1.Influence of physical properties of carrier on the performance of dry powder inhalers.
Tingting PENG ; Shiqi LIN ; Boyi NIU ; Xinyi WANG ; Ying HUANG ; Xuejuan ZHANG ; Ge LI ; Xin PAN ; Chuanbin WU ;
Acta Pharmaceutica Sinica B 2016;6(4):308-318
Dry powder inhalers (DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance. The purpose of this review is to summarize and illuminate how these factors affect drug-carrier interaction and influence the performance of DPIs.
2.Mesoporous silica nanoparticles for drug and gene delivery.
Yixian ZHOU ; Guilan QUAN ; Qiaoli WU ; Xiaoxu ZHANG ; Boyi NIU ; Biyuan WU ; Ying HUANG ; Xin PAN ; Chuanbin WU
Acta Pharmaceutica Sinica B 2018;8(2):165-177
Mesoporous silica nanoparticles (MSNs) are attracting increasing interest for potential biomedical applications. With tailored mesoporous structure, huge surface area and pore volume, selective surface functionality, as well as morphology control, MSNs exhibit high loading capacity for therapeutic agents and controlled release properties if modified with stimuli-responsive groups, polymers or proteins. In this review article, the applications of MSNs in pharmaceutics to improve drug bioavailability, reduce drug toxicity, and deliver with cellular targetability are summarized. Particularly, the exciting progress in the development of MSNs-based effective delivery systems for poorly soluble drugs, anticancer agents, and therapeutic genes are highlighted.
3.A homogenous nanoporous pulmonary drug delivery system based on metal-organic frameworks with fine aerosolization performance and good compatibility.
Yixian ZHOU ; Boyi NIU ; Biyuan WU ; Sulan LUO ; Jintao FU ; Yiting ZHAO ; Guilan QUAN ; Xin PAN ; Chuanbin WU
Acta Pharmaceutica Sinica B 2020;10(12):2404-2416
Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation,
4.Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis.
Qian YU ; Chang LI ; Qinghui NIU ; Jigang WANG ; Zhaodi CHE ; Ke LEI ; He REN ; Boyi MA ; Yixing REN ; Pingping LUO ; Zhuming FAN ; Huan ZHANG ; Zhaohui LIU ; George L TIPOE ; Jia XIAO
Acta Pharmaceutica Sinica B 2023;13(6):2628-2644
The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.