creators_name: Rawat, Sanjay
creators_name: Gupta, Pawan
creators_name: Kumar, Anil
creators_name: Garg, Prabha
creators_name: Suri, C Raman
creators_name: Sahoo, Debendra K
type: article
datestamp: 2015-07-11 05:03:49
lastmod: 2015-07-14 05:05:22
metadata_visibility: show
title: Molecular mechanism of poly(vinyl alcohol) mediated prevention of aggregation and stabilization of insulin in nanoparticles.
ispublished: pub
subjects: QR
keywords: : bovine insulin; poly(lactide-co-glycolide); poly(vinyl alcohol); stability; aggregation; nanoparticles

note: Copyright of this article belongs to ACS Publications
abstract: It is a challenge to formulate polymer based nanoparticles of therapeutic proteins as excipients and process conditions affect stability and structural integrity of the protein. Hence, understanding the protein stability and complex aggregation phenomena is an important area of research in therapeutic protein delivery. Herein we investigated the comparative role of three kinds of surfactant systems (Tween 20:Tween 80), small molecular weight poly(vinyl alcohol) (SMW-PVA), and high molecular weight PVA (HMW-PVA) in prevention of aggregation and stabilization of hexameric insulin in poly(lactide-co-glycolide) (PLGA) based nanoparticle formulation. The nanoparticles were prepared using solid-in-oil-in-water (S/O/W) emulsification method with one of the said surfactant system in inner aqueous phase. The thermal unfolding analysis of released insulin using circular dichroism (CD) indicated thermal stability of the hexameric form. Insulin aggregation monitored by differential scanning calorimetry (DSC) suggested the importance of nuclei formation for aggregation and its prevention by HMW-PVA. Additional guanidinium hydrochloride based equilibrium unfolding and in silico (molecular docking) studies suggested maximum stability of released insulin from formulation containing HMW-PVA (F3). Furthermore, in vivo studies of insulin loaded nanoparticle formulation (F3) in diabetic rats showed its bioactivity. In conclusion, our studies highlight the importance of C-terminal residues of insulin in structural integrity and suggest that the released insulin from formulation containing HMW-PVA in inner aqueous phase was conformationally and thermodynamically stable and bioactive in vivo.
date: 2015-04-06
date_type: published
publication: Molecular pharmaceutics
volume: 12
number: 4
publisher: ACS Publications
pagerange: 1018-30
refereed: TRUE
issn: 1543-8392
official_url: http://pubs.acs.org/doi/abs/10.1021/mp5003653
citation:   Rawat, Sanjay and Gupta, Pawan and Kumar, Anil and Garg, Prabha and Suri, C Raman and Sahoo, Debendra K  (2015) Molecular mechanism of poly(vinyl alcohol) mediated prevention of aggregation and stabilization of insulin in nanoparticles.  Molecular pharmaceutics, 12 (4).  pp. 1018-30.  ISSN 1543-8392     
document_url: http://crdd.osdd.net/open/1664/1/sahoodk2015.pdf