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

摘要

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 (W 1 /O/W 2 ) 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.