Doxorubicin-loaded highly porous large PLGA microparticles as a sustained- release inhalation system for the treatment of metastatic lung cancer

Biomaterials
Insoo KimYu Seok Youn

Abstract

Doxorubicin-loaded highly porous large PLGA microparticles (Dox PLGA MPs) were prepared using a w/o/w double emulsification method using ammonium bicarbonate effervescent salt. The prepared Dox PLGA MPs were characterized by particle size analysis, scanning electron microscopy, and confocal microscopy. In vitro cytotoxicity to B16F10 melanoma cells and lung deposition in C57BL/6 mice were examined, and finally the anti-tumor efficacy of pulmonary administered Dox PLGA MPs was evaluated in a mouse model of B16F10 melanoma metastasis. Results showed that Dox PLGA MPs were highly porous, had high encapsulation efficiency, and good aerosolization characteristics. Doxorubicin was gradually released from Dox PLGA MPs over 2 weeks, and after pulmonary administration, Dox PLGA MPs were deposited in lungs and remained in situ for up to 14 days. Furthermore, exposure to Dox PLGA MPs killed B16F10 cells in vitro within 24 h. In particular, tumors in B16F10-implanted mice treated with Dox PLGA MPs were remarkably smaller in terms of mass and number than those in non-treated B16F10-implanted mice. We believe that doxorubicin-loaded highly porous large PLGA microparticles have great potential as a long-term inhalation agent for the treatment...Continue Reading

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