| Title |
Stealth Nanogels of Histinylated Poly Ethyleneimine for Sustained Delivery of Methotrexate in Collagen-Induced Arthritis Model
|
|---|---|
| Published in |
Pharmaceutical Research, May 2015
|
| DOI | 10.1007/s11095-015-1708-0 |
| Pubmed ID | |
| Authors |
SamiraSadat Abolmaali, AliMohammad Tamaddon, Eskandar Kamali-Sarvestani, MohammadJavad Ashraf, Rasoul Dinarvand |
| Abstract |
The study aimed to illustrate application of polycation Stealth nanogels for sustained delivery of methotrexate (MTX) in collagen induced arthritis (CIA) model in C57Bl/6 mice. Nanogel synthesis involves metal ion coordinated self-assembly of PEGylated poly ethyleneimine (L-histidine substituted), chemical crosslinking and subsequent removal of the coordinated metal. The nanogels were characterized by TEM and DLS-zeta potential. Comparative efficacy and pharmacokinetics of the i.v. administred MTX-loaded nanogels were investigated in the CIA model. Inflammation site passive accumulation of the fluorophore-labeled nanogels was tested using in-vivo imaging of mice paw received unilateral injection of lipopolysaccharide. Uniform nanogels (sizes ~40 nm by TEM) were loaded with MTX (entrapment efficiency = 62% and drug loading = 54% at the MTX feeding ratio of 0.3 relative to total molar concentration of the polymer amines). The nanogels exhibited neutral surface charge and an acceptable biocompatibility in terms of albumin aggregation, hemolysis, erythrocyte aggregation and cytotoxicity. Single dose pharmacokinetics of the MTX-loaded nanogels, unlike free drug, showed a sustained plasma profile. When arthritis established as confirmed by histopathology, a remarkable decline of paw swelling and clinical scores was observed. Fluorescence intensity of the nanogels was enhanced about 2.7 folds at the inflamed than control normal ankle. Sustained delivery of MTX and preferential accumulation of the nanogels in inflamed paw might explain the superior clinical outcome of the MTX-loaded nanogels. |
Mendeley readers
The data shown below were compiled from readership statistics for 16 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Iran, Islamic Republic of | 1 | 6% |
| Russia | 1 | 6% |
| Unknown | 14 | 88% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 4 | 25% |
| Researcher | 2 | 13% |
| Student > Ph. D. Student | 2 | 13% |
| Other | 1 | 6% |
| Professor | 1 | 6% |
| Other | 1 | 6% |
| Unknown | 5 | 31% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 3 | 19% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 13% |
| Agricultural and Biological Sciences | 2 | 13% |
| Immunology and Microbiology | 1 | 6% |
| Chemistry | 1 | 6% |
| Other | 2 | 13% |
| Unknown | 5 | 31% |