Phospholipase A2-responsive antibiotic delivery via nanoparticle-stabilized liposomes for the treatment of bacterial infection
2014
Thamphiwatana, Soracha | Gao, Weiwei | Pornpattananangkul, Dissaya | Zhang, Qiangzhe | Fu, Victoria | Li, Jiayang | Li, Jieming | Obonyo, Marygorret | Zhang, Liangfang
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.
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