Journal article
Encapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In Vivo
AAPS PharmSciTech, Vol.22(2), pp.69-69
02/09/2021
DOI: 10.1208/s12249-021-01932-z
PMID: 33565009
Abstract
Encapsulating genetic material into biocompatible polymeric microparticles is a means to improving gene transfection while simultaneously decreasing the tendency for inflammatory responses; and can be advantageous in terms of delivering material directly to the lungs via aerosolization for applications such as vaccinations. In this study, we investigated the advantages of using polymeric microparticles carrying the luciferase reporter gene in increasing transfection efficiency in the readily transfectable HEK293 cell line and the difficult to transfect RAW264.7 cell line. The results indicated that there was a limit to the ratio of nitrogen in polyethylenimine (PEI) to phosphate in DNA (N/P ratio) beyond which further increases in transgene expression no longer, or only marginally, occurred. Microparticles encapsulating PEI:DNA nanoplexes induced cellular toxicity in a dose-dependent manner. PEGylation increased transgene expression, likely related to enhanced degradation of particles. Furthermore, intra-tracheal instillation in rats allowed us to investigate the inflammatory response in the lung as a function of PEGylation, porosity, and size. Porosity did not influence cell counts in bronchoalveolar lavage fluid in the absence of PEG, but in particles containing PEG, non-porous particles recruited fewer inflammatory cells than their porous counterparts. Finally, both 1 μm and 10 μm porous PLA-PEG particles recruited more neutrophils than 4 μm particles. Thus, we have shown that PEGylation and lack of porosity are advantageous for faster release of genetic cargo from microparticles and a reduced inflammatory response, respectively.
Details
- Title: Subtitle
- Encapsulating Polyethyleneimine-DNA Nanoplexes into PEGylated Biodegradable Microparticles Increases Transgene Expression In Vitro and Reduces Inflammatory Responses In Vivo
- Creators
- Treniece L Terry - Iowa City, Iowa 52242 USABrittany E Givens - Iowa City, Iowa 52242 USAAndrea Adamcakova-Dodd - University of Iowa, Occupational and Environmental HealthPeter S Thorne - University of Iowa, Occupational and Environmental HealthVictor G. J Rodgers - Riverside, California 92521 USAAliasger K Salem - University of Iowa, Pharmaceutical Sciences and Experimental Therapeutics
- Resource Type
- Journal article
- Publication Details
- AAPS PharmSciTech, Vol.22(2), pp.69-69
- DOI
- 10.1208/s12249-021-01932-z
- PMID
- 33565009
- NLM abbreviation
- AAPS PharmSciTech
- ISSN
- 1530-9932
- eISSN
- 1530-9932
- Publisher
- Springer International Publishing; Cham
- Language
- English
- Date published
- 02/09/2021
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Civil and Environmental Engineering; Occupational and Environmental Health; Stead Family Department of Pediatrics; Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984077788602771
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