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

J Pharm Pharmacol. 2018 Jun;70(6):740-748. doi: 10.1111/jphp.12902. Epub 2018 Mar 12.

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.

MeSH terms

  • Administration, Oral
  • Alginates / chemistry
  • Alginates / pharmacokinetics*
  • Alginates / pharmacology*
  • Animals
  • Biological Availability
  • Blood Glucose / drug effects*
  • Drug Liberation
  • Female
  • Intestinal Absorption
  • Male
  • Metformin
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Particle Size
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacokinetics*
  • Polysaccharides / pharmacology*
  • Rats
  • Sulfates / chemistry
  • Surface Properties
  • Tablets, Enteric-Coated / chemistry
  • Tablets, Enteric-Coated / pharmacokinetics
  • Tablets, Enteric-Coated / pharmacology

Substances

  • Alginates
  • Blood Glucose
  • Polysaccharides
  • Sulfates
  • Tablets, Enteric-Coated
  • propylene glycol alginate sodium sulfate
  • Metformin