Pengli Li1,2,3, Jiejie Hao1,2, Haihua Li1,2, Huashi Guan1,2,3,4, Chunxia Li1,2,4. 1. Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao, China. 2. Shandong Provincial Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, China. 3. Marine Biomedical Research Institute of Qingdao, Qingdao, China. 4. Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology, Ocean University of China, Qingdao, China.
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.
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.
Authors: Nasrul Wathoni; An Ny Nguyen; Agus Rusdin; Abd Kakhar Umar; Ahmed Fouad Abdelwahab Mohammed; Keiichi Motoyama; I Made Joni; Muchtaridi Muchtaridi Journal: Drug Des Devel Ther Date: 2020-10-21 Impact factor: 4.162