title: Nano-antibiotics in chronic lung infection therapy against Pseudomonas aeruginosa.
abstract: Antibiotic encapsulation into nanoparticle carriers has emerged as a promising inhaled antibiotic formulation for treatment of chronic Pseudomonas aeruginosa lung infection prevalent in chronic obstructive pulmonary diseases. Attributed to their prolonged lung retention, sustained antibiotic release, and mucus penetrating ability, antibiotic nanoparticles, or nano-antibiotics in short, can address the principal weakness of inhaled antibiotic solution, i.e. low antibiotic exposure in the vicinity of P. aeruginosa biofilm colonies resulting in diminished anti-pseudomonal efficacy after repeated uses. This review details the current state of development and limitations of the two most widely studied forms of nano-antibiotics, i.e. liposomes and polymer nanoparticles. Factors in their formulation that influence the anti-pseudomonal efficacy in vitro and in vivo, such as liposome's membrane rigidity, surface charge, size, and polymer hydrophobicity, are discussed. This review reveals that the superior anti-pseudomonal efficacy of liposomal antibiotics to free antibiotics has been clearly established when they are correctly formulated, with several liposomal antibiotic formulations are currently undergoing clinical trials. Liposomal antibiotics, nevertheless, are not without limitation due to their weak physicochemical stability. In contrast, only mucus penetrating ability of the more stable polymeric nano-antibiotics has been established, while their anti-pseudomonal efficacy has only been examined in vitro from which their superiority to free antibiotics has not been ascertained. Lastly, future research needs to bring liposome and polymer-based nano-antibiotics closer to their clinical realization are identified.
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore. Electronic address: kunnong@ntu.edu.sg.
authors.forename: Kunn
authors.initials: K
authors.lastname: Hadinoto
authors.affiliation: School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459, Singapore.
authors.forename: Wean Sin
authors.initials: WS
authors.lastname: Cheow
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D053758:Nanoparticles / Q000737:chemistry*; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents
keywords: Cystic fibrosis; Drug nanoparticles; Liposomes; Mucus barrier; Pulmonary biofilm