDPs had little effect. These results indicate that compared with LPD, LPDH is more useful for developing SFDPs for siRNA pulmonary inhalation.

リンク情報
DOI
https://doi.org/10.1016/j.ijpharm.2020.119338
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32311468

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