Lifecare Innovations Private Limited

FUNGISOME™

FUNGISOME™ in the treatment of Leishmaniasis (Kala-Azar)

Leishmaniasis is caused by macrophage resident intracellular protozoan parasites Leishmania donovani, Leishmania infantum and Leishmania chagasi. Parasite transmission occurs through the bite of infected female phlebotomine sandfly. Sandflies obtain infected blood while sucking the blood from their parasite carrier hosts. Four different forms of leishmaniasis with different clinical manifestations occur in humans. Of these different forms, visceral leishmaniasis (VL) which is also known as Kala-Azar is the most severe and has a mortality rate of almost 100% if not treated. Frequent bouts of fever, weight loss, enlargement of spleen and liver accompanied with anemia are characteristic signs and symptoms of VL.

Various social and lifestyle changes have altered the epidemiology of VL which was earlier predominant only in underdeveloped tropical countries. Leishmaniasis is presently endemic in all continents except Australia. According to an earlier report of World Health Organisation there are in excess of 12 million people affected by leishmaniasis world wide and nearly 2 million new cases are added each year. One third of the new cases of leishmaniasis are VL and 90% of the VL cases are in five countries Bangladesh, Brazil, India, Nepal and Sudan. Indian alone accounts for 1/4th of the total world wide incidents.

Kala-Azar is a major public health problem in certain part of India. Standard treatment involves use of Antimonials and Sodium Stibogluconate. Considerable resistance to the standard drugs has compelled to look for alternative drugs. AmphotericinB has been found clinically effective even in resistant cases of Kala-Azar. Use of AmphotericinB, however, is restricted due to its well known toxicities.

Strategic suitability of lipid formulations of AmphotericinB for the treatment of visceral leishmaniasis emanates from several factors viz. leishmania resides in the macrophages, liposomes are rapidly taken up by the macrophages, AmphotericinB is an effective antileishmanial drug, and AmphotericinB can be formulated as liposomal preparation. All of these facilitate targeted delivery of Liposomal AmphotericinB to the desired site for antiparasitic action and thus reduces the toxicities of the AmphotericinB. Additionally liposomes offer an amplification effect, through concentrated encapsulation of numerous molecules in each liposomes particle which are delivered at the desired site of action. Liposomal AmphotericinB has been used extensively throughout the world as the best option for treatment of VL even in cases resistant to standard drugs. FUNGISOME™ has been shown to have proven advantage over conventional drug regimen in the treatment of visceral leishmaniasis in India.

Tissue distribution of FUNGISOME™ has been studied in experimental animals infected with Leishmania donovani. At the maximum tolerated doses of conventional AmphotericinB and FUNGISOME™ higher levels of AmphotericinB were achieved in liver and spleen in the mice treated with FUNGISOME™. In comparison, conventional AmphotericinB was found to be less effective at the tolerated doses.

Taking into consideration economy of the treatment, number of dosage schedules have been clinically evaluated which are comprehensively presented below.

Dosage Schedule	AmphotericinB in FUGNISOME™ (mg/kg body wt/day)	Treatment duration (No. of days)	Total Dose (mg/kg body wt)
1	1	21	21
2	2	7-10	14-20
3	3	5-7	15-21

It is necessary to ensure parasite clearance before concluding the treatment. Additional doses are recommended if the parasitemia persists.

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