TY - JOUR
T1 - Design of mannosylated oral amphotericin B nanoformulation
T2 - efficacy and safety in visceral leishmaniasis
AU - Sarwar, Hafiz Shoaib
AU - Sohail, Muhammad Farhan
AU - Saljoughian, Noushin
AU - Rehman, Anees Ur
AU - Akhtar, Sohail
AU - Nadhman, Akhtar
AU - Yasinzai, Masoom
AU - Gendelman, Howard E.
AU - Satoskar, Abhay R.
AU - Shahnaz, Gul
N1 - Funding Information:
This work is supported by the UNESCO-L’Oréal International Fellowship for Young Women in Life Sciences [SC/PCB/SPR/CDC/14.09] and TWAS–COMSTECH Joint Research Grant No. 15–304 RG/PHA/AS_C – FR3240288939.
PY - 2018/10/31
Y1 - 2018/10/31
N2 - The aim of this study was to evaluate mannose-anchored thiolated chitosan (MTC) based nanocarriers (NCs) for enhanced permeability, improved oral bioavailability and anti-parasitic potential of amphotericin B (AmB). Transgenic Leishmania donovani parasites expressing red fluorescent protein DsRed2 and imaging-flow cytometry was used to investigate parasitic burdens inside bone marrow-derived macrophages ex vivo. Cytokine estimation revealed that MTC nanocarriers activated the macrophages to impart an explicit immune response by higher production of TNF-α and IL-12 as compared to control. Cells treated with MTC NCs showed a significantly higher magnitude of nitrite and propidium iodide (PI) fluorescence intensity in contrast to cells treated with AmB. Concerning to apparent permeability coefficient (P app ) results, the MTC NCs formulation displayed more specific permeation across the Caco-2 cell monolayer as compared to AmB. The half-life of MTC NCs was about 3.3-fold persistent than oral AmB used as positive control. Also, t oral bioavailability of AmB was increased to 6.4-fold for MTC NCs compared to AmB for positive control. Acute oral evaluation indicated that MTC NCs were significantly less toxic compared to the AmB. Based on these findings, MTC NCs seems to be promising for significant oral absorption and improved oral bioavailability of AmB in leishmaniasis chemotherapy.
AB - The aim of this study was to evaluate mannose-anchored thiolated chitosan (MTC) based nanocarriers (NCs) for enhanced permeability, improved oral bioavailability and anti-parasitic potential of amphotericin B (AmB). Transgenic Leishmania donovani parasites expressing red fluorescent protein DsRed2 and imaging-flow cytometry was used to investigate parasitic burdens inside bone marrow-derived macrophages ex vivo. Cytokine estimation revealed that MTC nanocarriers activated the macrophages to impart an explicit immune response by higher production of TNF-α and IL-12 as compared to control. Cells treated with MTC NCs showed a significantly higher magnitude of nitrite and propidium iodide (PI) fluorescence intensity in contrast to cells treated with AmB. Concerning to apparent permeability coefficient (P app ) results, the MTC NCs formulation displayed more specific permeation across the Caco-2 cell monolayer as compared to AmB. The half-life of MTC NCs was about 3.3-fold persistent than oral AmB used as positive control. Also, t oral bioavailability of AmB was increased to 6.4-fold for MTC NCs compared to AmB for positive control. Acute oral evaluation indicated that MTC NCs were significantly less toxic compared to the AmB. Based on these findings, MTC NCs seems to be promising for significant oral absorption and improved oral bioavailability of AmB in leishmaniasis chemotherapy.
KW - Oral bioavailability
KW - acute toxicity
KW - mannose receptors
KW - permeation
KW - thiolated chitosan nanocarriers
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UR - http://www.scopus.com/inward/citedby.url?scp=85041307472&partnerID=8YFLogxK
U2 - 10.1080/21691401.2018.1430699
DO - 10.1080/21691401.2018.1430699
M3 - Article
C2 - 29385910
AN - SCOPUS:85041307472
VL - 46
SP - 521
EP - 531
JO - Artificial Cells, Nanomedicine and Biotechnology
JF - Artificial Cells, Nanomedicine and Biotechnology
SN - 2169-1401
IS - sup1
ER -