Strategies for the design of orally bioavailable antileishmanial treatments

Pham, Thi-Minh-Hue; Loiseau, Philippe M.; Barratt, Gillian

doi:10.1016/j.ijpharm.2013.07.035

Cited by 54 publications

(38 citation statements)

References 208 publications

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“…Recently, novel drug delivery systems including liposomes, niosomes, microspheres, nanoparticles, and carbon nanotubes (CNTs) have been used to provide targeted delivery of the drug to macrophages [Pham et al 2013]. The lipid formulations have excellent efficacy and are less toxic but cost is a limiting factor.…”

Section: New Amb Formulationsmentioning

confidence: 99%

Recent developments and future prospects in the treatment of visceral leishmaniasis

Sundar

Singh

2016

Therapeutic Advances in Infection

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Limited therapeutic options in visceral leishmaniasis (VL) make the treatment of this neglected disease very challenging. In addition to this, long treatment duration and toxic adverse effects make it even more difficult. With no effective vaccine available to date, treatment of VL is based only on chemotherapy. In the Indian subcontinent, a single dose of liposomal amphotericin B (L-AmB) and multidrug therapy (L-AmB þ miltefosine, LAmB þ paromomycin [PM], or miltefosine þ PM) are the treatments of choice for VL. In East Africa, however, combination therapy of pentavalent antimonials (Sb v ) and PM remains the treatment of choice, and in the Mediterranean region and South America, L-AmB is the recommended drug. Fexinidazole and PA-824 are new promising drugs which have shown encouraging results in preclinical studies.

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Section: New Amb Formulationsmentioning

confidence: 99%

Recent developments and future prospects in the treatment of visceral leishmaniasis

Sundar

Singh

2016

Therapeutic Advances in Infection

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“…In recent years, improvements in the oral delivery of AmB have been sought by using different formulations, such as lipid-based cochleates (Delmas et al, 2002), nanosuspension (Kayser et al, 2003), lipid nanospheres and a self-emulsifying drug delivery system (Pham et al, 2013). The nanoemulsified carrier has shown promise as a carrier system for the oral delivery of poor water soluble and poor membrane permeable drugs.…”

Section: Introductionmentioning

confidence: 99%

“…The nanoemulsified carrier has shown promise as a carrier system for the oral delivery of poor water soluble and poor membrane permeable drugs. It is prepared by mixing a surfactant, co-surfactant, oil and drug that form an oil-in-water emulsion in aqueous medium after homogenization and form nanocarrier below 100 nm which is anticipated to enhance oral bioavailability by different mechanisms (Wu et al, 2006;Pham et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non‐toxic chemotherapy

Gupta

Jaiswal

Asthana

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSEThe aim of this study was to devise a nanoemulsified carrier system (CopNEC) to improve the oral delivery of amphotericin B (AmB) by increasing its oral bioavailability and synergistically enhance its antileishmanial activity with copaiba oil (Cop). EXPERIMENTAL APPROACHThe AmB encapsulated NEC (CopNEC-AmB) comprised of Cop, d-α-tocopheryl polyethylene glycol 1000 succinate and phosphatidylcholine was prepared by high-pressure homogenization method. Stability study of CopNEC-AmB was carried out in simulated gastric fluid and simulated intestinal fluid. The CopNEC-AmB and plain AmB were compared as regards their in vitro antileishmanial activity, pharmacokinetics, organ distribution and toxicity. KEY RESULTSThe optimal CopNEC-AmB had a small globule size, low polydispersity index, high ζ potential and encapsulation efficiency. The high resolution transmission electron microscopy illustrated spherical particle geometry with homogeny in their sizes. The optimal CopNEC-AmB was found to be stable in gastrointestinal fluids showing insignificant changes in globule size and encapsulation efficiency. The AUC0-48 value of CopNEC-AmB in rats was significantly improved showing 7.2-fold higher oral bioavailability than free drug. The in vitro antileishmanial activity of CopNEC-AmB was significantly higher than that of the free drug as Cop synergistically enhanced the antileishmanial effect of AmB by causing drastic changes in the morphology of Leishmania parasite and rupturing its plasma membrane. The CopNEC-AmB showed significantly less haemolytic toxicity and cytotoxicity and did not change the histopathology of kidney tissues as compared with AmB alone. CONCLUSIONS AND IMPLICATIONSThis prototype CopNEC formulation showed improved bioavailability and had a non-toxic synergistic effect on the antileishmanial activity of AmB.

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“…No obstante, su tratamiento continúa siendo basado en el uso de sales de antimonio pentavalente como medicamentos de primera línea, o el uso de la amfotericina B y pentamidina, como medicamentos de segunda línea, los cuales son frecuentemente tóxicos, algunos tienen un modo de acción desconocido, y usualmente son marginalmente efectivos, sumado al agravante que ya hay diversos brotes de resistencia (Arboleda et al, 2013;Sundar y Rai, 2002). A la fecha, no han sido muchos los avances en la sustitución de estos medicamentos, con algunos casos de terapia inciertamente eficaces (Pham et al, 2013), aunque ya existen algunos en ensayos clínicos basados en medicamentos ya conocidos, tales como el allopurinol ® (inhibidor de síntesis de proteínas), el ambisoma ® (una formulación de amfotericina B en liposomas) y el ketaconazol ® (un inhibidor de la sín-tesis de esteroles) (Jebran et al, 2014;Setzer, 2013). Una ruta metabólica que ha sido explotada para el tratamiento de enfermedades parasitarias involucra la biosíntesis de co-factores de tipo folato a través de la inhibición de la dihidrofolato reductasa (DHFR) (Nare et al, 1997).…”

Section: Introductionunclassified

Diterpenos de Núcleo Kaurano como Inhibidores de la PTR1 de Leishmania: un Estudio In-Silico

Díaz

Bernal

Coy-Barrera

2013

Rev. Fac. Cienc. Básicas

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RESUMENLa pteridina reductasa-1 (PTR1) ha sido descubierta como la responsable de la reducción de la susceptibilidad a antifolatos (e.g., metotrexato) de parásitos tripanosómicos, lo cual la ha convertido en un objetivo quimioterapeútico. Por esta razón, trece diterpenos conocidos, de núcleo kaurano, fueron evaluados in silico contra la PTR1, mediante docking molecular y modelamiento farmacofórico. El docking molecular mostró claras interacciones polares con algunos residuos del sitio activo de la PTR1, que dependieron principalmente de la presencia de un grupo carboxilo en C19. Estos resultados fueron corroborados por el mapeo de interacciones residuales, indicando que los ácidos kauren-19-oicos poseen las características estructurales importantes para una inhibición de la PTR1, lo cual es un excelente punto de partida para futuros estudios de optimización estructural de este tipo de compuestos.Palabras clave: Diterpenos, kaurano, in silico, docking molecular.

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Strategies for the design of orally bioavailable antileishmanial treatments

Cited by 54 publications

References 208 publications

Recent developments and future prospects in the treatment of visceral leishmaniasis

Recent developments and future prospects in the treatment of visceral leishmaniasis

Synergistic enhancement of parasiticidal activity of amphotericin B using copaiba oil in nanoemulsified carrier for oral delivery: an approach for non‐toxic chemotherapy

Diterpenos de Núcleo Kaurano como Inhibidores de la PTR1 de Leishmania: un Estudio In-Silico

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