ABSTRACT
Amphotericin B (AMB) is used to treat both fungal and leishmanial infections, which are of major significance to human health. Clinical use of free AMB is limited by its nephrotoxicity, whereas liposomal AMB is costly and requires parenteral administration, thus development of novel formulations with enhanced efficacy, minimal toxicity and that can be applied via non-invasive routes is required. In this study we analysed the potential of non-ionic surfactant vesicles (NIV) given by nebulisation to deliver AMB to the lungs, liver and skin. Treatment with AMB-NIV resulted in significantly higher drug levels in the lungs and skin (p<0.05) compared to similar treatment with AMB solution but significantly lower plasma levels (p<0.05). Treatment with AMB-NIV resulted in a significant reduction in fungal lung burdens in a rat model of invasive pulmonary aspergillosis (p<0.05) compared to treatment with the carrier alone. Treatment with AMB-NIV but not AMB solution significantly suppressed Leishmania donovani liver parasite burdens (p<0.05) but could not inhibit the growth of cutaneous Leishmania major lesions. The results of this study indicate that aerosolised NIV enhanced pulmonary and hepatic delivery whilst minimising systemic exposure and toxicity.
Subject(s)
Amphotericin B/administration & dosage , Antifungal Agents/administration & dosage , Drug Carriers/administration & dosage , Leishmaniasis/drug therapy , Pulmonary Aspergillosis/drug therapy , Surface-Active Agents/administration & dosage , Aerosols , Animals , Cricetinae , Disease Models, Animal , Female , Firefly Luciferin/administration & dosage , Leishmaniasis/metabolism , Leishmaniasis/microbiology , Liver/metabolism , Liver/microbiology , Lung/metabolism , Lung/microbiology , Mesocricetus , Mice , Mice, Inbred BALB C , Pulmonary Aspergillosis/metabolism , Pulmonary Aspergillosis/microbiology , Rats , Rats, Sprague-DawleyABSTRACT
The anthropometric measurements of all children between 3-10 years of age (n=1427) attending eight private primary schools in Freetown were recorded together with accurate dates of birth. This was done to compare the anthropometric measurements of well nourished children in Sierra Leone to the NCHS references. The results of weight/age; height/age and weight/height showed no statistically significant variation from the NCHS values for children of the same age and sex. The sample population adequately represented the major and some minor ethnical groups of Sierra Leonean population. It is concluded therefore that in those populations in Sierra Leone where the children do vary significantly from the NCHS; this difference in their growth potential may be explained by environmental factors rather than ethnic differences from American children
