Therapeutic evaluation of free and liposome-encapsulated atovaquone in the treatment of murine leishmaniasis

Cauchetier, E.; Paul, Muriel; Rivollet, D.; Fessi, Hatem; Astier, A.; Deniau, M.

doi:10.1016/s0020-7519(00)00053-9

Cited by 34 publications

(8 citation statements)

References 17 publications

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“…In this case, nanocapsules were produced by interfacial deposition and the encapsulation efficiency was slightly higher than those reported here for PVM/MA nanoparticles (about 97% vs 80-87%). In any case, these encapsulation efficiencies in nanoparticles were higher than those reported for liposomes (Cauchetier et al 2000).…”

Section: Discussioncontrasting

confidence: 63%

“…Other possibilities to increase the atovaquone oral bioavailability have been proposed, including the development of nanosuspensions (Dearn 2000;Nicolaides et al 1999), self-microemulsifying drug delivery systems (Sek et al 2008), liposomes (Cauchetier et al 2000) or polymer nanocapsules (Dalençon et al 1997;Sordet et al 1998;Cauchetier et al 2002). All of these strategies are based on an increment of the specific surface area of the atovaquone particles and/or its solubility in adequate solvents or micelles to facilitate its dispersion in aqueous media.…”

Section: Discussionmentioning

confidence: 99%

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Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Calvo

Lavandera

Agüeros

et al. 2011

Biomed Microdevices

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The aim was to study the ability of bioadhesive cyclodextrin-poly(anhydride) nanoparticles as carriers for the oral delivery of atovaquone (ATO). In order to increase the loading capacity of ATO by poly(anhydride) nanoparticles, the following oligosaccharides were assayed: 2-hydroxypropyl--cyclodextrin (HPCD), 2,6-di-O-methyl-β-cyclodextrin (DCMD), randomly methylated-β-cyclodextrin (RMCD) and sulfobuthyl ether-β-cyclodextrin (SBECD).Nanoparticles were obtained by desolvation after the incubation between the poly(anhydride) with the ATO-cyclodextrin complexes. For the pharmacokinetic studies, ATO formulations were administered orally in rats. Overall, ATO displayed a higher affinity for methylated cyclodextrins than for the other derivatives. However, for in vivo studies, both ATO-DMCD-NP and ATO-HPCD-NP were chosen. These nanoparticle formulations showed more adequate physicochemical properties in terms of size (< 260 nm), drug loading (17.8 and 16.9 g/mg, respectively) and yield (>75%). In vivo, nanoparticle formulations induced higher and more prolonged plasmatic levels of atovaquone than control suspensions of the drug in methylcellulose. Relative bioavailability of ATO when loaded in nanoparticles ranged from 52% (for ATO-HPCD NP) to 71% (for ATO-DMCD NP), whereas for the suspension control formulation the bioavailability was only about 30%. The encapsulation of atovaquone in cyclodextrinspoly(anhydride) nanoparticles seems to be an interesting strategy to improve the oral bioavailability of this lipophilic drug.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Calvo

Lavandera

Agüeros

et al. 2011

Biomed Microdevices

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“…In addition to Sb (32), paromomycin (aminosidine) (186), atovaquone (35), and IFN-␥ (59, 78), which are agents currently in use or previously studied as free drug in human kala-azar (123), have been tested in encapsulated form. Liposomes have also been used to deliver other drugs alone (89,98,105) or in combination (59,78).…”

Section: Experimental Treatment Approachesmentioning

confidence: 99%

Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis

Murray

2001

Antimicrob Agents Chemother

203

184

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“…In the proper formulations and at the appropriate sizes, liposomes deliver drugs to the skin on the basis of the similarity of the bilayer structure of the lipid vesicles to that of the natural membrane and target the macrophages within the dermis (6, 7, 41). Several lipidbased formulations for the treatment of experimental leishmaniasis have been developed (11,19,40,45). …”

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confidence: 99%

Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB/c Mice

Jaafari

Bavarsad

Bazzaz

et al. 2009

Antimicrob Agents Chemother

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The aim of this study was to evaluate the antileishmanial effects of topical liposomal paromomycin sulfate (PM) in Leishmania major-infected BALB/c mice. Liposomes containing 10 or 15% PM (Lip-PM-10 and Lip-PM-15, respectively) were prepared by the fusion method and were characterized for their size and encapsulation efficiency. The penetration of PM from the liposomal PM formulations (LPMFs) through and into skin was evaluated in vitro with Franz diffusion cells fitted with mouse skin at 37°C for 8 h. The in vitro permeation data showed that almost 15% of the LPMFs applied penetrated the mouse skin, and the amount retained in the skin was about 60% for both formulations. The 50% effective doses of Lip-PM-10 and Lip-PM-15 against L. major promastigotes in culture were 65.32 and 59.73 g/ml, respectively, and those against L. major amastigotes in macrophages were 24.64 and 26.44 g/ml, respectively. Lip-PM-10 or Lip-PM-15 was used topically twice a day for 4 weeks to treat L. major lesions on BALB/c mice, and the results showed a significantly (P < 0.001) smaller lesion size in the mice in the treated groups than in the mice in the control group, which received either empty liposomes or phosphate-buffered saline (PBS). Eight weeks after the beginning of the treatment, every mouse treated with LPMFs was completely cured. The spleen parasite burden was significantly (P < 0.001) lower in mice treated with Lip-PM-10 or Lip-PM-15 than in mice treated with PBS or control liposomes, but no significant difference was seen between the two groups treated with either Lip-PM-10 or Lip-PM-15. The results suggest that topical liposomal PM may be useful for the treatment of cutaneous leishmaniasis.Leishmaniasis, which has diverse clinical manifestations, is caused by different species of Leishmania and is endemic in many countries (49). Although cutaneous leishmaniasis (CL) is a self-healing disease, healing takes a long time, and healing times of even up to 2 years have been reported (37). Pentavalent antimonials, which are still the first-line treatment for CL, require multiple injections and are painful; as such, they are not tolerated by most of the patients and, moreover, are not always effective. In addition, resistance to pentavalent antimonials has been reported (12,13,33).Paromomycin sulfate (PM) was reported to show anti-Leishmania activity in the 1960s, and since then PM showed promising activity against both CL and visceral leishmaniasis (VL) in clinical trials (13, 31). Recently, the parenteral formulation of PM has been approved for use for the treatment of VL (27). Nevertheless, the systemic use of PM might cause nephrotoxicity. The conventional topical dosage forms of PM have been tested in clinical trials for their activities against CL and showed promising results, but acceptable efficacy was not always seen (2,3,5,13,18,23,28,43). The formidable barrier nature of the stratum corneum (SC) of the skin does not allow the penetration of drugs with high hydrophilicities and molecular weights, like PM (19). Furthermo...

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Therapeutic evaluation of free and liposome-encapsulated atovaquone in the treatment of murine leishmaniasis

Cited by 34 publications

References 17 publications

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Cyclodextrin/poly(anhydride) nanoparticles as drug carriers for the oral delivery of atovaquone

Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis

Effect of Topical Liposomes Containing Paromomycin Sulfate in the Course of Leishmania major Infection in Susceptible BALB/c Mice

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