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Hydrophilic drug-loaded PLGA nanoparticles for transdermal delivery

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Abstract

Transdermal delivery has been widely studied since it can avoid the effect of first-pass hepatic metabolism and deliver therapeutic agents as systemic or local administration for long period of time. In this study, procaine hydrochloride-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles for transdermal delivery were prepared using a combination of an antisolvent diffusion method with preferential solvation. The physicochemical characteristics and skin permeability were studied. Mean volume diameter of prepared nanoparticles was 99.4 ± 0.8 nm. They were “soft particles” and have negatively charged polyelectrolyte layer on the surface. Ex vivo experiment was carried out using the skin of male Sprague–Dawley rat with Franz diffusion cells. Compared to procaine hydrochloride free molecules, a higher amount of procaine hydrochloride was delivered through rat skin when procaine hydrochloride was loaded in nanoparticles. Moreover, a solution mixture of ethanol and isopropyl myristate, which were used as transdermal enhancers, improved skin permeability of the nanoparticles. In vivo experiment was carried out using male Sprague–Dawley rats aging 8 weeks. Samples were administered on rat abdominal skin (2.5 cm × 2.5 cm). After 9 h, drug concentrations of the skin and muscle under the area of sample administration were measured by using HPLC. Skin accumulation of the drug was increased when drug was included into PLGA nanoparticles, and muscle accumulation was increased by using transdermal enhancer. These results indicate that the nanoparticles that were prepared using a combination of an antisolvent diffusion method with preferential solvation were useful for transdermal delivery.

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Acknowledgements

This work was supported by the Program for Development of the Strategic Research Center in Private Universities, which is supported by MEXT (2010-2014).

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba, 278-8510, Japan

    Issei Takeuchi, Keishiro Tomoda, Megumi Koji & Kimiko Makino

  2. Center for Drug Delivery Research, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba, 278-8510, Japan

    Issei Takeuchi, Keishiro Tomoda & Kimiko Makino

  3. Center for Physical Pharmaceutics, Tokyo University of Science, 2641, Yamazaki, Noda, Chiba, 278-8510, Japan

    Issei Takeuchi, Keishiro Tomoda & Kimiko Makino

Authors
  1. Issei Takeuchi
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  2. Keishiro Tomoda
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  3. Megumi Koji
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  4. Kimiko Makino
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Correspondence to Kimiko Makino.

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Animal care was conducted under the Guidelines for Animal Experimentation of Tokyo University of Science, which are based on the Guidelines for Animal Experimentation of the Japanese Association for Laboratory Animal Science.

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The authors declare that they have no conflict of interest.

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Takeuchi, I., Tomoda, K., Koji, M. et al. Hydrophilic drug-loaded PLGA nanoparticles for transdermal delivery. Colloid Polym Sci 295, 977–983 (2017). https://doi.org/10.1007/s00396-017-4087-8

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  • DOI: https://doi.org/10.1007/s00396-017-4087-8

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