A facile and efficient approach for the production of reversible disulfide cross-linked micelles

Yuanpei Li, Gaurav Bharadwaj, Joyce S Lee

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Nanomedicine is an emerging form of therapy that harnesses the unique properties of particles that are nanometers in scale for biomedical application. Improving drug delivery to maximize therapeutic outcomes and to reduce drug-associated side effects are some of the cornerstones of present-day nanomedicine. Nanoparticles in particular have found a wide application in cancer treatment. Nanoparticles that offer a high degree of flexibility in design, application, and production based on the tumor microenvironment are projected to be more effective with rapid translation into clinical practice. The polymeric micellar nano-carrier is a popular choice for drug delivery applications. In this article, we describe a simple and effective protocol for synthesizing drug-loaded, disulfide cross-linked micelles based on the self-assembly of a well-defined amphiphilic linear-dendritic copolymer (telodendrimer, TD). TD is composed of polyethylene glycol (PEG) as the hydrophilic segment and a thiolated cholic acid cluster as the core-forming hydrophobic moiety attached stepwise to an amine-terminated PEG using solution-based peptide chemistry. Chemotherapy drugs, such as paclitaxel (PTX), can be loaded using a standard solvent evaporation method. The O2-mediated oxidation was previously utilized to form intra-micellar disulfide cross-links from free thiol groups on the TDs. However, the reaction was slow and not feasible for large-scale production. Recently, an H2O2-mediated oxidation method was explored as a more feasible and efficient approach, and it was 96 times faster than the previously reported method. Using this approach, 50 g of PTX-loaded, disulfide cross-linked nanoparticles have been successfully produced with narrow particle size distribution and high drug loading efficiency. The stability of the resulting micelle solution is analyzed using disrupting conditions such as co-incubation with a detergent, sodium dodecyl sulfate, with or without a reducing agent. The drug-loaded, disulfide cross-linked micelles demonstrated less hemolytic activity when compared to their non-cross-linked counterparts.

Original languageEnglish (US)
Article numbere54722
JournalJournal of Visualized Experiments
Volume2016
Issue number118
DOIs
StatePublished - Dec 23 2016

Fingerprint

Micelles
Disulfides
Medical nanotechnology
Nanoparticles
Drug delivery
Pharmaceutical Preparations
Nanomedicine
Polyethylene glycols
Paclitaxel
Oxidation
Oncology
Chemotherapy
Detergents
Sodium dodecyl sulfate
Reducing agents
Cholic Acid
Particle size analysis
Self assembly
Peptides
Reducing Agents

Keywords

  • Biochemistry
  • Disulfide cross-linking
  • Drug delivery
  • Hydrogen peroxide-mediated oxidation
  • Issue 118
  • Micelles
  • Nanoparticle
  • Telodendrimer

ASJC Scopus subject areas

  • Neuroscience(all)
  • Chemical Engineering(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A facile and efficient approach for the production of reversible disulfide cross-linked micelles. / Li, Yuanpei; Bharadwaj, Gaurav; Lee, Joyce S.

In: Journal of Visualized Experiments, Vol. 2016, No. 118, e54722, 23.12.2016.

Research output: Contribution to journalArticle

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