Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Springer
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB(2) miktoarms [A = hydrophobic poly(-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and Cu-I catalyzed azide-alkyne cycloaddition. Characterization by H-1 and C-13 NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB(2) miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG(2)) and blank micelles (PCL-PEG(2)) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG(2)) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG(2)) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 mu g/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG(2) and ITZ-PCL-PEG(2) inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG(2) revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG(2) micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.
Açıklama
Anahtar Kelimeler
Micelles, Itraconazole, Acanthamoeba, Nanoformulation, Central Nervous System, Infectious Diseases, Free-Living Amoebae, Nanotechnology
Kaynak
Archives of Microbiology
WoS Q Değeri
N/A
Scopus Q Değeri
Q2
Cilt
206
Sayı
4
