Synthetic polymannose as a drug carrier: synthesis, toxicity and anti-fungal activity of polymannose-amphotericin B conjugates.
J Biomater Sci Polym Ed
; 29(13): 1529-1548, 2018 09.
Article
en En
| MEDLINE
| ID: mdl-29683392
Polymannose (PM) having a weight-average molar mass (Mw) of 30-53 kDa was synthesized by the polycondensation of mannose using phosphorous acid as the catalyst and characterized by various techniques such as NMR, IR, GPC and polarimetry. 2D NMR results confirmed the presence of (1 â 6)-linked α-D-mannose residues as backbone with O-3 and O-2 substituted linear or branched chains in PM. Amphotericin B (AmB) was conjugated to periodate-oxidized PM through Schiff's linkages at 20 wt% concentration. The AmB-PM conjugates were highly soluble in phosphate buffered saline (180-250 mg/mL), exhibited negligible hemolytic potential to human erythrocytes even at a concentration of 200 µg/mL (equivalent to ~40 µg/mL AmB) and were non-toxic to human embryonic kidney (HEK293T) cells even at a concentration of 250 µg/mL (equivalent to ~50 µg/mL AmB). The minimum inhibitory concentration of the AmB-PM conjugates against C. albicans, C. parapsilosis and C. neoformans was in the range of 0.5-1.0 µg/mL. Mannose receptors are widely expressed on myeloid cells such as macrophages, neutrophils, and dendritic cells. Therefore, apart from treating fungal infections, AmB-PM conjugates also may have therapeutic potential for the treatment of macrophage-associated diseases such as leishmaniasis where mannose receptors are overexpressed.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Portadores de Fármacos
/
Anfotericina B
/
Mananos
/
Antifúngicos
Límite:
Humans
Idioma:
En
Revista:
J Biomater Sci Polym Ed
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
India
Pais de publicación:
Reino Unido