Non-invasive topical drug delivery to spinal cord with carboxyl-modified trifunctional copolymer of ethylene oxide and propylene oxide

摘要

In this study the effect of oxidative modification on micellar and drug deliveryproperties of copolymers of ethylene oxide (EO) and propylene oxide (PO) wasinvestigated. Carboxylated trifunctional copolymers were synthesized in the reaction withchromium oxide (VI). We found that carboxylation significantly improved the uniformityand stability of polymeric micelles by inhibiting the microphase transition. Thecytotoxicity of copolymers was studied in relation to their aggregative state on two celltypes (cancer line vs. primary fibroblasts). The accumulation of rhodamine 123 inneuroblastoma SH-SY5Y cells was dramatically increased in the presence of the oxidizedblock copolymer with the number of PO and EO units of 83.5 and 24.2, respectively. Thecopolymer was also tested as an enhancer for topical drug delivery to the spinal cordwhen applied subdurally. The oxidized copolymer facilitated the penetration ofrhodamine 123 across spinal cord tissues and increased its intraspinal accumulation.These results show the potential of using oxidized EO/PO based polymers for noninvasivedelivery of protective drugs after spinal cord injury.