Anti-Aβ-Scfv-Loaded Polymeric Nano-Micelles With Enhanced Plasma Stability Publisher Pubmed



Sotoudegan F¹ ; Sotoudegan F¹ ; Talebkhan Garoosi Y¹ ; Afshar SH³ ; Barkhordari F¹ ; Davami F¹ Show Affiliations
Source: Journal of Pharmacy and Pharmacology Published:2021

Abstract

Objectives: Immunotherapy using recombinant monoclonal antibodies specifically Anti-amyloid-beta (Anti-Aβ) scFv is envisaged as an appropriate therapeutic for Alzheimer through reduction of amyloid-beta aggregation. The solubilization of therapeutics using polymeric micelles facilitates an improved bioavailability and extended blood half-life. In this study, the optimum production condition for Anti-amyloid-beta (Anti-Aβ) scFv was obtained. To increase the stability of plasma, Anti-Aβ-loaded polymeric micelles were synthesized. Methods: Escherichia coli SHuffle expression strain was used and purified by Ni-NTA. Pluronics P85 and F127 micelles were used for the Anti-Aβ delivery and were characterized in terms of morphology, drug loading and drug release in phosphate buffer and artificial cerebrospinal fluid. The stability profile was quantified at 4°C over a 30 days storage period. The stability in human plasma was also evaluated. Key findings: Proteins expressed in SHuffle resulted in increased levels of protein expression and solubility. Low critical micelle concentration value and high micelle encapsulation efficiency (<200 nm) achieved via direct dissolution method. Anti-Aβ-loaded micelles were around 2.2-fold more stable than Anti-Aβ in plasma solution. A sustained in-vitro release of Anti-Aβ from micelles was observed. Conclusions: Results confirmed that Pluronic-micelles pose benefits as a nano-carrier to increase the stability of Anti-Aβ scFvin in the plasma. © 2021 The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.