In situ gelling and mucoadhesive polymer vehicles for controlled intranasal delivery of plasmid DNA

Wiley - Tập 59 Số 1 - Trang 144-151 - 2002
Jeong‐Sook Park1, Yu‐Kyoung Oh2, Ho Sung Yoon3, Jung Mogg Kim4, Chong‐Kook Kim1
1College of Pharmacy, Seoul National University, San 56-1, Shinlim-Dong, Kwanak-Ku, Seoul 151-742, South Korea
2Department of Microbiology and Institute of Medical Research, College of Medicine, Pochon CHA University, Kyonggi-do, South Korea
3Department of Anatomy, College of Medicine, Pochon CHA University, Kyonggi-do, South Korea
4Department of Microbiology and Institute of Biomedical Science, College of Medicine, Hanyang University, Seoul, South Korea

Tóm tắt

AbstractNasal administration of plasmid DNA is emerging as a new route of delivery for therapeutic genes and DNA vaccines. To improve the intranasal absorption of plasmid DNA, we designed delivery systems composed of in situ gelling and mucoadhesive polymers. Poloxamers (Pol) were used to provide in situ gelling property. Polycarbophil (PC) or polyethylene oxide (PEO) was used as mucoadhesive polymers. The gelation temperatures of the formulations slightly decreased by the mucoadhesive polymers, but not by plasmid DNA. The in vitro release of plasmid DNA from the gels followed Fickian diffusion. The absorption of plasmid DNA varied with the contents and type of mucoadhesive polymers. Of vehicles, Pol/PC 0.2% showed the highest absorption with an area under the curve value 11‐fold higher than saline, the conventional vehicle. The nasal retention of plasmid DNA was highly prolonged by mucoadhesive polymers. At 3 h postdose, the nasal tissue levels of plasmid DNA given in Pol/PC and Pol/PEO 0.8% were 10‐ and 40‐fold higher relative to saline. The histopathology of nasal tissues was not altered after repeated dosing over 2 weeks. The mRNA expression of plasmid DNA delivered by Pol or Pol/PEO 0.4% was observed in the nasal tissues. These results indicate that the nasal absorption of plasmid DNA can be effectively and safely enhanced by using in situ gelling and mucoadhesive polymer‐based vehicles. © 2001 Wiley Periodicals, Inc. J Biomed Mater Res 59: 144–151, 2002

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Wiley

Tập 59 Số 1

144-151

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