Sialic Acid-Functionalized PEG-PLGA Microspheres Loading Mitochondrial-Targeting-Modified Curcumin for Acute Lung Injury Therapy.
Feiyang JinDi LiuHui YuJing QiYuchan YouXiaoling XuXuqi KangXiaojuan WangKongjun LuXiaoying YingJian YouYong-Zhong DuJiansong JiPublished in: Molecular pharmaceutics (2018)
Acute lung injury (ALI) is a serious illness without resultful therapeutic methods commonly. Recent studies indicate the importance of oxidative stress in the occurrence and development of ALI, and mitochondria targeted antioxidant has become a difficult and hot topic in the research of ALI. Therefore, a sialic acid (SA)-modified lung-targeted microsphere (MS) for ALI therapy are developed, with triphenylphosphonium cation (TPP)-modified curcumin (Cur-TPP) loaded, which could specifically target the mitochondria, increasing the effect of antioxidant. The results manifest that with the increase of microsphere, lung distribution of microsphere is also increased in murine mice, and after SA modification, the microsphere exhibits the ideal lung-targeted characteristic in ALI model mice, due to SA efficiently targeting to E-selectin expressed on inflammatory tissues. Further investigations indicate that SA/Cur-TPP/MS has better antioxidative capacity, decreases intracellular ROS generation, and increases mitochondrial membrane potential, contributing to a lower apoptosis rate in human umbilical vein endothelial cells (HUVECs) compared to H2O2 group. In vivo efficacy of SA/Cur-TPP/MS demonstrates that the inflammation has been alleviated markedly and the oxidative stress is ameliorated efficiently. Significant histological improvements by SA/Cur-TPP/MS are further proved via HE stains. In conclusion, SA/Cur-TPP/MS might act as a promising drug formulation for ALI therapy.
Keyphrases
- oxidative stress
- cancer therapy
- mass spectrometry
- drug delivery
- multiple sclerosis
- ms ms
- dna damage
- diabetic rats
- ischemia reperfusion injury
- induced apoptosis
- cell death
- reactive oxygen species
- endothelial cells
- lipopolysaccharide induced
- risk assessment
- lps induced
- type diabetes
- emergency department
- endoplasmic reticulum stress
- stem cells
- heat shock
- bone marrow
- vascular endothelial growth factor
- mesenchymal stem cells
- cell cycle arrest