Journal
CARBOHYDRATE POLYMERS
Volume 205, Issue -, Pages 571-580Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2018.10.086
Keywords
Amphotericin B; Linolenic acid; Chitosan; Methoxy poly (ethylene glycol); Antifungal
Categories
Funding
- Natural Science Foundation of Shandong Province [ZR2016BL15]
- Science and Technology Project of University of Jinan [XKY1732]
- Shandong Talents Team Cultivation Plan of University Preponderant Discipline [10027]
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Introduction of linolenic acid (LNA) and methoxy poly (ethylene glycol) (MPEG) to the backbone of oligochitosan (CS) afforded LNA-modified MPEG-CS conjugate (MPEG-CS-LNA). Amphotericin B-loaded MPEG-CS-LNA micelles (AmB-M) were prepared via dialysis method with 82.27 +/- 1.96% of drug encapsulation efficiency and 10.52 +/- 0.22% of drug loading capacity. The AmB-M enhanced AmB's water-solubility to 1.64 mg/mL, being 1640-folds higher than native AmB. The AmB-M obviously reduced hemolytic effect and renal toxicity of AmB when compared to marketed AmB injection (AmB-I). Its antifungal activity against Candida albicans was equivalent to AmB-I although AmB's release from AmB-M was significantly retarded. According to fluorescence microscopy test, the unchanged activity should be attributed to enhanced fungal cellular uptake of AmB-M caused by combined inducement of LNA and CS. The pharmacokinetic studies demonstrated that AmB-M also improved the pharmacokinetic parameters of AmB with AmB-I as control. Conclusively, developed LNA-modified MPEG-CS micellar system could be a viable alternative to the current toxic commercial AmB-I as a highly efficacious drug delivery system.
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