Linolenic acid-modified methoxy poly (ethylene glycol)-oligochitosan conjugate micelles for encapsulation of amphotericin B
- Resource Type
- Authors
- Li Zhu; Runliang Feng; Peizong Deng; Yi Wen; Hongmei Xu; Sijia Feng; Feilong Zhou; Fangfang Teng; Zhimei Song
- Source
- Carbohydrate Polymers. 205:571-580
- Subject
- Male
Antifungal Agents
Erythrocytes
Linolenic Acids
Polymers and Plastics
Polymers
Linolenic acid
animal diseases
Oligosaccharides
Chitin
02 engineering and technology
Kidney
010402 general chemistry
Hemolysis
01 natural sciences
Micelle
Polyethylene Glycols
Rats, Sprague-Dawley
Mice
chemistry.chemical_compound
Pharmacokinetics
Amphotericin B
Candida albicans
parasitic diseases
Materials Chemistry
medicine
Animals
Micelles
Chitosan
Drug Carriers
biology
urogenital system
Chemistry
Organic Chemistry
technology, industry, and agriculture
bacterial infections and mycoses
021001 nanoscience & nanotechnology
biology.organism_classification
0104 chemical sciences
Drug Liberation
Drug delivery
0210 nano-technology
Ethylene glycol
Nuclear chemistry
medicine.drug
Conjugate
- Language
- ISSN
- 0144-8617
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.