# Development and evaluation of a self-assembled nanoparticle-based prodrug for sustained delivery of 4-phenylbutyric acid

https://mdr.nims.go.jp/datasets/788e6acf-b3ff-46c4-a5cb-10a659eeeb51

## File

- [Development and evaluation of a self-assembled nanoparticle-based prodrug for sustained delivery of 4-phenylbutyric acid.pdf](https://mdr.nims.go.jp/filesets/ff404819-c59b-45dd-baff-76cf13cb6217/download) ([Detail](https://mdr.nims.go.jp/filesets/ff404819-c59b-45dd-baff-76cf13cb6217.md))

## Id

788e6acf-b3ff-46c4-a5cb-10a659eeeb51

## Local identifier



## Visibility

open_to_public

## State

published

## Created at

2025-03-25T06:25:06.724156Z

## Updated at

2025-07-16T07:17:05.754645Z

## Published at

2025-04-02T09:09:44.323415Z

## Doi

https://doi.org/10.48505/nims.5383

## First published url

https://doi.org/10.1080/14686996.2025.2482512

## Date published

2025-12-31

## Recorded date published

2025-12-31

## Resource type

journal_article

## Manuscript type

accepted_manuscript

## Collection



## Title

- title: Development and evaluation of a self-assembled nanoparticle-based prodrug
    for sustained delivery of 4-phenylbutyric acid
  title_type: original
  lang: en

## Description

- description: 4-Phenylbutyric acid (PBA) is a small molecule with promising therapeutic
    potential for treating various diseases, including cancer and neurodegenerative
    disorders, due to its dual ability to reduce endoplasmic reticulum stress and
    inhibit histone deacetylases. However, its clinical application is hindered by
    rapid clearance from the body, necessitating frequent dosing that increases the
    risk of adverse effects. To address these limitations, we developed a nanoparticle-based
    prodrug (NanoPBA) utilizing the amphiphilic block copolymer poly(ethylene glycol)-b-poly(vinyl
    4-phenylbutyrate) [PEG-b-P(VPBA)]. This system self-assembles into micelles, enabling
    controlled and sustained PBA delivery. The synthesis and characterization of NanoPBA
    revealed its high stability under physiological conditions and enzyme-responsive
    PBA release. NanoPBA demonstrated a controlled release profile in vitro, reducing
    burst release while maintaining therapeutic efficacy. Cytotoxicity assays using
    normal cell lines, including endothelial cells (BAEC), macrophages (RAW264.7),
    and rat gastric cells (RGM-1), showed minimal cytotoxic effects compared to the
    parent low-molecular-weight PBA. Furthermore, in vivo studies conducted in healthy
    C57/BL6J mice confirmed NanoPBA’s biocompatibility, with no significant adverse
    effects observed at therapeutic doses ranging from 200 to 500 mg-PBA/kg via oral
    administration. In conclusion, NanoPBA offers a controlled release profile, enhanced
    biocompatibility, and reduced toxicity, addressing the limitations associated
    with conventional PBA administration. These attributes make NanoPBA a promising
    candidate for improving the therapeutic efficacy and safety of PBA in clinical
    applications, particularly in diseases where maintaining consistent drug levels
    is crucial for treatment outcomes.
  description_type: abstract
  lang: en

## Creator

- name: Kikka Maeda
  role: author
  organization: Graduate School of Pure an Applied Sciences, University of Tsukuba,
  department: Department of Materials Science
- name: Babita Shashni
  role: author
  organization: Department of Materials Science, Graduate School of Pure an Applied
    Sciences, University of Tsukuba
  department: Organization for Research and Development of Innovative Science and
    Technology, Kansai University
- name: Hirofumi Matsui
  role: author
  organization: University of Tsukuba,
  department: Division of Gastroenterology, Faculty of Medicine
- name: Yukio Nagasaki
  role: author
  organization: Graduate School of Pure an Applied Sciences, University of Tsukuba
  department: Department of Materials Science

## Contact agent



## Publisher

organization: Taylor & Francis

## Managing organization



## Keyword

- subject: Endoplasmic reticulum stress modulation
  schema: not_defined
- subject: Chemical chaperone
  schema: not_defined
- subject: Prodrug of short chain fatty acid
  schema: not_defined
- subject: 4-Phenylbutyric acid
  schema: not_defined
- subject: Sustained drug release
  schema: not_defined
- subject: Amphiphilic block copolymer micelle
  schema: not_defined

## Rights

- identifier: https://creativecommons.org/licenses/by-nc/4.0/

## Other identifier(s)



## Data origin

- data_origin_type: other

## Embargo



## Journal

- title: Science and Technology of Advanced Materials
  issn: '14686996'
  volume: '26'
  article_number: '2482512'

## Conference



## Related item



## Funding



## Instrument



## Instrument operator



## Instrument managing organization



## Measurement method



## Specimen



## Chemical composition



## Structure for specimen



## Structural feature for specimen



## Specific property for specimen



## Process for specimen treatment



## Computational method



## Energy level/transition state



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## Custom property



## Fileset

- id: ff404819-c59b-45dd-baff-76cf13cb6217
  filename: Development and evaluation of a self-assembled nanoparticle-based prodrug
    for sustained delivery of 4-phenylbutyric acid.pdf
  content_type: application/pdf
  size: 5575955
  md5: acff28a73949fee23bcf14b1bc526b4d

## Thumbnail

fileset_id: ff404819-c59b-45dd-baff-76cf13cb6217
filename: Development and evaluation of a self-assembled nanoparticle-based prodrug
  for sustained delivery of 4-phenylbutyric acid.pdf