Issue 46, 2014

Phospholipase A2-responsive antibiotic delivery via nanoparticle-stabilized liposomes for the treatment of bacterial infection

Abstract

Adsorbing small charged nanoparticles onto liposome surfaces to stabilize them against fusion and payload leakage has resulted in a new class of liposomes capable of environment-responsive drug delivery. Herein, we engineered a liposome formulation with a lipid composition sensitive to bacterium-secreted phospholipase A2 (PLA2) and adsorbed chitosan-modified gold nanoparticles (AuChi) onto the liposome surface. The resulting AuChi-stabilized liposomes (AuChi-liposomes) showed prohibited fusion activity and negligible drug leakage. However, upon exposure to either purified PLA2 enzyme or PLA2 secreted by Helicobacter pylori (H. pylori) bacteria in culture, AuChi-liposomes rapidly released the encapsulated payloads and such responsive release was retarded by adding quinacrine dihydrochloride, a PLA2 inhibitor. When loaded with doxycycline, AuChi-liposomes effectively inhibited H. pylori growth. Overall, the AuChi-liposomes allowed for smart “on-demand” antibiotic delivery: the more enzymes or bacteria present at the infection site, the more drugs will be released to treat the infection. Given the strong association of PLA2 with a diverse range of diseases, the present liposomal delivery technique holds broad application potential for tissue microenvironment-responsive drug delivery.

Graphical abstract: Phospholipase A2-responsive antibiotic delivery via nanoparticle-stabilized liposomes for the treatment of bacterial infection

Article information

Article type
Paper
Submitted
08 Jul 2014
Accepted
03 Sep 2014
First published
04 Sep 2014

J. Mater. Chem. B, 2014,2, 8201-8207

Phospholipase A2-responsive antibiotic delivery via nanoparticle-stabilized liposomes for the treatment of bacterial infection

S. Thamphiwatana, W. Gao, D. Pornpattananangkul, Q. Zhang, V. Fu, J. Li, J. Li, M. Obonyo and L. Zhang, J. Mater. Chem. B, 2014, 2, 8201 DOI: 10.1039/C4TB01110D

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