|Author||Nishi, K. K. ♦ Antony, M. ♦ Mohanan, P. V. ♦ Anilkumar, T. ♦ Loiseau, P. M. ♦ Jayakrishnan, A.|
|Source||Sree Chitra Tirunal Institute for Medical Sciences & Technology|
|Subject Domain (in DDC)||Technology ♦ Medicine & health ♦ Pharmacology and therapeutics ♦ Diseases|
|Subject Domain (in MeSH)||Eukaryota ♦ Organisms ♦ Organic Chemicals ♦ Carbohydrates ♦ Complex Mixtures ♦ Chemicals and Drugs|
|Abstract||Purpose. Gum arabic, a branched polysaccharide consisting of more than 90% arabinogalactan having a molecular weight around 250,000 Da is the oldest and best known of all natural gums. The objective of the present investigation was to examine whether amphotericin B (AmB), the polyene antibiotic when conjugated to periodate oxidized gum arabic still retained its anti-fungal and anti-leishmanial activity and to evaluate its toxicity and bioavailability.Methods. AmB conjugated to the oxidized polysaccharide through Schiff's linkages in the unreduced (imine) and reduced (amine) forms were characterized for the drug content, hemolytic potential, molecular mass, in vitro release and were examined for anti-fungal activity against Candida albicans and Cryptococcus neoformans and for anti-leishmanial activity against promastigotes of Leishmania donovani in culture. Toxicity and bioavailability were evaluated by intravenous (i.v) injections of the conjugates in mice and rabbits respectively.Results. The conjugates were found to be non-hemolytic and mice withstood a dosage of 20 mg (AmB)/kg body weight of both conjugates. Histological examination of the internal organs of mice showed no lesions in kidney, brain, heart or liver. Estimation of the residual drug in the internal organs 7 days post injection showed that the spleen still retained 8.4 +/- 0.53 mu g/g of tissue. AmB was found to be released from both conjugates in vitro although the release from the imine conjugate was much faster than from the amine conjugate. The concentrations inhibiting parasite growth by 50% (IC50) values for the imine conjugate against promastigotes of L. donovani LV9 and DD8 strains were 0.37 +/- 0.04 and 1.44 +/- 0.18 mu M respectively. The IC50 values for the amine conjugates were much higher. The minimum inhibitory concentration (MIC) against C. albicans and C. neoformans was in the range of 0.5-0.9 mu g/mL for both imino and amino conjugates. The bioavailability of the conjugate in rabbits showed that the imine conjugate maintained a plasma concentration in the range of 20 to 5 mu g/mL while for the amine conjugate it was in the range of 17 to 3 mu g/mL over 24 h.Conclusions. The drug conjugates were stable, non-hemolytic and non-toxic to the internal organs of the animal and showed good anti-fungal and anti-leishmanial activity in vitro. In spite of the large molecular weight of the polysaccharide, AmB from the conjugates showed bioavailability after i.v injection. Since the highest concentration of AmB was found in the spleen after a single injection, these conjugates may have potential in anti-leishmanial therapy.|
|Education Level||UG and PG|
|Learning Resource Type||Article|
|Educational Framework||Medical Council of India (MCI)|
Ministry of Human Resource Development (MHRD) under its National Mission on Education through Information and Communication Technology (NMEICT) has initiated the National Digital Library of India (NDLI) project to develop a framework of virtual repository of learning resources with a single-window search facility. Filtered and federated searching is employed to facilitate focused searching so that learners can find out the right resource with least effort and in minimum time. NDLI is designed to hold content of any language and provides interface support for leading vernacular languages, (currently Hindi, Bengali and several other languages are available). It is designed to provide support for all academic levels including researchers and life-long learners, all disciplines, all popular forms of access devices and differently-abled learners. It is being developed to help students to prepare for entrance and competitive examinations, to enable people to learn and prepare from best practices from all over the world and to facilitate researchers to perform inter-linked exploration from multiple sources. It is being developed at Indian Institute of Technology Kharagpur.
NDLI is a conglomeration of freely available or institutionally contributed or donated or publisher managed contents. Almost all these contents are hosted and accessed from respective sources. The responsibility for authenticity, relevance, completeness, accuracy, reliability and suitability of these contents rests with the respective organization and NDLI has no responsibility or liability for these. Every effort is made to keep the NDLI portal up and running smoothly unless there are some unavoidable technical issues.
Ministry of Human Resource Development (MHRD), through its National Mission on Education through Information and Communication Technology (NMEICT), has sponsored and funded the National Digital Library of India (NDLI) project.
For any issue or feedback, please write to email@example.com