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The Journey of Nanotechnology in Product Development
Published in Cherry Bhargava, Amit Sachdeva, Pardeep Kumar Sharma, Smart Nanotechnology with Applications, 2020
Divya Thakur, Sheetu Wadhwa, Sachin Kumar Singh, Rajesh Kumar, Rohit Vij
Amphotericin B is a polyene anti-mycotic agent with activity against yeasts, molds, and even protozoan parasite Leishmania spp. It binds to the sterol present in the fungal cell membrane, i.e. ergosterol, which results in the creation of pores followed by ion leakage and finally fungal cell death. In 1950, an initial formulation of this drug, i.e. amphotericin B deoxycholate (DAmB), was developed and used for many decades. However, there were side effects associated with DAmB such as nephrotoxicity and infusion-linked reactions which urged the formulation scientists to devise a new formulation that retains the anti-fungal activity and reduces toxicity. In light of the above facts, a unilamellar liposomal-based structure for parenteral administration comprising three main ingredients, namely, soy phosphatidylcholine, distearoylphosphatidyl glycerol, and cholesterol (molar ratio – 2:0.8:1), was designed. Soy phosphatidylcholine, a lipid with a unique property of gel to liquid-crystal phase transition point, prevented the hydrolyses of the lipid component on exposure to human body temperature. Distearoylphosphatidyl glycerol was chosen because of the presence of the slight negative charge and fatty acid chain length similar to the hydrophobic part of amphotericin B. Amphotericin B was retained inside the lipid bilayer of liposomes as under the preparatory conditions (slightly acidic), the amino group of the drug with positive charge forms an ionic complex with distearoylphosphatidyl glycerol.
Nanomedicine: Could It Be a Boon for Pulmonary Fungal Infections?
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Biswajit Mukherjee, Ashique Al Hoque, Shreyasi Chakraborty, Leena Kumari, Somdatta Roy, Paramita Paul
In spite of several progresses made in this field, any vaccine for fungal infections is not yet available clinically. Several antifungal agents are currently available in the market for the treatment of pulmonary fungal infections. Among them, amphotericin B had been the drug of choice for most cases of fungal infections. However, its usage is limited due to serious adverse effects, the most significant one being nephrotoxicity. Liposomal formulation of amphotericin B is also developed, and it greatly reduces nephrotoxicity, but still, it encounters numerous drawbacks due to its non-targeted delivery via parenteral route. In addition, it gets rapidly cleared from the systemic circulation due to uptake by reticuloendothelial system, which cannot be overlooked (Bowden et al., 2002; Moen et al., 2009). Other chemotherapeutic agents found to be therapeutically effective for the treatment of pulmonary fungal infections include the newer second-generation triazole antifungals (voriconazole, posaconazole) and flucytosine. However, these drugs also suffer from several dose-dependent adverse effects such as hepatotoxicity, gastric disturbances, bone marrow suppression-characterized as leucopenia, thrombocytopenia, and/or pancytopenia, etc. (Cook & Confer, 2011).
Inhalation Drug Products Containing Nanomaterials
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Sandro R.P. da Rocha, Rodrigo S. Heyder, Elizabeth R. Bielski, Ailin Guo, Martina Steinmaurer, Joshua J. Reineke
There have been two different liposomal formulations of Amphotericin B: AmBisome® and Abelcet® that have gone through clinical trials to treat pulmonary fungal infections (Aspergillosis), for lung transplantations, and for leukemia. The main ingredient in Amphotericin B is a fungicidal against many human yeast and mold pathogens including Aspergillus, Candida, Mucor, Rhizopus, Cryptococcus, and against dimorphic fungi (Adler-Moore et al. 2017). The main mechanism of action is the binding of amphotericin B to ergosterol in fungal cell membranes forming pores that increase permeability to small molecules irreversibly damaging the fungal cell (Aversa et al. 2017). Its main limitation of use is due to its nephrotoxicity. Therefore, liposomal formulations were produced to limit the toxicity and improve solubility, resulting in improved clinical efficacy (Aversa et al. 2017). The two liposomal formulations that have been translated for pulmonary delivery and tested in clinical trials are AmBisome® and Abelcet®.
Synthetic polymannose as a drug carrier: synthesis, toxicity and anti-fungal activity of polymannose-amphotericin B conjugates
Published in Journal of Biomaterials Science, Polymer Edition, 2018
Arul Prakash Francis, Sneha Gurudevan, A. Jayakrishnan
Amphotericin B (AmB) is a frequently used anti-fungal agent to treat systemic fungal infections in immunocompromised individuals [11]. AmB is also used for the treatment of leishmaniasis, a macrophage-associated disease [12]. AmB remains the drug of choice due to its broad spectrum of activity [13]. However, the low therapeutic index, poor aqueous solubility, and toxicity, limits its efficacy in certain fungal lesions. Many polysaccharide-AmB conjugates have been reported that improve the solubility and therapeutic efficacy of AmB while reducing its toxicity. Thus, AmB has been conjugated to arabinogalactan [14,15], galactomannan [16], dextran [17], gum arabic [18], pectin [19] and sodium alginate [20].
Optimization of the freeze-drying process for microemulsion systems
Published in Drying Technology, 2019
Andreza Rochelle do Vale Morais Morais, Francisco Humberto Xavier-Jr., Éverton do Nascimento Alencar, Christian Melo de Oliveira, Nednaldo Dantas Santos, Arnóbio Antônio Silva-Júnior, Gillian Barratt, Eryvaldo Sócrates Tabosa do Egito
Amphotericin B (AmB) is the drug of choice for the treatment in immunodeficient patients affected by systemic fungal infections.[5] However, due to the high incidence of adverse drug reactions, i.e., cardiotoxicity and hepatotoxicity of conventional formulations,[6] AmB has been incorporated into a number of colloidal drug delivery systems, including MEs, in order to improve its therapeutic index.[7,8]