Effect of poly(ethylene glycol) content and formulation parameters on particulate properties and intraperitoneal delivery of insulin from PLGA nanoparticles prepared using the double-emulsion evaporation procedure.

Autor: Haggag YA; a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK.; b Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Tanta , Tanta , Egypt., Faheem AM; c Department of Pharmacy, Health and Well-being , University of Sunderland , Sunderland , UK., Tambuwala MM; a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK., Osman MA; b Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Tanta , Tanta , Egypt., El-Gizawy SA; b Department of Pharmaceutical Technology, Faculty of Pharmacy , University of Tanta , Tanta , Egypt., O'Hagan B; d School of Biomedical Sciences , Ulster University , Cromore Road , Coleraine, Co. Londonderry , UK., Irwin N; a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK., McCarron PA; a School of Pharmacy and Pharmaceutical Sciences, Saad Centre for Pharmacy and Diabetes , Ulster University , Coleraine, Co. Londonderry , UK.
Jazyk: angličtina
Zdroj: Pharmaceutical development and technology [Pharm Dev Technol] 2018 Apr; Vol. 23 (4), pp. 370-381. Date of Electronic Publication: 2017 Mar 06.
DOI: 10.1080/10837450.2017.1295066
Abstrakt: Context: Size, encapsulation efficiency and stability affect the sustained release from nanoparticles containing protein-type drugs.
Objectives: Insulin was used to evaluate effects of formulation parameters on minimizing diameter, maximizing encapsulation efficiency and preserving blood glucose control following intraperitoneal (IP) administration.
Methods: Homogenization or sonication was used to incorporate insulin into poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with increasing poly(ethylene glycol) (PEG) content. Effects of polymer type, insulin/polymer loading ratio and stabilizer in the internal aqueous phase on physicochemical characteristics of NP, in vitro release and stability of encapsulated insulin were investigated. Entrapment efficiency and release were assessed by radioimmunoassay and bicinconnic acid protein assay, and stability was evaluated using SDS-PAGE. Bioactivity of insulin was assessed in streptozotocin-induced, insulin-deficient Type I diabetic mice.
Results: Increasing polymeric PEG increased encapsulation efficiency, while the absence of internal stabilizer improved encapsulation and minimized burst release kinetics. Homogenization was shown to be superior to sonication, with NP fabricated from 10% PEG-PLGA having higher insulin encapsulation, lower burst release and better stability. Insulin-loaded NP maintained normoglycaemia for 24 h in diabetic mice following a single bolus, with no evidence of hypoglycemia.
Conclusions: Insulin-loaded NP prepared from 10% PEG-PLGA possessed therapeutically useful encapsulation and release kinetics when delivered by the IP route.
Databáze: MEDLINE
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