Fabrication of electroactive polypyrrole-tungsten disulfide nanocomposite for enhanced in vivo drug release in mice skin

Pa Fan Hsiao; Rajeshkumar Anbazhagan; Hsieh-Chih Tsai; Rajakumari Krishnamoorthi; Sheng-Jiun Lin; Shuian-Yin Lin; Kuei-Yi Lee; Chen-Yu Kao; Ruei-San Chen; Juin-Yih Lai

doi:10.1016/j.msec.2019.110330

Fabrication of electroactive polypyrrole-tungsten disulfide nanocomposite for enhanced in vivo drug release in mice skin

Mater Sci Eng C Mater Biol Appl. 2020 Feb:107:110330. doi: 10.1016/j.msec.2019.110330. Epub 2019 Oct 23.

Authors

Affiliations

¹ Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Medicine, Nursing and Management College, Taipei, Taiwan; Mackay Medical College, New Taipei City, Taiwan.
² Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan; Advanced Membrane Materials Research Center, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
³ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan; Advanced Membrane Materials Research Center, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan. Electronic address: h.c.tsai@mail.ntust.edu.tw.
⁴ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan.
⁵ Industrial Technology Research Institute, Hsinchu, Taiwan.
⁶ Graduate Institute of Electro-Optical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan; Department of Electronic and Computer Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
⁷ Deaprtment of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.
⁸ Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan; Advanced Membrane Materials Research Center, Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei, Taiwan; R&D Center for Membrane Technology and Department of Chemical Engineering, Chung Yuan University, Chung-Li, Taiwan.

PMID: 31761209
DOI: 10.1016/j.msec.2019.110330

Abstract

The present study focused on the development of electric stimuli drug release carrier based on transition metal dicgalcogenides. First, tungsten disulfide (WS₂) was exfoliated and functionalized using thiol chemistry with various thiol-terminated ligands such as thioglycolic acid (TGA), mercaptosuccinic acid (MSA), and 2-ethanethiol (2ET). The exfoliated WS₂ underwent non-covalent coating with an electrically conductive polypyrrole (PPy) for functionalization, of which MSA-WS₂-PPy achieved the highest 5-FU (anticancer drug) loading. An electrically-stimulated drug release experiment showed that TGA-WS₂-PPy achieved a higher drug release (90%) than MSA-WS₂-PPy (70%) and 2ET-WS₂-Ppy (35%). The TGA-WS₂-PPy exhibited swelling/recombination between PPY and MSA-WS₂ substrate under electrical stimulation, resulting in the highest 5-FU release. From the MTT assay result, there was no significant toxicity observed for TGA-WS₂-PPy-FU on HaCaT cells, indicating the biocompatibility of TGA-WS₂-PPy-FU in the absence of electrical stimulation. However, HaCaT cells died when incubated with TGA-WS₂-PPy-FU under electrical stimulation. Finally, Raman mapping studies for TGA-WS₂-PPy drug release in the skin of nude mice demonstrated that the carrier penetrated deeper into the skin of the mice while other systems failed to exhibit significant effects under electrical stimulation. The present study offers a novel approach in developing a non-invasive electrically-stimulated drug release system based on WS₂ and an externally-controlled delivery model.

Keywords: Conducting polymer; Electrical property; Exfoliation; In vivo drug release; Polypyrrole (PPy); Tungsten disulfide (WS(2)).

MeSH terms

Administration, Cutaneous
Animals
Antimetabolites, Antineoplastic / administration & dosage
Antimetabolites, Antineoplastic / pharmacokinetics
Cell Line
Disulfides / chemistry
Drug Carriers / administration & dosage
Drug Carriers / chemistry
Drug Carriers / pharmacokinetics
Drug Delivery Systems / methods*
Drug Liberation
Electric Stimulation
Female
Fluorouracil / administration & dosage
Fluorouracil / pharmacokinetics
Humans
Keratinocytes / drug effects
Mice, Inbred ICR
Mice, Nude
Nanocomposites / administration & dosage
Nanocomposites / chemistry*
Polymers / chemistry*
Pyrroles / chemistry*
Skin / drug effects*
Spectrum Analysis, Raman
Tungsten Compounds / chemistry*

Substances

Antimetabolites, Antineoplastic
Disulfides
Drug Carriers
Polymers
Pyrroles
Tungsten Compounds
polypyrrole
Fluorouracil