Cargando…

Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction

We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the borona...

Descripción completa

Detalles Bibliográficos
Autores principales: Morey, Mangesh, Srivastava, Akshay, Pandit, Abhay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825127/
https://www.ncbi.nlm.nih.gov/pubmed/33418878
http://dx.doi.org/10.3390/pharmaceutics13010062
_version_ 1783640234853924864
author Morey, Mangesh
Srivastava, Akshay
Pandit, Abhay
author_facet Morey, Mangesh
Srivastava, Akshay
Pandit, Abhay
author_sort Morey, Mangesh
collection PubMed
description We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological pH was achieved by copolymerization of dimethyl aminoethyl methacrylate (DMAEMA) with acrylamidophenylboronic acid (AAPBA) and the formation of a complex with polyvinylalcohol (PVA) which is governed by cis-diol interactions. The shift in hydrodynamic diameter of SMPs was observed and correlated with increasing glucose concentrations at a physiological pH. Optimal transfection was observed for a 5 µg dose of the gaussia luciferase reporter gene in NIH3T3 cells without any adverse effect on cellular viability. The destabilization of the AAPBA–PVA complex by interacting with glucose allowed the release of encapsulated bovine serum albumin (BSA) in a glucose-responsive manner. In total, 95% of BSA was released from SMPs at a 50 mM glucose concentration after 72 h. A two-fold increase in transfection was observed in 50 mM glucose compared to that of 10 mM glucose.
format Online
Article
Text
id pubmed-7825127
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-78251272021-01-24 Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction Morey, Mangesh Srivastava, Akshay Pandit, Abhay Pharmaceutics Article We report a physiologically stable and cytocompatible glucose-responsive nonviral gene delivery system made up of boronate functionalized polymeric material. Herein, we utilize boronate cis-diol interactions to develop a glucose-responsive submicron particle (SMP) system. The stability of the boronate interaction at a physiological pH was achieved by copolymerization of dimethyl aminoethyl methacrylate (DMAEMA) with acrylamidophenylboronic acid (AAPBA) and the formation of a complex with polyvinylalcohol (PVA) which is governed by cis-diol interactions. The shift in hydrodynamic diameter of SMPs was observed and correlated with increasing glucose concentrations at a physiological pH. Optimal transfection was observed for a 5 µg dose of the gaussia luciferase reporter gene in NIH3T3 cells without any adverse effect on cellular viability. The destabilization of the AAPBA–PVA complex by interacting with glucose allowed the release of encapsulated bovine serum albumin (BSA) in a glucose-responsive manner. In total, 95% of BSA was released from SMPs at a 50 mM glucose concentration after 72 h. A two-fold increase in transfection was observed in 50 mM glucose compared to that of 10 mM glucose. MDPI 2021-01-06 /pmc/articles/PMC7825127/ /pubmed/33418878 http://dx.doi.org/10.3390/pharmaceutics13010062 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Morey, Mangesh
Srivastava, Akshay
Pandit, Abhay
Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction
title Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction
title_full Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction
title_fullStr Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction
title_full_unstemmed Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction
title_short Glucose-Responsive Gene Delivery at Physiological pH through Tertiary-Amine Stabilized Boronate-PVA Particles Synthesized by One-Pot Reaction
title_sort glucose-responsive gene delivery at physiological ph through tertiary-amine stabilized boronate-pva particles synthesized by one-pot reaction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825127/
https://www.ncbi.nlm.nih.gov/pubmed/33418878
http://dx.doi.org/10.3390/pharmaceutics13010062
work_keys_str_mv AT moreymangesh glucoseresponsivegenedeliveryatphysiologicalphthroughtertiaryaminestabilizedboronatepvaparticlessynthesizedbyonepotreaction
AT srivastavaakshay glucoseresponsivegenedeliveryatphysiologicalphthroughtertiaryaminestabilizedboronatepvaparticlessynthesizedbyonepotreaction
AT panditabhay glucoseresponsivegenedeliveryatphysiologicalphthroughtertiaryaminestabilizedboronatepvaparticlessynthesizedbyonepotreaction