Artemisinin and artemisinin plus curcumin liposomal formulations: Enhanced antimalarial efficacy against Plasmodium berghei-infected mice

Isacchi, Benedetta; Bergonzi, Maria Camilla; Grazioso, Margherita; Righeschi, Chiara; Pietretti, A; Severini, Carlo; Bilia, Anna Rita

doi:10.1016/j.ejpb.2011.11.015

Cited by 111 publications

(67 citation statements)

References 21 publications

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“…26,27 DNC was kept at 4°C±1°C, and at fixed time intervals they were assayed for their physical and chemical stability. Physical stability was checked by monitoring the size and PDI using DLS measurements.…”

Section: Stability Studiesmentioning

confidence: 99%

Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells

Mirgani¹,

Isacchi²,

Sadeghizadeh³

et al. 2014

IJN

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Glioblastoma is an invasive tumor of the central nervous system. Tumor recurrence resulting from ineffective current treatments, mainly due to the blood–brain barrier, highlights the need for innovative therapeutic alternatives. The recent availability of nanotechnology represents a novel targeted strategy in cancer therapy. Natural products have received considerable attention for cancer therapy because of general lower side effects. Curcumin is a new candidate for anticancer treatment, but its low bioavailability and water solubility represent the main disadvantages of its use. Here, curcumin was efficiently encapsulated in a nontoxic nanocarrier, termed dendrosome, to overcome these problems. Dendrosomal curcumin was prepared as 142 nm spherical structures with constant physical and chemical stability. The inhibitory role of dendrosomal curcumin on the proliferation of U87MG cells, a cellular model of glioblastoma, was evaluated by considering master genes of pluripotency and regulatory miRNA (microribonucleic acid). Methylthiazol tetrazolium assay and flow cytometry were used to detect the antiproliferative effects of dendrosomal curcumin. Annexin-V-FLUOS and caspase assay were used to quantify apoptosis. Real-time polymerase chain reaction was used to analyze the expression of OCT4 (octamer binding protein 4) gene variants ( OCT4A , OCT4B , and OCT4B1 ), SOX-2 (SRY [sex determining region Y]-box 2) , Nanog , and miR-145 . Dendrosomal curcumin efficiently suppresses U87MG cells growth with no cytotoxicity related to dendrosome. Additionally, the accumulation of cells in the SubG 1 phase was observed in a time- and dose-dependent manner as well as higher rates of apoptosis after dendrosomal curcumin treatment. Conversely, nonneoplastic cells were not affected by this formulation. Dendrosomal curcumin significantly decreased the relative expression of OCT4A , OCT4B1 , SOX-2 , and Nanog along with noticeable overexpression of miR-145 as the upstream regulator. This suggests that dendrosomal curcumin reduces the proliferation of U87MG cells through the downregulation of OCT4 (octamer binding protein 4) variants and SOX-2 (SRY [sex determining region Y]-box 2) in an miR-145 -dependent manner.

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Section: Stability Studiesmentioning

confidence: 99%

Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells

Mirgani¹,

Isacchi²,

Sadeghizadeh³

et al. 2014

IJN

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“…Formulations involving liposomes and self-emulsifying drug delivery systems enhance the efficacy of anti-infective agents, including antimalarial drugs, such as artemisinins (16)(17)(18)(19). A Pheroid delivery system has been shown to increase the in vitro antimalarial activities of azithromycin, mefloquine, and quinine significantly (20,21).…”

mentioning

confidence: 99%

“…A plausible explanation for recrudescence is drug-induced quiescence or dormancy that protects ring-stage parasites against artemisinin exposure (9, 10). The artemisinin-treated ring stages of P. falciparum thereby enter a temporary growth arrest (11, 12), wherein they survive drug treatment, resuming normal growth once drug pressure is removed (13-15).Formulations involving liposomes and self-emulsifying drug delivery systems enhance the efficacy of anti-infective agents, including antimalarial drugs, such as artemisinins (16)(17)(18)(19). A Pheroid delivery system has been shown to increase the in vitro antimalarial activities of azithromycin, mefloquine, and quinine significantly (20,21).…”

mentioning

confidence: 99%

Assessment of the Induction of Dormant Ring Stages in Plasmodium falciparum Parasites by Artemisone and Artemisone Entrapped in Pheroid Vesicles In Vitro

Grobler

Chavchich²,

Haynes

et al. 2014

Antimicrob Agents Chemother

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cThe in vitro antimalarial activities of artemisone and artemisone entrapped in Pheroid vesicles were compared, as was their ability to induce dormancy in Plasmodium falciparum. There was no increase in the activity of artemisone entrapped in Pheroid vesicles against multidrug-resistant P. falciparum lines. Artemisone induced the formation of dormant ring stages similar to dihydroartemisinin. Thus, the Pheroid delivery system neither improved the activity of artemisone nor prevented the induction of dormant rings. Since 2006, artemisinin-based combination treatment (ACT) has been the cornerstone of malaria chemotherapy (1). However, high treatment failure rates with artesunate-mefloquine (AS-MQ) (2) and dihydroartemisinin (DHA)-piperaquine (3) in western Cambodia highlight the urgent need for effective ACTs until more potent replacement drugs can be developed.Although artemisinin and its derivatives are the most potent and rapidly acting drugs for the treatment of Plasmodium falciparum malaria (4), this drug class is associated with high recrudescence. Artemisone (AMS), a new derivative, has potent antiplasmodial activity, good oral bioavailability, and metabolic stability (5) and is well tolerated in humans (6), with an effective curative dose approximately one-third that of artesunate (7). However, use of artemisone alone, as with the other artemisinins, also leads to recrudescence in nonhuman primates (8). A plausible explanation for recrudescence is drug-induced quiescence or dormancy that protects ring-stage parasites against artemisinin exposure (9, 10). The artemisinin-treated ring stages of P. falciparum thereby enter a temporary growth arrest (11, 12), wherein they survive drug treatment, resuming normal growth once drug pressure is removed (13-15).Formulations involving liposomes and self-emulsifying drug delivery systems enhance the efficacy of anti-infective agents, including antimalarial drugs, such as artemisinins (16)(17)(18)(19). A Pheroid delivery system has been shown to increase the in vitro antimalarial activities of azithromycin, mefloquine, and quinine significantly (20,21). Entrapment of artemisone in Pheroid vesicles also has been shown to enhance blood artemisone concentrations in mice (22) and primates (23). We investigated the effect of a Pheroid formulation on the antimalarial activity of artemisone and on dormancy in vitro. If this formulation prevents the induction of dormancy in vitro, it may circumvent recrudescences occurring following artemisinin treatment.Chloroquine diphosphate (CQ) and MQ (Sigma-Aldrich, St. Louis, MO), atovaquone (ATQ) (GlaxoSmithKline, Middlesex, United Kingdom), DHA, and AS (DK Pharma, Hanoi, Vietnam) were used. Artemisone and its metabolite M1 were obtained from the Hong Kong University of Science and Technology. The active M1 metabolite is formed via dehydrogenation in the thiomorpholine-dioxide moiety of artemisone (5, 6). The artemisone-entrapped Pheroid vesicles (AMS-Phe) were prepared by adding 30 mM artemisone to a pro-Pheroid formulation (i.e., oil...

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“…9,10 The other strategy is the development and use of novel drug delivery systems in order to improve the efficacy, specificity, tolerability and therapeutic index of existing antimalarial drugs. [11][12][13] In recent years, some antibiotics have been studied for their antimalarial properties and are generally combined with antimalarials in an effort to overcome the global challenge of drug-resistant P. falciparum. 14 Antibiotics, including tetracyclines, quinolines, macrolides and rifampin, have proved antimalarial action in vitro.…”

Section: Introductionmentioning

confidence: 99%

In vitro activity of Pheroid vesicles containing antibiotics against Plasmodium falciparum

et al. 2012

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The macrolide antibiotics, erythromycin and azithromycin, have been studied for their potential antimalarial activity, but only modest activity has been demonstrated. In this study, we investigated the enhancement of the efficacy of these antibiotics in combination with a patented lipid-based drug delivery system, Pheroid technology. A chloroquine resistant strain of Plasmodium falciparum (RSA11) was incubated with the formulations for a prolonged incubation time (144 h). Drug efficacy assays were conducted by analyzing the histidine-rich protein II levels of the parasites. The effects of azithromycin and erythromycin were compared with other antibiotics and standard antimalarial drugs. The poor water soluble nature of the drugs led to the formation of micro scale Pheroid vesicles with average particle sizes of 72.76±10.73 lm for azithromycin and 100.62±29.27 lm for erythromycin. The IC 50 values of erythromycin and azithromycin alone and entrapped in Pheroid vesicles decreased statistically significant (Pp0.05). Prolonged exposure was also statistically meaningful (Pp0.05), although it seems that exposure need not exceed 96 h. Pheroid vesicles also proved successful in decreasing the IC 50 values of doxycycline, tetracycline and triclosan. Pheroid vesicles containing antibiotics could prove successful as a malaria treatment option.

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Artemisinin and artemisinin plus curcumin liposomal formulations: Enhanced antimalarial efficacy against Plasmodium berghei-infected mice

Cited by 111 publications

References 21 publications

Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells

Dendrosomal curcumin nanoformulation downregulates pluripotency genes via miR-145 activation in U87MG glioblastoma cells

Assessment of the Induction of Dormant Ring Stages in Plasmodium falciparum Parasites by Artemisone and Artemisone Entrapped in Pheroid Vesicles In Vitro

In vitro activity of Pheroid vesicles containing antibiotics against Plasmodium falciparum

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