Non-invasive topical drug delivery to spinal cord with carboxyl-modified trifunctional copolymer of ethylene oxide and propylene oxide
2016
Kamalov, Marat I. | Lavrov, Igor A. | Yergeshov, Abdulla A. | Siraeva, Zulfira Y. | Baltin, Maxim E. | Rizvanov, Albert A. | Kuznetcova, Svetlana V. | Petrova, Natalia V. | Savina, Irina N. | Abdullin, Timur I.
In this study the effect of oxidative modification on micellar and drug delivery properties of copolymers of ethylene oxide (EO) and propylene oxide (PO) was investigated. Carboxylated trifunctional copolymers were synthesized in the reaction with chromium(VI) oxide. We found that carboxylation significantly improved the uniformity and stability of polymeric micelles by inhibiting the microphase transition. The cytotoxicity of copolymers was studied in relation to their aggregative state on two cell types (cancer line vs. primary fibroblasts). The accumulation of rhodamine 123 in neuroblastoma SH-SY5Y cells was dramatically increased in the presence of the oxidized block copolymer with the number of PO and EO units of 83.5 and 24.2, respectively. The copolymer was also tested as an enhancer for topical drug delivery to the spinal cord when applied subdurally. The oxidized copolymer facilitated the penetration of rhodamine 123 across spinal cord tissues and increased its intraspinal accumulation. These results show the potential of using oxidized EO/PO based polymers for non-invasive delivery of protective drugs after spinal cord injury.
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