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Biomacromolecules. 2018 Jul 9;19(7):2682-2690. doi: 10.1021/acs.biomac.8b00292. Epub 2018 Jun 8.

Cell-Penetrating Peptide-Patchy Deformable Polymeric Nanovehicles with Enhanced Cellular Uptake and Transdermal Delivery.

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Department of Bionano Technology , Hanyang University , Ansan 15588 , Republic of Korea.
Cosmetic Research Center, Coway Co. Ltd. , Seoul 08502 , Republic of Korea.
Department of Molecular & Life Sciences , Hanyang University , Ansan 15588 , Republic of Korea.
Department of Chemical and Molecular Engineering , Hanyang University , Ansan 15588 , Republic of Korea.
Center for Neuro-Medicine , Korea Institute of Science and Technology (KIST) , Seoul 02792 , Republic of Korea.
Department of Chemistry , Korea University , Seoul 02841 , Republic of Korea.
Department of Genetic Engineering , Kyung Hee University , Yongin 17104 , Republic of Korea.
Damy Chemical Co., Material Science Research Institute, Seoul 08501 , Republic of Korea.


We herein propose a polymeric nanovehicle system that has the ability to remarkably improve cellular uptake and transdermal delivery. Cell-penetrating peptide-patchy deformable polymeric nanovehicles were fabricated by tailored coassembly of amphiphilic poly(ethylene oxide)- block-poly(ε-caprolactone) (PEO- b-PCL), mannosylerythritol lipid (MEL), and YGRKKRRQRRR-cysteamine (TAT)-linked MEL. Using X-ray diffraction, differential scanning calorimetry, and nuclear magnetic resonance analyses, we revealed that the incorporation of MEL having an asymmetric alkyl chain configuration was responsible for the deformable phase property of the vehicles. We also discovered that the nanovehicles were mutually attracted, exhibiting a gel-like fluid characteristic due to the dipole-dipole interaction between the hydroxyl group of MEL and the methoxy group of PEO- b-PCL. Coassembly of TAT-linked MEL with the deformable nanovehicles significantly enhanced cellular uptake due to macropinocytosis and caveolae-/lipid raft-mediated endocytosis. Furthermore, the in vivo skin penetration test revealed that our TAT-patchy deformable nanovehicles remarkably improved transdermal delivery efficiency.

[Indexed for MEDLINE]

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