In Vitro and In Vivo Study of Amphotericin B Formulation with Quaternized Bioreducible Lipidoids
Abstract
Invasive fungal infections are well-known causes of morbidity and mortality in immunocompromised patients. Amphotericin B (AmB) is a polyene fungicidal agent with excellent properties of the broad antifungal spectrum, high activity, and relatively rare drug resistance. However, significant toxicities limit the clinical application of AmB and its conventional formulation AmB deoxycholate (Fungizone). Here we investigated nanoparticle formulations of AmB using synthetic biodegradable lipidoids and evaluated their stability, in vitro antifungal efficacy, and in vivo toxicity and pharmacokinetics. We found that the AmB formulated using a mixture of quaternized lipidoid (Q78-O14B) and DSPE-PEG2000 has the size around 70-100 nm and is stable during storage. The formulation showed no hemotoxicity to red blood cells (RBCs) in vitro . It also possesses the highest antifungal activity ( in vitro ) and lowest toxicity (both in vitro and in vivo ). These metrics are significantly superior to the commercial antifungal product Fungizone. Meanwhile, AmB/Q78-O14B-P exhibited prolonged blood circulation in comparison to Fungizone in vivo. In AmB/Q78-O14B-P formulation, AmB was still detectable in the liver, spleen, and lung tissues with a concentration above the minimum inhibitory concentrations 72 h after low-dose intravenous injection. Based on these results, AmB in lipidoid nanoparticle formulation may produce sustained antifungal activity against blood-borne and systemic organ infections.…
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In a previous study, none of the authors' synthetic lipidoid nanoparticles were capable of permeating the BBB to deliver AmB into the mouse brain.
“Recently, we formulated AmB in synthetic lipidoid nanoparticles and conducted a thorough pharmacokinetics (PK) and biodistribution study of the AmB formulations using traditional synthetic LNPs, but in that study, none of our LNPs were capable of permeating the BBB to deliver AmB into the mouse brain (27).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [27]
In a previous report, quaternized lipidoids provided stable AmB formulations with smaller particle size compared with nonquaternized lipids.
“In the previous report, we found that the quaternized lipidoids provided stable AmB formulation with smaller particle size, comparing with the nonquaternized lipids (27).”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [27]
In a previous report, AmB was undetectable in the brain after systemic delivery with traditional synthetic lipidoids.
“Notably, in our previous report, AmB was undetectable in the brain after systemic delivery with traditional synthetic lipidoids, indicating that the NT1-lipidoid formulations enhanced the AmB delivery into the mouse brain.”
From Neurotransmitter-derived lipidoids (NT-lipidoids) for enhanced brain delivery through intravenous injection (2020) · cites this paper as [27]
Cites
Recent advances with liposomes as pharmaceutical carriers
Torchilin, V. P. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1632 · Cited by 5,282 · see citing works
PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel
Zhang, Y., Huo, M., Zhou, J., & Xie, S. (2010) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2010.01.007 · Cited by 2,073 · see citing works
A combinatorial library of lipid-like materials for delivery of RNAi therapeutics
Akinc, A., Zumbuehl, A., Goldberg, M. S., Leshchiner, E. S., Busini, V., Hossain, N., Bacallado, S., Nguyen, D. N., Fuller, J. E., Alvarez, R., et al. (2008) · Nature Biotechnology · doi:10.1038/nbt1402 · Cited by 1,228 · see citing works
Lipid-like materials for low-dose, in vivo gene silencing
Love, K. T., Mahon, K. P., Levins, C. G., Whitehead, K. A., Querbes, W., Dorkin, J. R., Qin, J., Cantley, W., Qin, L. L., Racie, T., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910603106 · Cited by 969 · see citing works
Amphotericin B formulations: a comparative review of efficacy and toxicity
Hamill, R. J. (2013) · Drugs · doi:10.1007/s40265-013-0069-4 · Cited by 807 · see citing works
Efficient delivery of genome-editing proteins using bioreducible lipid nanoparticles
Wang, M., Zuris, J. A., Meng, F., Rees, H., Sun, S., Deng, P., Han, Y., Gao, X., Pouli, D., Wu, Q., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1520244113 · Cited by 624 · see citing works
Self-citationAntifungal Drug Development: Challenges, Unmet Clinical Needs, and New Approaches
Roemer, T., & Krysan, D. J. (2014) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a019703 · Cited by 593 · see citing works
Stone, N. R. H., Bicanic, T., Salim, R., & Hope, W. (2016) · Drugs · doi:10.1007/s40265-016-0538-7 · Cited by 537 · see citing works
Antifungal drug resistance among <i>Candida</i> species: mechanisms and clinical impact
Sanguinetti, M., Posteraro, B., & Lass‐Flörl, C. (2015) · Mycoses · doi:10.1111/myc.12330 · Cited by 394 · see citing works
Ishida, T., Harashima, H., & Kiwada, H. (2002) · Bioscience Reports · doi:10.1023/a:1020134521778 · Cited by 329 · see citing works
Amphotericin B Formulations and Drug Targeting
Torrado, J. J., Espada, R., Ballesteros, M. P., & Torrado, S. (2007) · Journal of Pharmaceutical Sciences · doi:10.1002/jps.21179 · Cited by 301 · see citing works
Overview of the lipid formulations of amphotericin B
Dupont, B. (2002) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/49.suppl_1.31 · Cited by 261 · see citing works
Shao, K., Huang, R., Li, J., Han, L., Ye, L., Lou, J., & Jiang, C. (2010) · Journal of Controlled Release · doi:10.1016/j.jconrel.2010.06.018 · Cited by 189 · see citing works
Effect of aggregation state on the toxicity of different amphotericin B preparations
Espada, R., Valdespina, S., Alfonso, C., Rivas, G., Ballesteros, M. P., & Torrado, J. J. (2008) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2008.05.013 · Cited by 119 · see citing works
Amphotericin B-entrapping lipid nanoparticles and their in vitro and in vivo characteristics
Jung, S. H., Lim, D. H., Jung, S. H., Lee, J. E., Jeong, K.-S., Seong, H., & Shin, B. C. (2009) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2009.02.021 · Cited by 113 · see citing works
Radwan, M. A., AlQuadeib, B. T., Šiller, L., Wright, M. C., & Horrocks, B. R. (2017) · Drug Delivery · doi:10.1080/10717544.2016.1228715 · Cited by 103 · see citing works
Li, Y., Yang, T., Yu, Y., Shi, N., Yang, L., Glass, Z., Bolinger, J., Finkel, I. J., Li, W., & Xu, Q. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.03.011 · Cited by 84 · see citing works
Self-citationHemolytic and pharmacokinetic studies of liposomal and particulate amphotericin B formulations
Serrano, D. R., Hernández, L., Fleire, L., González-Alvarez, I., Montoya, A., Ballesteros, M. P., Dea‐Ayuela, M. A., Miró, G., Bolás-Fernández, F., & Torrado, J. J. (2013) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2013.02.038 · Cited by 84 · see citing works
Swenson, C. E., Perkins, W. R., Roberts, P., Ahmad, I., Stevens, R., Stevens, D. A., & Janoff, A. S. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.4.767 · Cited by 82 · see citing works
Fernández-García, R., de Pablo, E., Ballesteros, M. P., & Serrano, D. R. (2017) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2017.04.013 · Cited by 78 · see citing works
Combinatorial Library of Lipidoids for In Vitro DNA Delivery
Sun, S., Wang, M., Knupp, S. A., Soto‐Feliciano, Y. M., Hu, X., Kaplan, D. L., Langer, R., Anderson, D. G., & Xu, Q. (2011) · Bioconjugate Chemistry · doi:10.1021/bc200572w · Cited by 71 · see citing works
Self-citationShao, K., Wu, J., Chen, Z., Huang, S., Li, J., Ye, L., Lou, J., Zhu, L., & Jiang, C. (2012) · Biomaterials · doi:10.1016/j.biomaterials.2012.06.050 · Cited by 61 · see citing works
Smith, P. J., Olson, J. A., Constable, D., Schwartz, J., Proffitt, R. T., & Adler‐Moore, J. (2007) · Journal of Antimicrobial Chemotherapy · doi:10.1093/jac/dkm077 · Cited by 58 · see citing works
A Combinatorial Library of Unsaturated Lipidoids for Efficient Intracellular Gene Delivery
Wang, M., Sun, S., Alberti, K. A., & Xu, Q. (2012) · ACS Synthetic Biology · doi:10.1021/sb300023h · Cited by 58 · see citing works
Self-citationZia, Q., Owais, M., Rauf, M. A., Khan, W., & Zubair, S. (2017) · Scientific Reports · doi:10.1038/s41598-017-11847-0 · Cited by 58 · see citing works
Optimization of Lipid Composition in Cationic Emulsion as In Vitro and In Vivo Transfection Agents
Kim, T. W., Chung, H., Kwon, I. C., Sung, H. C., & Jeong, S. Y. (2001) · Pharmaceutical Research · doi:10.1023/a:1011074610100 · Cited by 57 · see citing works
Risovic, V., Boyd, M. C., Choo, E., & Wasan, K. M. (2003) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.47.10.3339-3342.2003 · Cited by 48 · see citing works
Adedoyin, A. B., Swenson, C. E., Bolcsak, L. E., Hellmann, A. R., Radowska, D., Horwith, G., Janoff, A. S., & Branch, R. A. (2000) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.44.10.2900-2902.2000 · Cited by 45 · see citing works
Sheu, M., Chen, Y., Su, C.-Y., Jhan, H.-J., & Ho, H.-O. (2015) · International Journal of Nanomedicine · doi:10.2147/ijn.s95194 · Cited by 40 · see citing works
Tan, T. R. M., Hoi, K. M., Zhang, P., & Ng, S. K. (2016) · PLoS ONE · doi:10.1371/journal.pone.0152112 · Cited by 31 · see citing works
Keane, S., Geoghegan, P., Póvoa, P. M. S. R., Nseir, S., Rodríguez, A. H., & Martín‐Loeches, I. (2018) · Expert Review of Anti-infective Therapy · doi:10.1080/14787210.2018.1528872 · Cited by 27 · see citing works
Recent Progress on Antifungal Drug Development
Zhai, B., & Lin, X. (2011) · Current Pharmaceutical Biotechnology · doi:10.2174/138920111796117292 · Cited by 26 · see citing works
Bioactivity and toxicity studies of amphotericin B incorporated in liquid crystals
Chuealee, R., Aramwit, P., Noipha, K., & Srichana, T. (2011) · European Journal of Pharmaceutical Sciences · doi:10.1016/j.ejps.2011.05.009 · Cited by 23 · see citing works
Hoo, L. S. (2017) · Journal of Liposome Research · doi:10.1080/08982104.2017.1360345 · Cited by 22 · see citing works
Adler‐Moore, J., Proffitt, R. T., Olson, J. A., & Jensen, G. M. (2017) · Journal of Liposome Research · doi:10.1080/08982104.2017.1327543 · Cited by 18 · see citing works
Angra, P., Oettinger, C. W., Pai, S. B., & D’Souza, M. J. (2009) · Journal of Microencapsulation · doi:10.3109/02652040902797516 · Cited by 14 · see citing works
Patere, S. N., Pathak, P. O., Shukla, A. K., Singh, R. K., Dubey, V. K., Mehta, M., Patil, A., Gota, V. S., & Nagarsenker, M. S. (2016) · AAPS PharmSciTech · doi:10.1208/s12249-016-0553-8 · Cited by 14 · see citing works
Stott, K. E., Beardsley, J., Whalley, S., Kibengo, F., Hoang, N. T., Tung, N. L. N., Cuc, N. T. K., Kolamunnage‐Dona, R., Hope, W. W., & Day, J. (2018) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.02526-17 · Cited by 12 · see citing works
Formulaciones liposómicas de anfotericina B: diferencias basadas en la evidencia científica
Perea, J. R. A., de Rada, B. S. D., & Carvalho, J. R. (2015) · Revista española de quimioterapia. Suplemento · Cited by 9 · see citing works
Unilateral Blastomyces dermatitidis Optic Neuropathy
Pariseau, B., Lucarelli, M. J., & Appen, R. E. (2007) · Ophthalmology · doi:10.1016/j.ophtha.2007.05.017 · Cited by 9 · see citing works
Mariné, M., Espada, R., Torrado, J. J., Pastor, F., & Guarro, J. (2009) · International Journal of Antimicrobial Agents · doi:10.1016/j.ijantimicag.2009.07.005 · Cited by 6 · see citing works
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Zhang, Y., Sun, C., Wang, C., Jankovic, K. E., & Dong, Y. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.1c00244 · Cited by 638 · see citing works
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
“The AmB concentration in the brain tissue was quantified using high-performance liquid chromatography (HPLC) according to the method that previously reported ( 27 ).”
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Qiu, M., Li, Y., Bloomer, H., & Xu, Q. (2021) · Accounts of Chemical Research · doi:10.1021/acs.accounts.1c00500 · Cited by 168 · see citing works
Self-citationLi, Y., Ye, Z., Yang, H., & Xu, Q. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2022.04.013 · Cited by 99 · see citing works
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Wang, C., Lan, X., Zhu, L., Wang, Y., Gao, X., Li, J., Tian, H., Liang, Z., & Xu, W. (2024) · Small · doi:10.1002/smll.202309031 · Cited by 73 · see citing works
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Wu, S., Lin, L., Shi, L., & Liu, S. (2024) · Wiley Interdisciplinary Reviews Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1978 · Cited by 35 · see citing works
Zhao, X., Glass, Z., Chen, J., Yang, L., Kaplan, D. L., & Xu, Q. (2020) · Advanced Healthcare Materials · doi:10.1002/adhm.202000938 · Cited by 35 · see citing works
Self-citationLi, Y., Li, P., Li, R., & Xu, Q. (2020) · Advanced Therapeutics · doi:10.1002/adtp.202000178 · Cited by 31 · see citing works
Self-citationLi, Y., Li, R., Chakraborty, A., Ogurlu, R., Zhao, X., Chen, J., & Xu, Q. (2020) · Bioconjugate Chemistry · doi:10.1021/acs.bioconjchem.0c00295 · Cited by 25 · see citing works
Self-citationJi, W., Zhou, H., Liang, W., Zhang, W., Gong, B., Yin, T., Chu, J., Zhuang, J., Zhang, J., Luo, Y., et al. (2024) · Small · doi:10.1002/smll.202308574 · Cited by 22 · see citing works
Chen, Z., Gong, Y., Chen, F., Lee, H. J., Qian, J., Zhao, J. C., Zhang, W., Li, Y., Zhou, Y., Xu, Q., et al. (2024) · 癌症：英文版 · doi:10.1002/cac2.12644 · Cited by 13 · see citing works
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- Authors
- Liu, F., Yang, L., Li, Y., Junier, A., Ma, F., Chen, J., Han, H., Glass, Z., Zhao, X., Kumamoto, C. A., Sang, H., & Xu, Q.
- Affiliations
- Tufts University (US)
- Nanjing General Hospital of Nanjing Military Command (CN)
- Corresponding author
- Sang, Hong
- Xu, Qiaobing
- ORCID
- Venue
- ACS Biomaterials Science & Engineering
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-01-10
- Volume
- 6
- Issue
- 2
- Pages
- 1064-1073
- ISSN
- 2373-9878 (ISSN-L)
- OpenAlex
- W2999008125
- Cited by
- 21
- References
- 41
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 4
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Biomaterials Science & Engineering (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI118898)
- Lloyd Foundation
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- amphotericin B, DSPE-PEG2000, antifungal drug delivery, systemic fungal infection, nanoparticle stability, pharmacokinetics, nephrotoxicity, hepatotoxicity, hemotoxicity, drug toxicity reduction
- MeSH terms
- Amphotericin B, Animals, Antifungal Agents, Humans, Microbial Sensitivity Tests, Mycoses, Rats, Nanoparticles
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