Biomimetic synthesis of proline-derivative templated mesoporous silica for increasing the brain distribution of diazepam and improving the pharmacodynamics of nimesulide

Drug Delivery

Sanming Li¹  Jialiang Cong¹  Hongzhuo Liu¹  Chen Wei¹  Heran Li²  Jing Li²  Jianxin Wang²  Mingshi Yang³ 

[1] School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China;Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China;Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, China;Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmar;

关键词: Mesoporous silica nanoparticle;    brain targeting;    biomimetic synthesis nanomaterial;    drug delivery;   

DOI  :  10.1080/10717544.2017.1359863

来源: Taylor & Francis

【 摘 要 】

Herein a new kind of proline-derivative templated mesoporous silica with curved channels (CMS) was biomimetically synthesized and applied as carrier to improve the drug dissolution and bioavailability of hydrophobic diazepam (DZP) and nimesulide (NMS). Drugs can be incorporated into CMS with high efficiency; during this process, they successfully transformed to amorphous phase. As a result, the dissolution rate of DZP and NMS was significantly improved. Biodistribution study confirmed that CMS converted DZP distribution in mice with the tendency of lung targeting and brain targeting. At 45 min postadministration, the concentrations of DZP in plasma, lung and brain were 8.57-fold, 124.94-fold and 19.55-fold higher from 1:3 DZP/CMS sample than that of pure DZP sample, respectively. At 90 min postadministration, the content of DZP in brain was 62.31-fold higher for 1:3 DZP/CMS sample than that of pure DZP. Besides, the anti-inflammatory and analgesic effects of 1:3 NMS/CMS were systematic evaluated using mouse ankle swelling test (MAST), mouse ear swelling test (MEST) and mouse writhing test (MWT). The results indicated that after incorporating into CMS, the therapeutic effects of NMS were obviously improved, and the inhibition rates of 1:3 NMS/CMS in all pharmacodynamics tests varied from 102.2% to 904.3%.

【 授权许可】

CC BY