Efficacy of intravenous amphotericin B-polybutylcyanoacrylate nanoparticles against cryptococcal meningitis in mice
Open accessAbstract
Amphotericin B deoxycholate (AmB), a classic antifungal drug, remains the initial treatment of choice for deep fungal infections, but it is not appropriate for treatment of cryptococcal meningitis due to its inability to pass through the blood-brain barrier (BBB). We examined the efficacy of amphotericin B-polybutylcyanoacrylate nanoparticles (AmB-PBCA-NPs) modified with polysorbate 80 that had a mean particle diameter less than 100 nanometers (69.0 ± 28.6 nm). AmB-PBCA-NPs were detected in the brain 30 minutes after systemic administration into BALB/c mice and had a higher concentration than systemically administered AmB liposome (AmB-L, P < 0.05); AmB was not detected in the brain. Following infection for 24 hours and then 7 days of treatment, the survival rate of mice in the AmB-PBCA-NP group (80%) was significantly higher than that of the AmB (0%) or AmB-L (60%) treatment groups. Fungal load was also lower when assessed by colony-forming unit counts obtained after plating infected brain tissue (P < 0.05). Our study indicates that AmB-PBCA-NPs with polysorbate 80 coating have the capacity to transport AmB across the BBB and is an efficient treatment against cryptococcal meningitis in a mouse model.
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AmB cannot be used clinically for the treatment of brain fungal infections due to its BBB impermeability.
“However, it cannot be used clinically for the treatment of brain fungal infections due to its BBB impermeability (25, 26).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [26]
The Introduction says BBB impermeability limits the clinical application of AmB against cryptococcal meningitis, supporting the stated reason. But the claim's absolute wording—“cannot be used clinically”—goes beyond the paper: the Discussion describes intrathecal injection as a clinical approach developed to overcome that limitation. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThis AmB concentration in the brain is higher than that which has previously been reported.
“Notably, this concentration of AmB is higher than that which has previously been reported (26).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [26]
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Ma, F., Yang, L., Sun, Z., Chen, J., Rui, X., Glass, Z., & Xu, Q. (2020) · Science Advances · doi:10.1126/sciadv.abb4429 · Cited by 218 · see citing works
- Authors
- Xu, Julin, G., Yuanjie, Z., Hai, W., Qiushi, R., & Jianghan, C.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Shanghai Changzheng Hospital (CN)
- Corresponding author
- Qiushi, Ren
- Jianghan, Chen
- Venue
- International Journal of Nanomedicine
- Publisher
- Informa UK Limited
- Published
- 2011-04
- Volume
- 6
- Pages
- 905
- ISSN
- 1176-9114 (ISSN-L)
- 1178-2013
- PMC
- PMC3124396
- OpenAlex
- W47211728
- Cited by
- 69
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 7 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 4 · 2014: 3 · 2013: 5 · 2012: 1
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Nanomedicine (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Key Research and Development Program of China (2011CB707504, 2010CB933903)
- Topics
- Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Keywords
- cryptococcal meningitis, amphotericin B, polybutylcyanoacrylate nanoparticles, blood-brain barrier, polysorbate 80 coating, liposomal amphotericin B, antifungal drug delivery, survival rate, fungal load, Cryptococcus neoformans
- MeSH terms
- Amphotericin B, Analysis of Variance, Animals, Antifungal Agents, Brain, Brain Chemistry, Cryptococcus neoformans, Enbucrilate, Injections, Intravenous, Mice, Inbred BALB C, Particle Size, Tissue Distribution, Survival Analysis, Drug Delivery Systems, Meningitis, Cryptococcal, Mice, Nanoparticles
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