Anti-Aβ-scFv-loaded polymeric nano-micelles with enhanced plasma stability.

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.