Polymeric micelles of pluronic F127 reduce hemolytic potential of amphiphilic drugs

[Display omitted] •Polymeric micelles of Pluronic F127 reduce hemolytic potential of amphiphilic drugs.•The composition of Pluronic copolymers influences the aggregation state of amphiphilic drugs.•Pluronic F127 concentration has a pronounced effect on the HePC hemolytic profile.•The amount of HePC-...

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Published in:Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2019-08, Vol.180, p.177-185
Main Authors: Feitosa, Valker Araujo, Almeida, Vinícius Cordeiro de, Malheiros, Barbara, Castro, Raphael Dias de, Barbosa, Leandro Ramos Souza, Cerize, Natalia Neto Pereira, Rangel-Yagui, Carlota de Oliveira
Format: Article
Language:English
Subjects:
Animals
Anti-< > >Hemolytic
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
Cethylpyridinium chloride
Cetrimonium - chemistry
Cetrimonium - pharmacology
Cetylpyridinium - chemistry
Cetylpyridinium - pharmacology
Cetyltrimethylammonium bromide
Dose-Response Relationship, Drug
Drug Carriers
Drug Compounding - methods
Erythrocytes - drug effects
Hemolysis
Hemolysis - drug effects
Micelles
Miltefosine
Phosphorylcholine - analogs & derivatives
Phosphorylcholine - chemistry
Phosphorylcholine - pharmacology
Poloxamer
Poloxamer - chemistry
Poloxamer - pharmacology
Sheep
Surface-Active Agents - chemistry
Surface-Active Agents - pharmacology
Triblock copolymer
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Summary:[Display omitted] •Polymeric micelles of Pluronic F127 reduce hemolytic potential of amphiphilic drugs.•The composition of Pluronic copolymers influences the aggregation state of amphiphilic drugs.•Pluronic F127 concentration has a pronounced effect on the HePC hemolytic profile.•The amount of HePC-loaded into polymeric micelles might be adjusted by varying the concentration of Pluronic F127.•SAXS data indicate that Pluronic F127 concentration plays an important role on the micelle structure. One of the main toxicities associated to intravenous administration of amphiphilic drugs is pronounced hemolytic activity. To overcome this limitation, we investigated the anti-hemolytic properties of polymeric micelles of Pluronics, triblock copolymers of poly(ethylene oxide) and poly(propylene oxide). We studied the encapsulation of the amphiphilic compound miltefosine (HePC) into polymeric micelles of Pluronics F108, F68, F127, L44, and L64. In vitro hemolysis indicated that, among the five copolymers studied, only F127 completely inhibited hemolytic effect of HePC at 50 μg/mL, this effect was also observed for other two amphiphilic molecules (cetyltrimethylammonium bromide and cethylpyridinium chloride). To better understand this interaction, we analyzed the HC50 (concentration causing 50% of hemolysis) for HePC free and loaded into F127 micelles. Copolymer concentration influenced the hemolytic profile of encapsulated HePC; for F127 the HC50 increased relative to free HePC (40 μg/mL) up to 184, 441, 736 and 964 μg/mL, for 1, 3, 6 and 9% F127, respectively. Interestingly, a linear relationship was found between HC50-HePC and F127 concentration. At 3% of F127, it is possible to load up to 300 μg/mL of HePC with no hemolytic effect. By achieving this level of hemolysis protection, a promising application is on the view, bringing the parenteral use of HePC and other amphiphilic drugs. Additionally, small-angle X-ray scattering (SAXS) was used to asses structural information on the interactions between HePC and F127 micelles.
ISSN:0927-7765
1873-4367
DOI:10.1016/j.colsurfb.2019.04.045