Preparation Of PLGA Nanocapsules And Its Application As Gene Delivery Vector

Biocompatible and biodegradable PLGA (poly (lactic-co-glycolic acid) has shown significant potential for gene therapy. With its gradual degradation in vivo, PLGA nanocapsules can slowly release loading drugs, which have shown excellent therapeutic effect. Diphtheria toxins (DT) and its mutants (DT389) can kill multiple tumor cells, which can be used in the treatment of cancer.In this paper, PLGA, PLGA/EGFP and PLGA/DT389 nanocapsules were prepared by W/O/W double emulsion-solvent evaporation method. We examined the factors that may affect the properties of the nanocapsules, which includes the monomer ratio, ultrasonic time and PLGA concentration in W/O emulsion. The nanocapsules prepared were further studied as a cancer gene therapy in vitro.All the nanocapsules prepared are sphere, with smooth surface when examined with the scanning electronic microscopy. DNA loading efficiency and releasing profiles in PBS were measured. The results showed that the loading efficiency increased with increasing ultrasonic time and increasing PLGA concentration. Both PLGA/EGFP and PLGA/DT389 nanocapsules exhibited a sustained-released profile. There was an initial burst release in the first 6 hours and then a gradual release of loaded DNA until 21 days. In addition, all the nanocapsules could protect DNA from the degradation of DNaseâ… .The cell cytotoxicity of the PLGA and PLGA/DT389 nanocapsules were studied by MTT method. PLGA nanocapsules had no toxicity in cultured U251, HEK293 and HepG2 cells. PLGA/DT389 nanocapsules can inhibit the proliferation of the U251 and HepG2 cells, and the inhibition is time and dosage dependent. These results showed that the PLGA/DT389 nanocapsules has the possibility to be used as cancer therapy in future.