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1.
Exp Brain Res ; 239(2): 627-638, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33388811

RESUMO

Localized carrier-mediated administration of drugs is a promising approach to treatment of acute phase of spinal cord injury (SCI) as it allows enhanced and/or sustained drug delivery to damaged tissues along with minimization of systemic side effects. We studied the effect of locally applied self-assembling micellar formulation of methylprednisolone succinate (MPS) with trifunctional block copolymer of ethylene oxide and propylene oxide (TBC) on functional recovery and tissue drug content after SCI in rats in comparison with local and systemic administration of MPS alone. Variations in the amplitude of motor evoked responses in the hindlimb muscles induced by epidural stimulation during acute phase of SCI and restoration of movements during chronic period after local vs. systemic application of MPS were evaluated in this study. Results demonstrate that local delivery of MPS in combination with TBC facilitates spinal cord sensorimotor circuitry, increasing the excitability. In addition, this formulation was found to be more effective in improvement of locomotion after SCI compared to systemic administration. LC-MS/MS data shows that the use of TBC carrier increases the glucocorticoid content in treated spinal cord by more than four times over other modes of treatment. The results of this study demonstrate that the local treatment of acute SCI with MPS in the form of mixed micelles with TBC can provide improved therapeutic outcome by promoting drug accumulation and functional restoration of the spinal cord.


Assuntos
Hemissuccinato de Metilprednisolona , Traumatismos da Medula Espinal , Animais , Cromatografia Líquida , Ratos , Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Espectrometria de Massas em Tandem
2.
Colloids Surf B Biointerfaces ; 140: 196-203, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26764102

RESUMO

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.


Assuntos
Compostos de Epóxi/química , Óxido de Etileno/química , Rodamina 123/química , Medula Espinal/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia Líquida de Alta Pressão , Cromo/química , Compostos de Cromo/química , Sistemas de Liberação de Medicamentos/métodos , Fibroblastos/química , Fibroblastos/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Masculino , Microscopia Confocal , Neuroblastoma/química , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Ratos Wistar , Rodamina 123/administração & dosagem , Rodamina 123/farmacocinética , Espectroscopia de Infravermelho com Transformada de Fourier , Medula Espinal/química
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