PEGylated Amine-Functionalized Poly(ε-caprolactone) for the Delivery of Plasmid DNA
Open Access
- 18 February 2020
- Vol. 13 (4), 898
- https://doi.org/10.3390/ma13040898
Abstract
As a promising strategy for the treatment of various diseases, gene therapy has attracted increasing attention over the past decade. Among various gene delivery approaches, non-viral vectors made of synthetic biomaterials have shown significant potential. Due to their synthetic nature, non-viral vectors can have tunable structures and properties by using various building units. In particular, they can offer advantages over viral vectors with respect to biosafety and cytotoxicity. In this study, a well-defined poly(ethylene glycol)-block-poly(α-(propylthio-N,N-diethylethanamine hydrochloride)-ε-caprolactone) diblock polymer (PEG-b-CPCL) with one poly(ethylene glycol) (PEG) block and one tertiary amine-functionalized cationic poly(ε-caprolactone) (CPCL) block, as a novel non-viral vector in the delivery of plasmid DNA (pDNA), was synthesized and studied. Despite having a degradable polymeric structure, the polymer showed remarkable hydrolytic stability over multiple weeks. The optimal ratio of the polymer to pDNA for nanocomplex formation, pDNA release from the nanocomplex with the presence of heparin, and serum stability of the nanocomplex were probed through gel electrophoresis. Nanostructure of the nanocomplexes was characterized by DLS and TEM imaging. Relative to CPCL homopolymers, PEG-b-CPCL led to better solubility over a wide range of pH. Overall, this work demonstrates that PEG-b-CPCL possesses a range of valuable properties as a promising synthetic vector for pDNA delivery.Funding Information
- National Science Foundation (DMR-1609914)
This publication has 46 references indexed in Scilit:
- Synthesis of Cationic Polylactides with Tunable Charge Densities as Nanocarriers for Effective Gene DeliveryMolecular Pharmaceutics, 2013
- The Role of Liver Sinusoidal Cells in Hepatocyte-Directed Gene TransferThe American Journal of Pathology, 2010
- Well-defined PCL-graft-PDMAEMA prepared by ring-opening polymerisation and click chemistryPolymer Chemistry, 2010
- Viral vectors: from virology to transgene expressionBritish Journal of Pharmacology, 2009
- Biodegradable polymers as biomaterialsProgress in Polymer Science, 2007
- Physical methods for gene transfer: Improving the kinetics of gene delivery into cellsAdvanced Drug Delivery Reviews, 2005
- Immune responses to gene therapy vectors: influence on vector function and effector mechanismsGene Therapy, 2004
- Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivoGene Therapy, 2002
- Nonviral gene therapy: promises and challengesGene Therapy, 2000
- Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transferGene Therapy, 1999