US food and drug administration approval of liposomal amphotericin B for the treatment of visceral leishmaniasis: A model for orphan drug development

Liposomes used as a vaccine adjuvant-delivery system: From basics to clinical immunization

“…Encouraged by this, combined with great achievements in optimization of liposome formulations, such as control of vesicle size, and lyophilisation of stable dry products with disaccharides as a lyoprotectant, scientists eventually brought to European markets in 1990 the first therapeutic liposomal product, Ambisome®. It is amphotericin B-loaded SUVs with the optimized formulation of HSPC/CHO/DSPG/amphotericin B (5:2.5:2:1, mole ratio) and a size of around 40 nm, and was later authorized in USA in 1997, to treat systemic fungal infections and certain protozoan infections such as visceral leishmaniasis and primary amoebic meningoencephalitis [148,149]. Meanwhile, two breakthrough techniques, remote loading drugs into liposomes and PEGylation of liposome surfaces, were achieved and matured to clear, in the development of liposomal products, the longstanding crucial barriers, including poor encapsulation of drugs, instability of an aqueous suspension of liposomes, and very short circulation time of in vivo liposomes due to rapid removal conducted by mononuclear phagocytic system (MPS) after systemic injection.…”

Nanocarriers for intravenous injection—The long hard road to the market

“…This preparation for the treatment of visceral leishmaniasis was the first product for this indication in the US. It demonstrated the willingness of the FDA to evaluate the efficacy and toxicity of an orphan compound (Pearson et al, 1999) and was a dooropener for the use of liposomal parenterals. 290 M a n u s c r i p t 10 The approval of Doxil ® , a parenteral liposome-based drug formulation for cancer therapy followed in 1995.…”

New challenges in the epidemiology and treatment of visceral leishmaniasis in periurban areas

“…Liposomal amphotericin B for the treatment of visceral leishmaniasis in the United States is a drug approved by the Food and Drug Administration [Pearson et al, 1999, Murray et al, 2005], and is the drug of choice in most industrialized countries and more recently in other countries as its cost has decreased [Sundar et al, 2008; Mueller et al, 2006]. The recommended dosage for liposomal amphotericin B in immunocompetent people is 3mg/kg body weight daily on days 1 through 5, 14, and 21.…”

“…Ninety percent of VL cases occur in India, Bangladesh, Sudan, Nepal and Brazil. Post-kala-azar dermal leishmaniasis (PKDL) is a complication of VL, usually developing after therapy [Pearson et al, 1999]. VL is commonly caused by the Leishmania donovani complex.…”