A Combinatorial Statistical Design Approach to Optimize the Nanostructured Cubosomal Carrier System for Oral Delivery of Ubidecarenone for Management of Doxorubicin-Induced Cardiotoxicity: In Vitro-In Vivo Investigations.

作者: Abdul Muheem , Faiyaz Shakeel , Musarrat Husain Warsi , Gaurav Kumar Jain , Farhan Jalees Ahmad

DOI: 10.1016/J.XPHS.2017.05.026

关键词: CardiotoxicityChromatographySuperoxide dismutaseBioavailabilityLactate dehydrogenaseCreatineChemistryLipid peroxidationParticle sizeStereochemistryZeta potential

摘要: Abstract Present work aims to optimize and characterize orally administered, ubidecarenone (UDC)-loaded glycerylmonooleate-based cubosome (GCBMs) phytantriol based cubosomes (PCBMs) for effective management of doxorubicin-induced cardiotoxicity enhance bioavailability UDC. Formulations optimized using statistical hybrid-design approach exhibited particle size 152.0 ± 1.78 248.8 1.83 nm, polydispersity index 0.183 0.021 0.225 0.018 with zeta potential of −26.8 0.76 and −23.3 0.22 mV percentage entrapment efficiency (% EE) 92.3 4.99% 94.7 5.67%, GCBMs PCBMs, respectively. High-resolution transmission electron microscopy revealed agreement the shows discrete cubic geometry particles, while small-angle X-ray scattering analysis confirmed primitive (Im3m) diamond (Pn3m) type crystalline self-assemble structure particles. The comparative profiles UDC from PCBMs (AUC 0→∞  = 19,546.8 512.88 ng·h/L 27,961.99 602.46 PCBMs) were approximately 6.5- 7.0-fold higher than that suspension 3132.806 405.44 ng·h/L). Cardioprotective assessment showed a significant increase in superoxide dismutase β-glutathione peroxidase levels, decrease level catalase, creatine kinase-MB isoenzyme, lactate dehydrogenase, lipid peroxidation was observed animals pre-treated developed CBMs. Histopathology studies no damage, infiltrated cells, signs fibrosis CBM-treated groups.

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