Amphotericin B-loaded deformable lipid vesicles for topical treatment of cutaneous leishmaniasis skin lesions

Carvalheiro, Manuela; Vieira, Jennifer; Faria-Silva, Catarina; Marto, Joana; Simões, Sandra

doi:10.1007/s13346-021-00910-z

Cited by 7 publications

(4 citation statements)

References 47 publications

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“…Perez et al [ 104 ] noticed that the insertion of AmB reduced vesicle deformability. This finding is in line with other reports in the literature and can be explained by the interaction of AmB with the lipids and edge activators, reducing their mobility [ 88 , 104 , 105 , 106 ]. As shown by the authors, the increase in AmB content, in addition to reducing the deformability, modified the absorption spectrum, suggesting AmB self-association in liposome bilayers.…”

Section: Topical Liposomal Formulations Of Ambsupporting

confidence: 93%

“…This probably explains the improved in vitro skin penetration of AmB from this formulation, in comparison to the AmBisome ® . Carvalheiro et al [ 105 ] conducted studies evaluating liposomes of similar composition, confirming that ultra-deformable liposomes promoted increased drug penetration into the skin. In addition, Peralta et al [ 88 ] also showed that this type of liposome provided better drug penetration into/through human skin than conventional ones.…”

Section: Topical Liposomal Formulations Of Ambmentioning

confidence: 94%

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Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations

et al. 2022

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The liposomal amphotericin B (AmB) formulation, AmBisome®, still represents the best therapeutic option for cutaneous and visceral leishmaniasis. However, its clinical efficacy depends on the patient’s immunological status, the clinical manifestation and the endemic region. Moreover, the need for parenteral administration, its side effects and high cost significantly limit its use in developing countries. This review reports the progress achieved thus far toward the understanding of the mechanism responsible for the reduced toxicity of liposomal AmB formulations and the factors that influence their efficacy against leishmaniasis. It also presents the recent advances in the development of more effective liposomal AmB formulations, including topical and oral liposome formulations. The critical role of the AmB aggregation state and release rate in the reduction of drug toxicity and in the drug efficacy by non-invasive routes is emphasized. This paper is expected to guide future research and development of innovative liposomal formulations of AmB.

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Section: Topical Liposomal Formulations Of Ambsupporting

confidence: 93%

Section: Topical Liposomal Formulations Of Ambmentioning

confidence: 94%

Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations

et al. 2022

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“…Second-line medications are pentamidine (PTM) and amphotericin B, which work by inhibiting DNA and sterol biosynthetic pathways, respectively [ 44 ]. PTM is no longer used due to toxic side effects in humans and drug resistance in parasites, while amphotericin B treatment requires hospitalization and high cost due to the requirement of lipid formulation [ 45 , 46 ]. Other medications used to treat Leishmania include miltefosine and paromomycin.…”

Section: Discussionmentioning

confidence: 99%

Repurposing Lansoprazole and Posaconazole to treat Leishmaniasis: Integration of in vitro testing, pharmacological corroboration, and mechanisms of action

Gupta¹,

Goicoechea²,

Romero³

et al. 2022

Journal of Food and Drug Analysis

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Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing of compounds against Leishmania amastigotes and selected the most promising active compounds, Lansoprazole and Posaconazole. We identified possible Leishmania drug targets of Lansoprazole and Posaconazole using several available servers. Our in-silico screen identified likely Lansoprazole targets as the closely related calcium-transporting ATPases (LdBPK_352080.1, LdBPK_040010.1, and LdBPK_170660.1), and the Posaconazole target as lanosterol 14-alpha-demethylase (LdBPK_111100.1). Further validation showed LdBPK_352080.1 to be the most plausible target based on induced-fit docking followed by long (100ns) MD simulations to confirm the stability of the docked complexes. We present a likely ion channel-based mechanism of action of Lansoprazole against Leishmania calcium-transporting ATPases, which are essential for parasite metabolism and infectivity. The LdBPK_111100.1 interaction with Posaconazole is very similar to the known fungal orthologue. Herein, we present two novel anti-leishmanial agents, Posaconazole and Lansoprazole, already approved by the FDA for different indications and propose plausible mechanisms of action for their antileishmanial activity.

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“…These drugs are all toxic, present with numerous adverse effects, and are expensive. [ 9 ] Therefore, this accentuates the need for new safe and cost‐effective antileishmanial drugs.…”

Section: Introductionmentioning

confidence: 99%

Exploration of ethylene glycol linked nitrofurantoin derivatives against Leishmania: Synthesis and in vitro activity

Ndlovu

Kannigadu

Aucamp

et al. 2023

Archiv der Pharmazie

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Leishmaniasis is a neglected tropical disease that is caused by the Leishmania parasite.It is estimated that there are more than 350 million people at risk of infection annually.Current treatments that are in clinical use are expensive, have toxic side effects, and are facing parasitic resistance. Therefore, new drugs are urgently required. In the quest for new, safe, and cost-effective drugs, a series of novel ethylene glycol derivatives of nitrofurantoin was synthesised and the in vitro antileishmanial efficacy of the compounds tested against Leishmania donovani and Leishmania major strains. Arylated ethylene glycol derivatives were found to be the most potent, with submicromolar activity up to 294-fold greater than the parent compound nitrofurantoin. Analogues 2j and 2k had the best antipromastigote activities with submicromolar IC 50 values against L. major IR-173 and antimonial-resistant L. donovani 9515 strains.

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Amphotericin B-loaded deformable lipid vesicles for topical treatment of cutaneous leishmaniasis skin lesions

Cited by 7 publications

References 47 publications

Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations

Liposomal Amphotericin B for Treatment of Leishmaniasis: From the Identification of Critical Physicochemical Attributes to the Design of Effective Topical and Oral Formulations

Repurposing Lansoprazole and Posaconazole to treat Leishmaniasis: Integration of in vitro testing, pharmacological corroboration, and mechanisms of action

Exploration of ethylene glycol linked nitrofurantoin derivatives against Leishmania: Synthesis and in vitro activity

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