Related Experiment Video
Updated: Dec 23, 2025
Intratracheal Administration of Dry Powder Formulation in Mice
Published on: July 25, 2020
Developing spray-freeze-dried particles containing a hyaluronic acid-coated liposome-protamine-DNA complex for
Kaori Fukushige1, Tatsuaki Tagami2, Munekazu Naito3
1Department of Anatomy, School of Medicine, Aichi Medical University, 1-1 Yazakokarimata, Nagakute, Aichi 480-1195, Japan; Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, Aichi 467-8603, Japan.
Abstract:
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.
