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Albumin-Conjugated Lipid-Based Multilayered Nanoemulsion Improves Drug Specificity and Anti-Inflammatory Potential at the Spinal Cord Injury gSite after Intravenous Administration

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Abstract

Albumin-conjugated multilayered nanoemulsion (albumin-MNE) of methyl prednisolone (MP) was developed to ensure the specificity of the drug at the spinal cord injury (SCI) site. MNE was prepared by emulsification followed by ionic deposition of oppositely charged polymer followed by albumin conjugation using N-hydroxysuccinimide. Prepared nanoemulsion was characterized for particle size, polydispersity index (PDI), zeta potential (Zp), pH, viscosity, and entrapment efficiency. It was further evaluated for shape and morphological analysis, in vitro release, cell viability, and in vivo efficacy against post SCI-like conditions in terms of behavioral assessment, histopathological evaluation, and immunoflorescence assay of the histological sections showing Bax-driven apoptosis. Entrapment efficiency, particle size, PDI, and Zp of spherical-shaped, smooth-surfaced MNE droplets were found to be 68.9%, 83.2 ± 14.4 nm, 0.231, and + 62.7 mV, respectively. In vitro release of MP from MNE and albumin-MNE was observed to be 68.5 and 72.2% after 96th hour of the study. MNE showed higher viability of astrocytes than MP solution. Albumin-MNE improved behavior of SCI rat and histopathological conditions in a very effective manner when compared with MNE. Immunoflorescence assay reveals explicit decline in mitochondrial-mediated apoptosis by sub-cellular upregulation of Bax at spinal cord injury site. In conclusion, albumin-MNE delivered MP specifically at SCI site and avoided its instant availability inside astrocytes culture. On account of which the chitosan stabilized, lecithin-emulsified, multilayered nanoemulsion of MP depicts higher efficacy and safety than MNE and may offer safe and effective mean for the treatment of post SCI-like conditions in human.

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Authors and Affiliations

  1. Department of Orthopedics, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, Jiangsu, 223300, China

    Xiao-Gang Chen, Shou-Guo Wang & Hong-Hui Tang

  2. Department of Gynecology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, Jiangsu, 223300, China

    Fu Hua

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  1. Xiao-Gang Chen
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  2. Fu Hua
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  4. Hong-Hui Tang
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Correspondence to Shou-Guo Wang.

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Chen, XG., Hua, F., Wang, SG. et al. Albumin-Conjugated Lipid-Based Multilayered Nanoemulsion Improves Drug Specificity and Anti-Inflammatory Potential at the Spinal Cord Injury gSite after Intravenous Administration. AAPS PharmSciTech 19, 590–598 (2018). https://doi.org/10.1208/s12249-017-0867-1

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  • DOI: https://doi.org/10.1208/s12249-017-0867-1

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