PURPOSE: The aim of this work was to demonstrate an immunostimulatory and adjuvant effect of new apyrogenic lipophilic derivatives of norAbuMDP and norAbuGMDP formulated in nanoliposomes. METHODS: Nanoliposomes and metallochelating nanoliposomes were prepared by lipid film hydration and extrusion methods. The structure of the liposomal formulation was studied by electron microscopy, AF microscopy, and dynamic light scattering. Sublethal and lethal γ-irradiation mice models were used to demonstrate stimulation of innate immune system. Recombinant Hsp90 antigen (Candida albicans) bound onto metallochelating nanoliposomes was used for immunisation of mice to demonstrate adjuvant activities of tested compounds. RESULTS: Safety and stimulation of innate and adaptive immunity were demonstrated on rabbits and mice. The liposomal formulation of norAbuMDP/GMDP was apyrogenic in rabbit test and lacking any side effect in vivo. Recovery of bone marrow after sublethal γ-irradiation as well as increased survival of mice after lethal irradiation was demonstrated. Enhancement of specific immune response was demonstrated for some derivatives incorporated in metallochelating nanoliposomes with recombinant Hsp90 protein antigen. CONCLUSIONS: Liposomal formulations of new lipophilic derivatives of norAbuMDP/GMDP proved themselves as promising adjuvants for recombinant vaccines as well as immunomodulators for stimulation of innate immunity and bone-marrow recovery after chemo/radio therapy of cancer.

• MeSH
• acetylmuramyl-alanyl-isoglutamin aplikace a dávkování   analogy a deriváty   chemie   farmakologie   terapeutické užití   MeSH
• adaptivní imunita účinky léků   MeSH
• adjuvancia imunologická aplikace a dávkování   chemie   farmakologie   terapeutické užití   MeSH
• analýza přežití MeSH
• antigeny fungální imunologie   MeSH
• experimentální radiační poranění imunologie   prevence a kontrola   MeSH
• králíci MeSH
• liposomy MeSH
• mikroskopie atomárních sil MeSH
• mikroskopie elektronová rastrovací MeSH
• molekulární struktura MeSH
• myši inbrední ICR MeSH
• myši MeSH
• nanočástice MeSH
• nosiče léků chemie   MeSH
• přirozená imunita účinky léků   MeSH
• proteiny tepelného šoku HSP90 imunologie   MeSH
• protilátky fungální krev   MeSH
• rekombinantní proteiny imunologie   MeSH
• transmisní elektronová mikroskopie MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylmuramyl-alanyl-isoglutamin MeSH
• adjuvancia imunologická MeSH
• antigeny fungální MeSH
• glucosaminylmuramyl-2-alanine-D-isoglutamine MeSH Prohlížeč
• liposomy MeSH
• N-acetylmuramyl-aminobutyryl-isoglutamine MeSH Prohlížeč
• nosiče léků MeSH
• proteiny tepelného šoku HSP90 MeSH
• protilátky fungální MeSH
• rekombinantní proteiny MeSH

An increased infection incidence of Candida albicans (most common human fungal pathogen) contributes to the need of further functional genetic studies and development of new antifungal drugs. We developed a method to create mutants of C. albicans using an antisense cDNA library to interfere with gene expression, followed by screening for hypersensitivity to Calcofluor White (CFW) and the antifungal drugs caspofungin and itraconazole. Mutants with these properties have with a high probability defects in cell-wall integrity. Fifty out of 200 transformant colonies analyzed (25%) showed hypersensitivity to CFW compared with the parental strain C. albicans CAI-4. Most of those CFW-hypersensitive mutants further displayed the susceptibility to antifungal drugs itraconazole and caspofungin using microbroth dilution method M27-A and an agar-diffusion test. The mutants obtained through this procedure could provide a potential model for screening antifungal pro-drugs which show weak action when standard C. albicans strain is used and may also aid in further identifying genes involved in cell integrity. In addition, we describe the effect of varying several parameters in electroporation transformation, including treatment with lithium acetate, upon the efficiency of transformation in C. albicans.

• MeSH
• antifungální látky farmakologie   MeSH
• buněčná stěna účinky léků   genetika   MeSH
• Candida albicans účinky léků   genetika   MeSH
• echinokandiny farmakologie   MeSH
• kaspofungin MeSH
• lipopeptidy MeSH
• mikrobiální testy citlivosti MeSH
• mutace MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antifungální látky MeSH
• echinokandiny MeSH
• kaspofungin MeSH
• lipopeptidy MeSH