Leishmaniasis (Kala Azar) is a parasitic infection caused by the Leishmaniasis parasite which is transmitted by sand fly bites. In the developing world, leishmaniasis affects an estimated 200-350 m people, with 20,000 - 60,000 patients dying every year from visceral leishmaniasis. Current first line treatment requires a 30 day course of intramuscular injections of pentavalent antimonials. Another treatment option is intravenous Amphotericin B, an effective drug for the treatment of these conditions, that has been available for 60 years. In contrast to some newer therapeutics the leishmaniasis parasites have so far not developed any resistance to Amphotericin B.
Amphotericin B is also used for the treatment of systemic fungal infections, e.g. in immunocompromised patients. In the Western Hemisphere, opportunistic systemic fungal infections affect neutropenic oncology patients (up to 5-10% of patients with haematological malignancies), organ transplant recipients, diabetics and HIV/AIDS sufferers.
However, Amphotericin B is not currently available in tablet form but requires repeat administration by intravenous infusion, instead. This severely limits the therapeutic potential of this drug in many poorer parts of the world where access to the necessary medical facilities is not readily available. Even in the West this also makes its prophylactic use, i.e. for the prevention of fungal infections in immunocompromised patients, impractical.
Nanomerics has developed a nano-enabled orally active form of Amphotericin B, NM147. NM147, given over 10 days, is as effective as the parenterally administered liposomal Amphotericin B in treating leishmaniasis, systemic aspergilosis and candidiasis in preclinical models. There are very few drug delivery systems that target key organs via the oral route, as oral delivery advances normally address gastrointestinal drug dissolution, permeation, and formulation stability challenges. Here we introduce a nanomedicine in which nanoparticles, while also protecting the drug from gastric degradation, are taken up by the gastrointestinal epithelia and transported to the lung, liver, and spleen, thus selectively enhancing drug bioavailability in these target organs and diminishing kidney exposure. This minimises any risk associated with this potentially nephrotoxic drug.
The oral bioavailability of NM147 is 24%. In all disease models, NM147 shows efficacy that is comparable to the commerical parenteral liposomal Amphotericin B (AmBisome). This demonstrates the potential of the MET nanoparticles to achieve a specific targeted delivery of drug to key organs via the oral route. This is especially important for drugs with a narrow therapeutic index. NM147 has the potential to improve the treatment of Leishmaniasis for millions of people living in endemic regions. In addition it also targets a number of important indications in the developed world, such as systemic forms of Candidiasis and Aspergillosis which in some cases are associated with a mortality of up to 90%.
The data has been published as a peer reviewed article .