Original ArticleTargeted drug delivery to ischemic stroke via chlorotoxin-anchored, lexiscan-loaded nanoparticles
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Section snippets
Synthesis of PLGA–PLL
Synthesis of PLGA–PLL was accomplished via coupling using dicyclohexyl carbodiimide as previously reported.29, 30, 31 In a typical reaction, PLGA (3 g, 50:50 PLGA Acid End Group; i.v. ~ 0.67 dL/g; Absorbable Polymers: Pelham, AL) and 200 mg poly(ε-carbobenzoxyl-L-lysine) (PLL) in 5 M excess (1000-4000 MW) were dissolved in 6 mL dimethlyformamide in a dry round-bottom flask under argon. Dicyclohexyl carbodiimide (58 mg) and 0.31 mg dimethylaminopyridine were dissolved in 2 mL dimethlyformamide under
Design, synthesis and characterization of NPs
The schematic diagram of a typical PLGA-CTX/LEX NP was illustrated in Figure 1, A. NPs were synthesized through double emulsion procedures using PLL-conjugated PLGA as the starting material. The resulting NPs were modified with NHS-PEG-Mal to display PEG and maleimide functional groups. LEX was encapsulated in NPs during the emulsion with an entrapment efficiency of 33.8% and a loading efficiency of 0.8%. CTX was conjugated to the surface of NPs through the maleimide groups at a ratio of 800
Discussion
In the present study, we proposed an innovative approach for drug delivery to the ischemic microenvironment inside the brain through the combination of the traditional ligand-mediated approach, with a novel autocatalysis mechanism, which is designed to augment delivery efficiency. Our results demonstrated that, the resulting NPs synthesized based on this approach, PLGA-CTX/LEX NPs, efficiently crossed the BBB in the ischemic brain with high specificity. In contrast, NPs engineered either
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Cited by (0)
This work was supported by NIHNS095817, NS095147AHA15GRNT25290018, and a Yale Center for Clinical Investigation CTSA Scholar Award (UL1 TR000142). QC, DT, XG and ZC were partially supported by scholarships from the Chinese Scholarship Council.
Conflict of interest: S.M.S. is a co-founder of Axerion Therapeutics seeking to develop the Nogo-NogoReceptor-based medicines for Neural Repair, and prion protein-based medicines for Alzheimer disease.