Novel stimuli responsive targeted drug delivery formulations for lung cancer therapy

Abstract

The tumor targeting and stimuli responsiveness behaviour of intelligent drug delivery systems imparts effective therapeutic delivery and decreases the toxicity of conventional chemotherapeutic agents in offtarget organs. In this research work, matrix metalloproteinase (MMP) responsive cisplatin loaded mesoporous silica nanoparticles, cisplatin loaded gelatin nanoparticles, and carboplatin loaded PLGA nanoparticles were developed and assessed for its on-demand controlled drug delivery in lung cancer therapy. MMPs are protease enzymes and over-expressed in tumorous tissues in all the stages of cancer. All these nanoparticles have attracted significant attraction in recent years as a potential drug carrier because of its excellent biocompatibility and versatile physicochemical properties desirable to deliver the drug. Cisplatin and carboplatin is drug of choice for the lung cancer therapy but they show toxicity in offtarget organs. So, to overcome this problem Cisplatin and carboplatin were incorporated in MMP enzymeresponsive delivery carrier. Hence, the tumor tissue would help to release of cisplatin/carboplatin in response of over-expressed MMP enzymes and ensures controlled drug release. The synthesized nanocarriers have shown enzyme triggered drug release and favorable endocytosis. The efficacy of nanocarriers significantly increased in presence of MMP-2 enzyme against A549 cells. It has significantly enhanced reactive oxygen species generation, cell cycle arrest in S and G2/M phase, and apoptosis. PLGA based nanocarrier had shown excellent in-vivo activity in mice model f lung cancer. Therefore, MMP enzyme-responsive delivery carrier promises a pragmatic approach to construct a receptor targeting and an ondemand drug delivery system to efficiently deliver the drug at the tumor site only. newline