Lipid-polymer hybrid nanoparticles with rhamnolipid-triggered release capabilities as anti-biofilm drug delivery vehicles  

作　　者：Wean Sin Cheow Kunn Hadinoto 

机构地区：[1]School of Chemical and Biomedical Engineering, Nanyang Technological University

出　　处：《Particuology》2012年第3期327-333,共7页颗粒学报（英文版）

基　　金：the Ministry of Education of Singapore AcRF Tier 1 Grant No. RG 76/10 for financial support

摘　　要：In lung biofilm infection therapies, the use of lipid-polymer hybrid nanoparticles to encapsulate drugs has emerged as a promising alternative to using liposomes because they have superior physicochemical stability and still possess the biofilm affinity and sputum-penetrating ability ofliposomes. To be deemed equally efficacious as liposomes against bacterial biofilms, however, the capability of hybrid nanoparticles to target-release encapsulated drugs at biofilm colonies must be demonstrated. This communication details our investigations into the trigger-release characteristics of hybrid nanoparticles in response to encountering rhamnolipids, which are ubiquitously present in biofilm colonies of Pseudomonas aeruginosa, a major respiratory pathogen. Poly（lactic-co-glycolic acid） and phospbatidylcholine were used as the poly- mer nanoparticle core and lipid coat, respectively. These investigations were performed using compounds from various biopharmaceutical classification systems （BCS） that differ in their lipid-membrane permeabilities. The release of BCS Class II1 compounds, which have poor lipid-membrane permeabilities, was successfully triggered by rhamnolipids at a concentration approximately equal to their clinically observed value, and this release was attributed to the disruption of lipid coats by rhamnolipid micelles. Not unexpectedly, BCS Class I compounds, which have high lipid-membrane permeabilities, were released freely whether or not rhamnolipids were present. The rate of the triggered release can be controlled by incor- porating an additional lipid layer on the hybrid nanoparticles via the electrostatically driven adsorption of lipid vesicles.In lung biofilm infection therapies, the use of lipid-polymer hybrid nanoparticles to encapsulate drugs has emerged as a promising alternative to using liposomes because they have superior physicochemical stability and still possess the biofilm affinity and sputum-penetrating ability ofliposomes. To be deemed equally efficacious as liposomes against bacterial biofilms, however, the capability of hybrid nanoparticles to target-release encapsulated drugs at biofilm colonies must be demonstrated. This communication details our investigations into the trigger-release characteristics of hybrid nanoparticles in response to encountering rhamnolipids, which are ubiquitously present in biofilm colonies of Pseudomonas aeruginosa, a major respiratory pathogen. Poly（lactic-co-glycolic acid） and phospbatidylcholine were used as the poly- mer nanoparticle core and lipid coat, respectively. These investigations were performed using compounds from various biopharmaceutical classification systems （BCS） that differ in their lipid-membrane permeabilities. The release of BCS Class II1 compounds, which have poor lipid-membrane permeabilities, was successfully triggered by rhamnolipids at a concentration approximately equal to their clinically observed value, and this release was attributed to the disruption of lipid coats by rhamnolipid micelles. Not unexpectedly, BCS Class I compounds, which have high lipid-membrane permeabilities, were released freely whether or not rhamnolipids were present. The rate of the triggered release can be controlled by incor- porating an additional lipid layer on the hybrid nanoparticles via the electrostatically driven adsorption of lipid vesicles.

关 键 词：Hybrid nanoparticlesLiposomesBiofilmPseudomonas aeruginosaTriggered releaseRhamnolipidCalcein 

分 类 号：R943[医药卫生—药剂学]