Development of an enteric nanoparticle of marine sulfated polysaccharide propylene glycol alginate sodium sulfate for oral administration: formulation design, pharmacokinetics and efficacy

Abstract

Objectives: Propylene glycol alginate sodium sulfate (PSS) is poorly absorbed by oral administration due to its large molecular weight and slightly degradability in stomach acidic environment. Here, a novel enteric-coated nano formulation of PSS (enteric PSS-NP) was prepared to improve its bioavailability and efficacy.

Methods: The enteric PSS-NP was prepared by double (W₁ /O/W₂ ) emulsion and solvent evaporation method. The drug release characteristics in vitro were studied in artificial gastrointestinal fluid. And the pharmacokinetics and efficacy of enteric PSS-NP were separately investigated in normal rats and type 2 diabetic db/db mice.

Key findings: The enteric PSS-NP were in spherical shape and exhibited negative zeta potential. The releasing characteristics of enteric PSS-NP in vitro showed that it possessed a strong pH-sensitive release character. Single-dose (50 mg/kg) oral pharmacokinetic study in rat plasma showed that enteric PSS-NP could improve the relative bioavailability significantly compared with PSS solution. Furthermore, the efficacy of enteric PSS-NP in vivo was better than that of PSS solution at equivalent doses.

Conclusions: The study showed that enteric-coated formulation of PSS had the intestinal-targeted absorption and improved pharmacodynamics, which indicated that enteric PSS-NP could be developed into a new formulation product in the future.

Keywords: enteric-coated; in-vitro release; nanoparticles; oral bioavailability; pharmacokinetics.