Long-circulating sterically stabilized liposomes in the treatment of infections.
The administration of antimicrobial agents encapsulated in long-circulating sterically stabilized liposomes results in a considerable enhancement of therapeutic efficacy compared with the agents in the free form. After liposomal encapsulation, the pharmacokinetics of the antimicrobial agents is significantly changed. An increase in circulation time and reduction in toxic side effects of the agents are observed. In contrast to other types of long-circulating liposomes, an important characteristic of these sterically stabilized liposomes is that their prolonged blood circulation time is, to a high degree, independent of liposome characteristics such as liposome particle size, charge and lipid composition (rigidity) of the bilayer, and lipid dose. This provides the opportunity to manipulate antibiotic release from these liposomes at the site of infection, which is important in view of the differences in pharmacodynamics of different antibiotics and can be done without compromising blood circulation time and degree of target localization of these liposomes. Depending on the liposome characteristics and the agent encapsulated, antibiotic delivery to the infected site is achieved, or the liposomes act as a micro-reservoir function for the antibiotic. In experimental models of localized or disseminated bacterial and fungal infections, the sterically stabilized liposomes have successfully been used to improve antibiotic treatment using representative agents of various classes of antibacterial agents such as the beta-lactams, the aminoglycosides, and the quinolones or the antifungal agent amphotericin B. Extensive biodistribution studies have been performed. Critical factors that contribute to liposome target localization in infected tissue have been elucidated. Liposome-related factors that were investigated were poly(ethylene glycol) density, particle size, bilayer fluidity, negative surface charge, and circulation kinetics. Host-related factors focused on the components of the inflammatory response.
Bakker-Woudenberg
Irma A J M
IA
Department of Medical Microbiology and Infectious Diseases, Erasmus University Rotterdam, Rotterdam, The Netherlands.
Schiffelers
Raymond M
RM
Storm
Gert
G
Becker
Martin J
MJ
Guo
Luke
L
D000645:Ammonium Sulfate / Q000737:chemistry; D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use*; D002442:Ceftazidime / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004337:Drug Carriers; D005839:Gentamicins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D007239:Infections / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry; D015394:Molecular Structure; D011014:Pneumonia / Q000188:drug therapy / Q000382:microbiology; D051381:Rats; D012995:Solubility
D000890:Anti-Infective Agents; D004337:Drug Carriers; D005839:Gentamicins; D008081:Liposomes; D002939:Ciprofloxacin; D000666:Amphotericin B; D002442:Ceftazidime; D000645:Ammonium Sulfate