Cited by 28Nanoparticle-Based Drug DeliveryAdvanced Drug Delivery SystemsHydrogels: synthesis, properties, applications

Lipoyl Ester Terminated Star PLGA as a Simple and Smart Material for Controlled Drug Delivery Application

Wang, Xiuxiu, Cheng, Ru, Cheng, Liang, Zhong, Zhiyuan·2018·Biomacromolecules

Abstract

PLGA, a copolymer of lactide and glycolide, is one of the most used biodegradable polymers that find a wide range of biomedical applications including drug delivery and tissue engineering. However, in spite of remarkable advancement, nanotherapeutics based on PLGA might have drawbacks of inadequate stability, drug leakage, and slow drug release at the tumor site, which reduces its targeting ability and therapeutic efficacy. Here, we report that direct modification of star PLGA ends with lipoic acid, a natural antioxidant present in our human body, affords a smart material (sPLGA-LA) that forms reversibly crosslinked and bioresponsive multifunctional nanoparticles (sPLGA XNPs). Interestingly, sPLGA XNPs obtained in the presence of 23.0 wt % PEG-PDLLA displayed a small hydrodynamic size of 73 ± 1.2 nm, high stability against dilution and 10% serum, while fast destabilization under a reductive environment. Moreover, sPLGA XNPs achieved efficient loading of lipophilic anticancer drug model, doxorubicin (DOX), at a theoretical drug loading content of 13.3 wt %, giving DOX-loaded sPLGA XNPs with reduced drug leakage under physiological conditions as well as significantly accelerated drug release under 10 mM glutathione condition compared with both linear and star PLGA controls (denoted as lPLGA NPs and sPLGA NPs, respectively). Confocal microscopy and flow cytometry displayed obviously stronger DOX fluorescence in B16F10 melanoma cells treated with DOX-loaded sPLGA XNPs than with lPLGA and sPLGA counterparts. MTT assays revealed that DOX-sPLGA XNPs caused 2.4- and 4.2-fold higher antitumor activity toward B16F10 cells than DOX-sPLGA NPs and DOX-lPLGA NPs, respectively. Notably, in vivo pharmacokinetics studies showed prolonged circulation time and significantly improved AUC for DOX-sPLGA XNPs over lPLGA NPs control. Hence, lipoyl ester terminated star PLGA emerges as a simple and smart material for better-controlled anticancer drug delivery.

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Crossref · 10.1021/acs.biomac.8b00130

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  • An increase in polylactic acid content leads to less water absorption, thus reducing the rate of degradation.

    “The increase in polylactic acid content leads to less water absorption, thus reduces the rate of degradation.20”

    From Smart nanoparticles for cancer therapy (2023) · cites this paper as [20]

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Authors
Wang, X., Cheng, R., Cheng, L., & Zhong, Z.
Affiliations
Soochow University (CN)
Corresponding author
  • Cheng, Ru
  • Zhong, Zhiyuan
Venue
Biomacromolecules
Published
2018-03-19
Volume
19
Issue
4
Pages
1368-1373
ISSN
  • 1525-7797 (ISSN-L)
  • 1526-4602
OpenAlex
W2789619448
Cited by
28
References
48
Citations by year
2026: 3 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 3 · 2019: 6 · 2018: 4
FWCI
1.46
Type
journal article
Language
en
Open access
closed
Locations
  • Biomacromolecules (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (51373113, 51633005)
  • Priority Academic Program Development of Jiangsu Higher Education Institution
Topics
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
alpha-lipoic acid, smart nanoparticles, glutathione-responsive release, doxorubicin, controlled drug delivery, anticancer drug delivery, B16F10 melanoma cells, biodegradable polymers, nanoparticle stability, pharmacokinetics, tumor targeting
MeSH terms
Polylactic Acid-Polyglycolic Acid Copolymer, Antioxidants, Dioxanes, Doxorubicin, Flow Cytometry, Glutathione, Humans, Thioctic Acid, Neoplasms, Drug Delivery Systems, Nanoparticles, Biodegradable Plastics, Drug Liberation

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