Matrix metalloproteinase 2/9-triggered-release micelles for inhaled drug delivery to treat lung cancer: preparation and in vitro/in vivo studies

International Journal of Nanomedicine
Xiaofei WangXiaoling Fang

Abstract

Improvement in drug accumulation in the lungs through inhalation administration and high expression of MMP2 and MMP9 in lung tumors have both been widely reported. MMP2/9-triggered-release micelles were constructed and in vitro and in vivo studies of inhalation administration against lung tumor carried out. Pluronic P123 (P123) was modified with GPLGIAGQ-NH2 (GQ8) peptide to obtain P123-GQ8 (PG). MMP2/9-triggered-release micelles were constructed using PG and succinylated gelatin (SG) and loading paclitaxel (Ptx). To study biodistribution of micelles, DiR encapsulated in micelles was dosed to rats via intravenous injection or inhalation before ex vivo imaging for detecting DiR quantity in lungs. And B16F10 lung cancer-bearing nude mice were chosen as animal models to evaluate in vivo efficacy of MMP2/9-triggered-release micelles. Ptx-release efficiency from PG-SG-Ptx micelles was MMP2/9-concentration-dependent. For A549 cells, PG-SG-Ptx cytotoxicity was significantly greater (P<0.001) compared to P123-Ptx. Aerosol inhalation was chosen as the method of administration. In biodistribution experiment, DiR quantity in lungs was 5.8%±0.4% of that in major organs, while the ratio was 38.8%±0.5% for inhalation. For B16F10 lung cancer-...Continue Reading

Citations

Jan 29, 2019·Current Topics in Medicinal Chemistry·Yanan LiFeifei An
Sep 2, 2020·Journal of Materials Chemistry. B, Materials for Biology and Medicine·Youbei QiaoHong Wu
Sep 3, 2021·Advanced Drug Delivery Reviews·Alba García-FernándezRamón Martínez-Máñez

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Datasets Mentioned

BETA
GM6001

Methods Mentioned

BETA
nuclear magnetic resonance
dynamic light scattering
fluorescence microscopy
NMR

Software Mentioned

Pluronic

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