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The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles.

ABSTRACT: Novel submicron core-shell-structured chitosan-based composite particles encapsulated with enhanced green fluorescent protein plasmids (pEGFP) were prepared by complex coacervation method. The core was pEGFP-loaded thiolated N-alkylated chitosan (TACS) and the shell was pH- and temperature-responsive hydroxybutyl chitosan (HBC). pEGFP-loaded TACS-HBC composite particles were spherical, and had a mean diameter of approximately 120 nm, as measured by transmission electron microscopy and particle size analyzer. pEGFP showed sustained release in vitro for >15 days. Furthermore, in vitro transfection in human embryonic kidney 293T and human cervix epithelial cells, and in vivo transfection in mice skeletal muscle of loaded pEGFP, were investigated. Results showed that the expression of loaded pEGFP, both in vitro and in vivo, was slow but could be sustained over a long period. pEGFP expression in mice skeletal muscle was sustained for >60 days. This work indicates that these submicron core-shell-structured chitosan-based composite particles could potentially be used as a gene vector for in vivo controlled gene transfection.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4211910 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe diversified combination of nanostructure and material has received considerable attention from researchers to exploit advanced functional materials. In drug delivery systems, the hydrophilicity and sustained-release drug properties are in opposition. Thus, difficulties remain in the simultaneous improve sustained-release drug properties and increase the hydrophilicity of materials.MethodsIn this work, we proposed a modified triaxial electrospinning strategy to fabricate functional core-shell fibres, which could elaborate design of shell component for manipulating the sustained-release drug. Cellulose acetate (CA) was designed as the main polymeric matrix, whereas polyethylene glycol (PEG) was added as a hydrophilic material in the middle layer. Cur, as a model drug, was stored in the inner layer.ResultsScanning electron microscopy (SEM) results and transmission electron microscopy (TEM) demonstrated that the cylindrical F2-F4 fibres had a clear core-shell structure. The model drug Cur in fibres was verified in an amorphous form during the X-ray diffraction (XRD) patterns, and Fourier transformed infrared spectroscopy (FTIR) results indicated good compatibility with the CA matrix. The water contact angle test showed that functional F2-F4 fibres had a high hydrophilic property in 120 s and the control sample F1 needed over 0.5 h to obtain hydrophilic property. In the initial stage of moisture intrusion into fibres, the quickly dissolved PEG component guided the water molecules and rapidly eroded the internal structure of functional fibres. The good hydrophilicity of F2-F4 fibres brought relatively excellent swelling rate around 4600%. Blank outer layer of functional F2 fibres with 1% PEG created an exciting opportunity for providing a 96 h sustained-release drug profile, while F3 and F4 fibres with over 3% PEG provided a 12 h modified drug release profile to eliminate tailing-off effect.ConclusionHere, the functional F2-F4 fibres had been successfully produced by using the advanced modified triaxial electrospinning nanotechnology with different polymer matrices. The simple strategy in this work has remarkable potential to manipulate hydrophilicity and sustained release of drug carriers, meantime it can also enrich the preparation approaches of functional nanomaterials.

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The sustained-release behavior and in vitro and in vivo transfection of pEGFP-loaded core-shell-structured chitosan-based composite particles.

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