title: Non-invasive topical drug delivery to spinal cord with carboxyl-modified trifunctional copolymer of ethylene oxide and propylene oxide.
abstract: 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.
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Marat I
authors.initials: MI
authors.lastname: Kamalov
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia. Electronic address: igor.lavrov@gmail.com.
authors.forename: Igor A
authors.initials: IA
authors.lastname: Lavrov
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Abdulla A
authors.initials: AA
authors.lastname: Yergeshov
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Zulfira Y
authors.initials: ZY
authors.lastname: Siraeva
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Maxim E
authors.initials: ME
authors.lastname: Baltin
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Albert A
authors.initials: AA
authors.lastname: Rizvanov
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Kuznetcova
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia.
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Petrova
authors.affiliation: School of Pharmacy and Biomolecular Sciences, University of Brighton, Huxley Building, Lewes Road, Brighton BN2 4GJ, UK.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Savina
authors.affiliation: Kazan (Volga Region) Federal University, 18 Kremlyovskaya St., 420008 Kazan, Russia. Electronic address: tabdulli@gmail.com.
authors.forename: Timur I
authors.initials: TI
authors.lastname: Abdullin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002857:Chromium / Q000737:chemistry; D017608:Chromium Compounds / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D004852:Epoxy Compounds / Q000737:chemistry*; D005027:Ethylene Oxide / Q000737:chemistry*; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D018613:Microscopy, Confocal; D009447:Neuroblastoma / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D020112:Rhodamine 123 / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared; D013116:Spinal Cord / Q000737:chemistry / Q000378:metabolism*
chemical_list: D017608:Chromium Compounds; D004852:Epoxy Compounds; D002857:Chromium; C074702:chromium hexavalent ion; D020112:Rhodamine 123; D005027:Ethylene Oxide; C023600:chromic oxide; C009068:propylene oxide
keywords: Amphiphilic polymers; Drug delivery; Micelles; Neural cells; Oxidative modification; Spinal cord; Traumatic injury; Trifunctional copolymers of ethylene oxide and propylene oxide