Therapeutic Efficiency Of Intravenous Amphoteric B-nanoparticles Against Experimental Cryptococcal Meningitis

[Background] Recently, there has been a dramatic rise in the incidence of cryptococcal meningitis. As a widely used, classic antifungal agent, amphotericin B (AmB) shows some discrepancy in the treatment of cryptococcal meningitis, most of which is its inability to cross the blood-brain barrier (BBB). Nanoparticles are demonstrated to be a good vector for drug-brain-targeting system.[Objective] To prepare AmB-polybutylcyanoacrylate nanoparticles (AmB-PBCA-NP) and Amb-poly lactic acid/polyethylene glycol nanoparticles (AmB-PLA/PEG-NP) with proper surface modification, which meet the request for brain targeting. [Method] Prepare AmB-PBCA-NP and AmB-PLA/PEG-NP and Characteristics such as particle diameter, encapsulation ratio were measured; Study the pharmacokinetics of different formula of AmB in mice; Establish the cryptococcal meningitis model in BALB/c mice; Observe the survival rate and CFU in brain; The toxicity of different preparations was also evaluated. [Result] AmB-PBCA-NP and AmB-PLA/PEG-NP were successfully prepared with polysorbate 80 (T-80) coated as surface modification. Both of two nano-drugs showed superior concentration in brain tissue to AmB-Doc and AmB-L. The survival rate of mice with cryptococcal meningitis treated by nano-drugs was significantly increased. The CFU per gram of brain showed notable downtrend. AmB...