How Can We Exploit The Protein Corona?
Abstract
To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO), rhEPO was successfully formulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI , 0.3) and trace amount of protein aggregation.The zeta potential of the spherical micelles was in the range of -3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG-PLA micelles was about 80%.In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found.Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group.Increased hemoglobin concentrations were also found in the rat study.Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl.Therefore, PEG-PLA micelles can be a potential protein drug delivery system.
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The nanosized structure of micelles contributes to diffusion through leaky blood vessels to accumulate drugs in tumor tissues, known as the enhanced permeability and retention effect.
“The nanosized structure of micelles contributes to the diffusion of micelles through the leaky blood vessels to accumulate drugs in the tumor tissues, also known as enhanced permeability and retention (EPR) effect.40,41”
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- Authors
- Hamad-Schifferli, K.
- Affiliations
- Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Ave, Cambridge, MA02139, USA.
- Venue
- Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2012-12-20
- Volume
- 8
- Issue
- 1
- Pages
- 1-3
- ISSN
- 1743-5889 (ISSN-L)
- 1748-6963
- OpenAlex
- W2081746071
- Cited by
- 57
- References
- 21
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 8 · 2016: 6 · 2015: 6 · 2014: 9 · 2013: 8
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nanomedicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China (2010CB735602, 2012CB724003)
- 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 Biology › RNA Interference and Gene Delivery
- Keywords
- protein corona, recombinant human erythropoietin, polymeric micelles, protein drug delivery, pharmacokinetics, plasma protein binding, protein aggregation, encapsulation efficiency, hemoglobin, polydispersity index, zeta potential
- MeSH terms
- Proteins, Nanotechnology
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