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  • Title: Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for positively charged drugs.
    Author: Takeuchi I, Takeshita T, Suzuki T, Makino K.
    Journal: Colloids Surf B Biointerfaces; 2017 Dec 01; 160():520-526. PubMed ID: 29017147.
    Abstract:
    Recently, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles prepared using a combination of an antisolvent diffusion method with preferential solvation was shown to be beneficial for the iontophoretic transdermal delivery of therapeutic agents. Also, this preparation method can contain a hydrophilic drug. However, since PLGA nanoparticles were negatively charged, it was difficult to apply iontophoresis for positively charged hydrophilic drugs. In this study, we prepared positively charged PLGA nanoparticles containing donepezil hydrochloride (DP). DP was used as a positively charged hydrophilic drug model. The PLGA nanoparticles were coated with chitosan hydroxypropyltrimonium chloride. The average particle diameter of the nanoparticles was 117.7±60.6nm and the surface charge number density changed from negative to positive. Ex vivo skin accumulation study was carried out using abdominal rat skin and a Franz-type diffusion cell with/without iontophoresis. When iontophoresis was applied, the DP concentration in the rat skin of chitosan-coated PLGA nanoparticles was 2.2 times higher than that of non-coated PLGA nanoparticles. This indicated that chitosan-coated PLGA nanoparticles were suitable for iontophoresis. To investigate the transdermal delivery route of the nanoparticles, we prepared chitosan-coated PLGA nanoparticles containing DP, coumarin-6, and rhodamine 6G. Coumarin-6 and rhodamine 6G were used as a trace marker of the PLGA nanoparticles and positively charged hydrophilic drug model, respectively. From the results of ex vivo accumulation test of this fluorescent nanoparticles, it was suggested that positively charged hydrophilic drugs reached the hair follicles as a nanoparticle, and then they were released from the nanoparticles.
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