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Noninvasive characterization (EPR, ?CT, NMR) of 3D PLA electrospun fiber sponges for controlled drug delivery.

ABSTRACT: Highly porous 3D-scaffolds, made from cut, electrospun PLA fibers, are relatively new and promising systems for controlled drug-delivery applications. Because knowledge concerning fundamental processes of drug delivery from those scaffolds is limited, we noninvasively characterized drug-loading and drug-release mechanisms of these polymer-fiber sponges (PFS). We screened simplified PFS-implantation scenarios with EPR and ?CT to quantify and 3D-visualize the absorption of model-biofluids and an oil, a possible drug-loading liquid. Saturation of PFS (6 × 8 mm, h x d) is governed by the high hydrophobicity of the material and air-entrapment. It required up to 45 weeks for phosphate-buffered saline and 11 weeks for a more physiological, surface-active protein-solution, indicating the slow fluid-uptake of PFS as an effective mechanism to substantially prolong the release of a drug incorporated within the scaffold. Medium-chain triglycerides, as a good wetting liquid, saturated PFS within seconds, suggesting PFS potential to serve as carrier-vessels for immobilizing hydrophobic drug-solutions to define a liquid's 3D-interface. Oil-retention under mechanical stress was therefore investigated. 1H NMR permitted insights into PFS-oil interaction, confirming surface-relaxation and restricted diffusion; both did not influence drug release from oil-loaded PFS. Results facilitate better understanding of PFS and their potential use in drug delivery.

SUBMITTER: Zech J

PROVIDER: S-EPMC7492987 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Noninvasive characterization (EPR, μCT, NMR) of 3D PLA electrospun fiber sponges for controlled drug delivery.

Zech Johanna J Mader Michael M Gündel Daniel D Metz Hendrik H Odparlik Andreas A Agarwal Seema S Mäder Karsten K Greiner Andreas A

International journal of pharmaceutics: X 20200827

Highly porous 3D-scaffolds, made from cut, electrospun PLA fibers, are relatively new and promising systems for controlled drug-delivery applications. Because knowledge concerning fundamental processes of drug delivery from those scaffolds is limited, we noninvasively characterized drug-loading and drug-release mechanisms of these polymer-fiber sponges (PFS). We screened simplified PFS-implantation scenarios with EPR and μCT to quantify and 3D-visualize the absorption of model-biofluids and an o ...[more]

PMID: 32984812

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Project description:In an effort to add to the versatility of three-dimensional scaffolds for tissue engineering applications, recent experimental designs are incorporating biological molecules such as plasmids and proteins within the scaffold structure. Such scaffolds act as reservoirs for the biological molecules of interest while regulating their release over various durations of time. Here, we describe the use of coaxial electrospinning as a means for the fabrication of fiber mesh scaffolds and the encapsulation and subsequent release of a non-viral gene delivery vector over a period of up to 60 days. Various fiber mesh scaffolds containing plasmid DNA (pDNA) within the core and the non-viral gene delivery vector poly(ethylenimine)-hyaluronic acid (PEI-HA) within the sheath of coaxial fibers were fabricated based on a fractional factorial design that investigated the effects of four processing parameters at two levels. Poly(epsilon-caprolactone) sheath polymer concentration, poly(ethylene glycol) core polymer molecular weight and concentration, and the concentration of pDNA were investigated for their effects on average fiber diameter, release kinetics of PEI-HA, and transfection efficiency. It was determined that increasing the values of each of the investigated parameters caused an increase in the average diameter of the fibers. The release kinetics of PEI-HA from the fibers were affected by the loading concentration of pDNA (with PEI-HA concentration adjusted accordingly to maintain a constant nitrogen to phosphorous (N:P) ratio within the complexes). Two-dimensional cell culture experiments with model fibroblast-like cells demonstrated that complexes of pDNA with PEI-HA released from fiber mesh scaffolds could successfully transfect cells and induce expression of enhanced green fluorescent protein (EGFP). Peak EGFP expression varied with the investigated processing parameters, and the average transfection observed was a function of poly(ethylene glycol) (core) molecular weight and concentration. Furthermore, fibroblast-like cells seeded directly onto coaxial fiber mesh scaffolds containing PEI-HA and pDNA showed EGFP expression over 60 days, which was significantly greater than the EGFP expression observed with scaffolds containing pDNA alone. Hence, variable transfection activity can be achieved over extended periods of time upon release of pDNA and non-viral gene delivery vectors from electrospun coaxial fiber mesh scaffolds, with release and subsequent transfection controlled by tunable coaxial fiber mesh fabrication parameters.

Dataset Information

Noninvasive characterization (EPR, ?CT, NMR) of 3D PLA electrospun fiber sponges for controlled drug delivery.

Publications

Noninvasive characterization (EPR, μCT, NMR) of 3D PLA electrospun fiber sponges for controlled drug delivery.

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