Targeting delivery of simvastatin using ICAM-1 antibody-conjugated nanostructured lipid carriers for acute lung injury therapy.
Acute lung injury (ALI) is a critical illness without effective therapeutic modalities currently. Recent studies indicated potential efficacy of statins for ALI, while high-dose statins was suggested to be significant for attenuating inflammation in vivo. Therefore, a lung-targeted drug delivery system (DDS) delivering simvastatin (SV) for ALI therapy was developed, attempting to improve the disease with a decreased dose and minimize potential adverse effects. SV-loaded nanostructured lipid carriers (SV/NLCs) with different size were prepared primarily. With particle size increasing from 143.7 nm to 337.8 nm, SV/NLCs showed increasing drug-encapsulated efficiency from 66.70% to 91.04%. Although larger SV/NLCs exhibited slower in vitro cellular uptake by human vascular endothelial cell line EAhy926 at initial stage, while in vivo distribution demonstrated higher pulmonary accumulation of the larger ones. Thus, the largest size SV/NLCs (337.8 nm) were conjugated with intercellular adhesion molecule 1 (ICAM-1) antibody (anti-ICAM/SV/NLCs) for lung-targeted study. The anti-ICAM/SV/NLCs exhibited ideal lung-targeted characteristic in lipopolysaccharide-induced ALI mice. In vivo i.v. administration of anti-ICAM/SV/NLCs attenuated TNF-α, IL-6 and inflammatory cells infiltration more effectively than free SV or non-targeted SV/NLCs after 48-h administration. Significant histological improvements by anti-ICAM/SV/NLCs were further revealed by H&E stain. Therefore, ICAM-1 antibody-conjugated NLCs may represent a potential lung-targeted DDS contributing to ALI therapy by statins.
a Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , PR China and.
Shu-Juan
SJ
Li
a Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , PR China and.
Xiao-Juan
XJ
Wang
a Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , PR China and.
Jing-Bo
JB
Hu
a Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , PR China and.
Xu-Qi
XQ
Kang
b Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou , PR China.
Li
L
Chen
a Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , PR China and.
Xiao-Ling
XL
Xu
a Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , PR China and.
Xiao-Ying
XY
Ying
b Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University , Hangzhou , PR China.
Sai-Ping
SP
Jiang
a Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University , Hangzhou , PR China and.
Yong-Zhong
YZ
Du
D000072283:A549 Cells; D055371:Acute Lung Injury / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011897:Random Allocation; D019821:Simvastatin / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism
D000906:Antibodies; D004337:Drug Carriers; D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin
ICAM-1; Lung targeting; acute lung injury; nanostructured lipid carriers; simvastatin delivery