Pharmaceutical differences between block copolymer self-assembled and cross-linked nanoassemblies as carriers for tunable drug release

Hyun Jin Lee, Younsoo Bae

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Purpose: To identify the effects of cross-linkers and drug-binding linkers on physicochemical and biological properties of polymer nanoassembly drug carriers. Methods: Four types of polymer nanoassemblies were synthesized from poly(ethylene glycol)-poly(aspartate) [PEG-p(Asp)] block copolymers: self-assembled nanoassemblies (SNAs) and cross-linked nanoassemblies (CNAs) to each of which an anticancer drug doxorubicin (DOX) was loaded by either physical entrapment or chemical conjugation (through acid-sensitive hydrazone linkers). Results: Drug loading in nanoassemblies was 27 ~ 56% by weight. The particle size of SNA changed after drug and drug-binding linker entrapment (20 ~ 100 nm), whereas CNAs remained 30 ~ 40 nm. Drug release rates were fine-tunable by using amide cross-linkers and hydrazone drug-binding linkers in combination. In vitro cytotoxicity assays using a human lung cancer A549 cell line revealed that DOX-loaded nanoassemblies were equally potent as free DOX with a wide range of drug release half-life (t1/2 = 3.24 ~ 18.48 h, at pH 5.0), but 5 times less effective when t1/2 = 44.52 h. Conclusion: Nanoassemblies that incorporate cross-linkers and drug-binding linkers in combination have pharmaceutical advantages such as uniform particle size, physicochemical stability, fine-tunable drug release rates, and maximum cytotoxicity of entrapped drug payloads.

Original languageEnglish
Pages (from-to)478-488
Number of pages11
JournalPharmaceutical Research
Issue number2
StatePublished - Feb 2013

Bibliographical note

Funding Information:
This research is supported by the Kentucky Lung Cancer Research Program. Authors thank Alli Eckman for assisting cytotoxicity assays.


  • cross-linked nanoassemblies
  • drug carriers
  • drug delivery
  • nanoparticles
  • polymer micelles

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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