Uro-Angiographic Contrast Agents—The Holy Grail
Christoph de Haën in X-Ray Contrast Agent Technology, 2019
Räth early on convinced his superior to give him the chance to pursue his own academic career, which required research in an area distinct from that of the chairman of the institute and eventual presentation thereof in the form of a habilitation dissertation.60 There is ample evidence that he was granted the necessary independence. Later Binz reported that his assistant was charged with guiding the group involved in veterinary chemotherapeutic exploitation of iodine derivatives of pyridine (Binz [1930] 1931, 1937a). A total of 73 such chemicals were synthesized (Binz [1930] 1931, 1937b). In contrast to the codification of arsenical and antimonial compounds, whose numbers were preceded by the letters B. R., the numbers for iodinated ones were preceded by only the letter R (e.g., Dahmen 1927), indicating that Räth after 1924 was alone running the iodine-based program. In some publications compounds were instead designated simply with ad hoc roman numerals, a common practice in chemistry journals. He was also permitted to patent some corresponding inventions by himself, an opportunity he, with the help of industry, did not allow to escape (Räth 1924c, 1925, 1927b).61
Lipid-Based Nanocarriers for the Treatment of Infected Skin Lesions
Andreia Ascenso, Sandra Simões, Helena Ribeiro in Carrier-Mediated Dermal Delivery, 2017
Regrettably, these efforts have not yet been completely successful and vaccination is still under experimental and clinical trials [53,54]. In the absence of a vaccine, chemotherapy remains the most efficient way to treat CL. However, the therapeutic arsenal is very limited and there is no single optimal treatment for all forms of this disease. The parenteral administration of pentavalent antimonials such as sodium stibogluconate (Pentostam®) and meglumine antimoniate (Glucantime®) have been the first-line treatment for over 50 years. For example, WHO recommends the administration of 20 mg/kg per day for 20 days of antimonials for New World CL [55–57]. Despite their widespread usage, these drugs have proved inconsistency in their effectiveness across different Leishmania species [58]. In addition, antimonial treatments are accompanied by painful administration, need of long course treatments and severe adverse reactions, such as cardiac and renal toxicity [59–61].
Antimonial Agents
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
Given the high risk of side effects and the variable treatment response in CL, treatment with Sb5+ is not recommended for those over the age of 50 or if there is any established organ dysfunction (WHO, 2010). Preexisting renal and hepatic dysfunction is common in VL, and would be expected to improve with effective chemotherapy. In a patient with significant renal impairment, drug excretion was shown to still be primarily via the urine at a rate matching the patient’s glomerular filtration rate (16 ml/min). Despite the prolonged half-life of 15 hours as compared to 2 hours in normal renal function, there was no significant rise in residual plasma levels and no severe adverse effects over 28 days of therapy with 25 mg/kg/day of MGA (Buffet et al., 1995). The authors suggest adjusting dosage to creatinine clearance, but no specific guidelines exist. Given the potential renal and hepatotoxic effects of pentavalent antimonials, extreme care should be exercised when using these agents in patients with preexisting organ dysfunction, and an increased frequency of monitoring will be required if antimonial treatment is considered necessary.
Sodium stibogluconate loaded nano-deformable liposomes for topical treatment of leishmaniasis: macrophage as a target cell
Published in Drug Delivery, 2018
M. Junaid Dar, Fakhar Ud Din, Gul Majid Khan
In vitro cytotoxicity assay was performed to establish whether the drug concentration used on amastigotes was toxic to the macrophages itself or not. It was expected that nano-formulations would be more biocompatible because drug entrapment inside the vesicles would minimize the direct exposure of SSG to the normal cells. However, the assay revealed that the CC50 values for SSG and SSG-NDLs were 1.65 and 1.3 mg/ml, respectively. The comparison of CC50 values indicated that there was 21.2% reduction in CC50 of SSG-NDLs in comparison to free SSG as shown in Figure 3(a). Generally, the active form of antimony (Sb-III) is toxic to the body and therefore the antimonial preparations come in the form of Sb-V, complexed in the form of sodium stibogluconate and meglumine. Once inside the macrophages, Sb-V complexes are reduced to Sb-III and act against amastigotes which may produce cytotoxic effects (Borborema et al., 2011). This reduction in CC50 value verified our claim of higher cellular uptake of SSG-NDLs in comparison to plain SSG and might be the possible reason for this reduction.
Use of liposomal nanoformulations in antileishmania therapy: challenges and perspectives
Published in Journal of Liposome Research, 2021
Jair Téllez, Maria Clara Echeverry, Ibeth Romero, Andrea Guatibonza, Guilherme Santos Ramos, Ana Carolina Borges De Oliveira, Frédéric Frézard, Cynthia Demicheli
The main feature that makes liposomes ideal vehicles of drug delivery molecules inside the macrophages is their capacity of being digested in the body by phagocytic cells after internalization. The best-known cases of this ‘Trojan horse’ mechanism, are parasitic diseases that normally use mononuclear phagocytic system (MPS) cells as vehicles, such as the infections caused by the different species of Leishmania spp (New et al. 1978, Shaheen et al. 2006). In the 1970s, an important advance in the use of liposomes for VL treatment was reported (Black et al. 1977). In this study antimonial drugs encapsulated in liposomes showed an effective increment in vivo against experimental VL, compared to non-encapsulated drugs. The increased leishmanicidal effect of the encapsulated antimonial was mainly attributed to two different phenomena: (i) a prolonged drug presence in the organism, due to liposomes circulation in the blood, and (ii) a natural process of liposome recognition by liver and spleen macrophages, which releases the encapsulated drug inside the cells (Alving 1986). These phenomena induce a significant decrease of parasites in the macrophage cells, which are the main sites of infection by Leishmania spp.
Pharmaceutical agents for treatment of leishmaniasis: a patent landscape
Published in Expert Opinion on Therapeutic Patents, 2020
Yasmim Maria Barbosa Gomes de Carvalho, Saravanan Shanmugam, Mayrton Santos Batista, Mairim Russo Serafini, Adriano Antunes De Souza Araújo, Lucindo José Quintans Júnior
In the patent number WO 2015177820 [41], the inventors developed polymeric nanoparticle systems as effective vehicles for compounds containing antimony, also antimonials, such as N-methylglucamine antimoniate (Glucantime®), which was entrapped in the aqueous ‘core’ of nanocapsules having an external layer, or ‘shell’ of polylactic acid. This pharmaceutical formulation allowed transport of compound within the guest’s macrophages, thus avoiding the appearance of the typical toxic systemic effects linked to the therapy with antimonial drugs there. To confirm the surprising ability to nanocapsules, this invention showed that microphotograph of J774A cells treated for 1 hour, bringing about a remarkable decrease of the pentavalent antimonial compound an increase in effectiveness. The treatment with the equivalent of 50 µM of Sbv vehiculated by the nanocapsules, induced a remarkable decrease of parasites with respect to control, and small morphological changes. Therefore, the nanoparticles of the invention allowed preserving the pharmacological activity of the antimonial drug by decreasing its accumulation in heart and kidney tissues, which cause serious side and undesired affects seen in vivo. The pharmaceutical formulations containing the nanocapsules of the invention can comprise carriers; stabilizers chelating agents; antimicrobial agents; and all the excipients acceptable for the preparation of drugs for parenteral use.
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