Layer-by-layer assembly of liposomal nanoparticles with PEGylated polyelectrolytes enhances systemic delivery of multiple anticancer drugs

Thiruganesh Ramasamy, Ziyad S. Haidar, Tuan Hiep Tran, Ju Yeon Choi, Jee Heon Jeong, Beom Soo Shin, Han Gon Choi, Chul Soon Yong, Jong Oh Kim

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Layer-by-layer (LbL)-engineered nanoparticles (NPs) are a promising group of therapeutic carriers used in an increasing number of biomedical applications. The present study uses a controlled LbL process to create a multidrug-loaded nanoplatform capable of promoting blood circulation time, biodistribution profile and controlling drug release in the dynamic systemic environment. LbL assembly is achieved by sequential deposition of poly-L-lysine (PLL) and poly(ethylene glycol)-block-poly(L-aspartic acid) (PEG-b-PLD) on liposomal nanoparticles (LbL-LNPs). This generates spherical and stable multilayered NPs ∼240 nm in size, enabling effective systemic administration. The numerous functional groups and compartments in the polyelectrolyte shell and core facilitate loading with doxorubicin and mitoxantrone. The nanoarchitecture effectively controls burst release, providing different release kinetics for each drug. LbL-LNPs are pH-sensitive, indicating that intracellular drug release can be increased by the acidic milieu of cancer cells. We further demonstrate that the LbL nanoarchitecture significantly reduces the elimination rates of both drugs tested and markedly extends their systemic circulation times, paving the way for efficacious tumor drug delivery. Because this delivery system accommodates multiple drugs, improves drug half-life and diminishes burst release, it provides an exciting platform with remarkable potential for combination therapeutics in cancer therapy.

Original languageEnglish
Pages (from-to)5116-5127
Number of pages12
JournalActa Biomaterialia
Volume10
Issue number12
DOIs
StatePublished - 2014
Externally publishedYes

Bibliographical note

Funding Information:
This research was supported by a National Research Foundation of Korea ( NRF ) grant funded by the Ministry of Education, Science and Technology (No. 2012R1A2A2A02044997 and No. 2012R1A1A1039059 ).

Publisher Copyright:
© 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keywords

  • Doxorubicin
  • Layer-by-layer
  • Liposome
  • Mitoxantrone
  • Nanoarchitecture

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