Amphiphilic Poly(amino acid) Copolymers based Xenon Solubility Enhancer for Intravenous Anesthetic

Abstract

Intravenous xenon anesthetic was designed and amphiphilic poly(amino acid)s are selected for xenon solubility enhancer in water. Developing intravenous xenon anesthetic can reduce the loss of xenon gas during the inhalational anesthesia and prevent embolism problem by constructing stable xenon delivery system. Amphiphilic poly(amino acid) copolymers can form self-assembled aggregates in the aqueous solution and xenon could dissolve in hydrophobic domains of aggregates. The N-carboxyanhydrides (NCA) form of α-amino acids was successfully synthesized by Fuchs-Farthing method using triphosgene. Poly(L-lysine)-b-poly(L-leucine)s with three different block ratio (1:1), (1:2), (2:1) were synthesized by ring opening polymerization initiating with hexylamine. And $PEG_{2000}-b-poly(L-leucine)$, $PEG_{5000}-b-poly(L-leucine)$, $PEG_{2000}-b-poly(L-valine)$, $PEG_{2000}-b-poly(L-alanine)$ were synthesized by using mPEG-NH_2 as a macro initiator. The amphiphilic poly(amino acid) copolymers self-aggregates were characterized by measurement of critical aggregation concentration (CAC), size distribution measurement with dynamic light scattering (DLS) and the morphologies of self-aggregates were observed by transmission electron microscopy (TEM) images. The xenon solubility measuring experimental apparatus was designed and successfully set up and tested appropriately. Among the synthesized poly(amino acid) copolymers, the most effective xenon dissolving agent was P(Lys)-P(Leu) (1:1). The xenon solubility results imply that, in the matter of dissolving xenon in water, not only the hydrophobicity of the polymer but also the solubility of the polymer in water is important factor. And the aggregates forming by hydrophobic interaction in the aqueous solution also affected dissolving and binding xenon in hydrophobic domains of aggregates.