Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles

Ying Chen Chen, Chia Yu Su, Hua Jun Jhan, Hsiu O. Ho, Ming Thau Sheu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic®, Kolliphor®, d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14%, and 7.51%, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone®, the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solution or Fungizone® did. With pretreatment of 50 μg/mL ethanolic extract of Taiwanofungus camphoratus followed by AmB to HT29 colon cancer cells, the 50% inhibitory concentration of AmB solution was 12 μg/mL, whereas that of Ambicelles was 1 μg/mL, indicating that Ambicelles exerted a greater synergistic anticancer effect.

Original languageEnglish
Pages (from-to)7265-7274
Number of pages10
JournalInternational Journal of Nanomedicine
Volume10
DOIs
Publication statusPublished - Dec 2 2015

Fingerprint

Lecithin
Pharmacokinetics
Lecithins
Micelles
Amphotericin B
Polyethylene glycols
Solubility
Cells
Cytotoxicity
Encapsulation
Particle size
Polymers
Water
Poloxamer
Particle Size
Pharmaceutical Preparations
Colonic Neoplasms
Biological Availability
Inhibitory Concentration 50
Cell Survival

Keywords

  • Amphiphilic polymer
  • Amphotericin B
  • DSPE-PEG
  • Lecithin
  • Micelle

ASJC Scopus subject areas

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Organic Chemistry
  • Drug Discovery

Cite this

Physical characterization and in vivo pharmacokinetic study of self-assembling amphotericin B-loaded lecithin-based mixed polymeric micelles. / Chen, Ying Chen; Su, Chia Yu; Jhan, Hua Jun; Ho, Hsiu O.; Sheu, Ming Thau.

In: International Journal of Nanomedicine, Vol. 10, 02.12.2015, p. 7265-7274.

Research output: Contribution to journalArticle

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abstract = "To alleviate the inherent problems of amphotericin B (AmB), such as poor water solubility and nephrotoxicity, a novel self-assembling mixed polymeric micelle delivery system based on lecithin and combined with amphiphilic polymers, Pluronic{\circledR}, Kolliphor{\circledR}, d-alpha tocopheryl polyethylene glycol succinate, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy(poly(ethylene glycol)-2000 (DSPE-PEG2K) was developed. An optimal formulation (Ambicelles) composed of AmB:lecithin:DSPE-PEG2K in a 1:1:10 weight ratio was obtained. The particle size, polydispersion index, drug encapsulation efficiency, and drug loading were 187.20±10.55 nm, 0.51±0.017, 90.14{\%}, and 7.51{\%}, respectively, and the solubility was increased from 0.001 to 5 mg/mL. Compared with that of Fungizone{\circledR}, the bioavailability of Ambicelles administered intravenously and orally increased 2.18- and 1.50-fold, respectively. Regarding the in vitro cytotoxicity, Ambicelles had a higher cell viability than free AmB solution or Fungizone{\circledR} did. With pretreatment of 50 μg/mL ethanolic extract of Taiwanofungus camphoratus followed by AmB to HT29 colon cancer cells, the 50{\%} inhibitory concentration of AmB solution was 12 μg/mL, whereas that of Ambicelles was 1 μg/mL, indicating that Ambicelles exerted a greater synergistic anticancer effect.",
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