- Economic impact of treating invasive mold disease with isavuconazole compared with liposomal amphotericin B in the UK. [Journal Article]
- FMFuture Microbiol 2018 06 18
- CONCLUSIONS: ISAV has the potential to reduce IMD treatment costs relative to L-AMB followed by POSA.
- Macrophage Activation Marker Neopterin: A Candidate Biomarker for Treatment Response and Relapse in Visceral Leishmaniasis. [Journal Article]
- FCFront Cell Infect Microbiol 2018; 8:181
- The Leishmania parasite resides and replicates within host macrophages during visceral leishmaniasis (VL). This study aimed to evaluate neopterin, a marker of macrophage activation, as possible pharm...
The Leishmania parasite resides and replicates within host macrophages during visceral leishmaniasis (VL). This study aimed to evaluate neopterin, a marker of macrophage activation, as possible pharmacodynamic biomarker to monitor VL treatment response and to predict long-term clinical relapse of VL. Following informed consent, 497 plasma samples were collected from East-African VL patients receiving a 28-day miltefosine monotherapy (48 patients) or 11-day combination therapy of miltefosine and liposomal amphotericin B (L-AMB, 48 patients). Neopterin was quantified with ELISA. Values are reported as median (inter-quartile range). Baseline neopterin concentrations were elevated in all VL patients at 98.8 (63.9-135) nmol/L compared to reported levels for healthy controls (<10 nmol/L). During the first treatment week, concentrations remained stable in monotherapy patients (p = 0.807), but decreased two-fold compared to baseline in the combination therapy patients (p < 0.01). In the combination therapy arm, neopterin concentrations increased significantly 1 day after L-AMB infusion compared to baseline for cured patients [137 (98.5-197) nmol/L, p < 0.01], but not for relapsing patients [84.4 (68.9-106) nmol/L, p = 0.96]. The neopterin parameter with the highest predictive power for VL relapse was a higher than 8% neopterin concentration increase between end of treatment and day 60 follow-up (ROC AUC 0.84), with a 93% sensitivity and 65% specificity. In conclusion, the identified neopterin parameter could be a potentially useful surrogate endpoint to identify patients in clinical trials at risk of relapse earlier during follow-up, possibly in a panel of biomarkers to increase its specificity.
- Enrichment of liposomal nanomedicines using monolithic solid phase extraction discs following preactivation with bivalent metal ion solutions. [Journal Article]
- JCJ Chromatogr A 2018 Jun 05
- Silicate is an excellent adsorbent because of its large surface area and amenability to surface modification. In this study, the representative liposome nanomedicines DOXIL® and AmBisome® were enrich...
Silicate is an excellent adsorbent because of its large surface area and amenability to surface modification. In this study, the representative liposome nanomedicines DOXIL® and AmBisome® were enriched using a silica monolith disc (diameter 4.2 mm, length 1.5 mm) with bimodal pores. Although the nanoparticles passed through the disc without retention when water was used as the preactivation solution, they were strongly retained by the disc when a 1 M bivalent metal (such as Mg2+, Ca2+, and Ni2+) solution was used. Notably, strong affinity was observed to DOXIL, a pegylated liposomal nanoparticle, by the disc composed of 5 μm and 10 nm through- and meso pores, respectively, and nearly 100% of DOXIL was recovered from a 40× diluted solution. Overall, the results demonstrate that monolithic discs are effective for the enrichment of liposomal nanomedicines.
- Bioanalysis of free and liposomal Amphotericin B in rat plasma using solid phase extraction and protein precipitation followed by LC-MS/MS. [Journal Article]
- JPJ Pharm Biomed Anal 2018 Jun 08; 158:288-293
- Amphotericin B (AMB) is a polyene macrolide antibiotic used for treating invasive fungal infections. Liposomal AMB (L-AMB) is a lipid dosage form which reduces the side effects and toxicity of the dr...
Amphotericin B (AMB) is a polyene macrolide antibiotic used for treating invasive fungal infections. Liposomal AMB (L-AMB) is a lipid dosage form which reduces the side effects and toxicity of the drug. The quantitation of free AMB (F-AMB) and L-AMB in vivo is important to monitor quality control of the liposomal formulation and to ensure its safety during clinical use. In this study, an original strategy was developed to separately determine F-AMB and L-AMB in rat plasma using LC-MS/MS. F-AMB was analyzed after separation by solid phase extraction, total AMB (T-AMB) was determined after protein precipitation and L-AMB was determined by difference. The method was fully validated. Calibration curves were linear in the ranges 0.7-120 μg/mL for T-AMB and 0.2-20 μg/mL for F-AMB. Accuracy and precision results were within acceptable variability limits, recoveries were consistent and reproducible, matrix effects were insignificant and analytes were stable under all the storage conditions tested. The method was successfully applied to a pharmacokinetic study in rats administered a single intravenous 6 mg/kg dose of L-AMB. The method will allow further clinical studies of L-AMB and provide useful technical support for the assay of other liposomal drug formulations.
- COMPARATIVE EFFECTIVENESS AND SAFETY BETWEEN AMPHOTERICIN B LIPID-FORMULATIONS: A SYSTEMATIC REVIEW. [Journal Article]
- IJInt J Technol Assess Health Care 2018 Jun 13; :1-9
- CONCLUSIONS: The studies included in this systematic review pointed toward less nephrotoxicity events in the L-AmB group. However, due to low quality of evidence and no statistically significant differences in other clinical relevant outcomes, there is no definitive evidence of overall superiority in effectiveness or safety outcomes regarding one lipid formulation or another in this population subgroup.
- Cost-effectiveness of amphotericin B formulations in the treatment of systemic fungal infections. [Journal Article]
- MMycoses 2018 Jun 12
- CONCLUSIONS: CAB is the most cost-effective treatment, followed by LAB and ABLC. Although CAB presents critical safety aspects, the high acquisition costs of the other formulations prevent their large-scale use in Brazil. This article is protected by copyright. All rights reserved.
- Epidemiological, clinical and laboratory aspects of human visceral leishmaniasis (HVL) associated with human immunodeficiency virus (HIV) coinfection: a systematic review. [Journal Article]
- PParasitology 2018 May 28; :1-18
- Coinfection with human visceral leishmaniasis (HVL) and human immunodeficiency virus (HIV) has become an emerging public health problem in several parts of the world, with high morbidity and mortalit...
Coinfection with human visceral leishmaniasis (HVL) and human immunodeficiency virus (HIV) has become an emerging public health problem in several parts of the world, with high morbidity and mortality rates. A systematic review was carried out in the literature available in PubMed, Scielo and Lilacs related to HVL associated with HIV coinfection, seeking to analyze epidemiological, clinical and laboratory aspects. Of the 265 articles found, 15 articles were included in the qualitative analysis, which referred to the results of HVL treatment in patients coinfected with HIV. In the published articles between 2007 and 2015, 1171 cases of HVL/HIV coinfection were identified, 86% males, average age 34 years, liposomal amphotericin B was the most commonly used drug, cure rates 68 and 20% relapses and 19% deaths, five different countries, bone marrow was used in 10/15 manuscripts. HVL/HIV coinfection is a major challenge for public health, mainly due to the difficulty in establishing an accurate diagnosis, low response to treatment with high relapse rates and evolution to death. In addition, these two pathogens act concomitantly for the depletion of the immune system, contributing to worsening the clinical picture of these diseases, which requires effective surveillance and epidemiological control measures.
- The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study. [Journal Article]
- PNPLoS Negl Trop Dis 2018; 12(5):e0006527
- CONCLUSIONS: Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in clinical trials.
- Epidemiological and clinical features of visceral leishmaniasis in children in Alicante Province, Spain. [Journal Article]
- PIPaediatr Int Child Health 2018 May 23; :1-6
- Background Visceral leishmaniasis (VL) is endemic to the Mediterranean basin. In children, VL often presents with non-specific symptoms and can be life-threatening without proper treatment. Aim To de...
Background Visceral leishmaniasis (VL) is endemic to the Mediterranean basin. In children, VL often presents with non-specific symptoms and can be life-threatening without proper treatment. Aim To describe the epidemiological and clinical features of pediatric VL in children in Alicante, Spain. Methods The study included all paediatric (<15 years) cases admitted to three hospitals in the province of Alicante from May 1992 to May 2015 with diagnosis of VL (detection was either by anti-Leishmania antibodies in serology or Leishmania in blood and/or bone marrow aspirates). Results There were 38 cases of pediatric VL (18 aged <24 months, 15 aged 24-59 months and 5 aged ≥5 years). The main symptoms were fever (97.4%), followed by pallor (75.0%) and loss of appetite (46.4%). Eighty-seven per cent of patients were anaemic (haemoglobin < 9 g/dL), 73.7% had neutropenia and 68.4% had thrombocytopenia. Before 2004, 92.3% of patients were treated with meglumine antimoniate (MA) and 7.7% with liposomal amphotericin B (LAmB); after 2004, 84% were treated with LAmB and just one (16%) with MA (p < 0.001). LAmB performed better than MA in terms of mean treatment length (7.4 days vs 25.9 days, p < 0.001), time to becoming afebrile (1.7 vs 13.7 days, p < 0.001), and length of hospital stay (10.9 vs 19.4 days, p = 0.001). Conclusion Paediatric VL in Alicante mainly affects children under five. Children aged ≤24 months present with a lower haemoglobin and white blood cell count. Treatment with LAmB reduces treatment length, time to becoming afebrile and length of hospital stay.
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- Lactoferrin-modified Betulinic Acid-loaded PLGA nanoparticles are strong anti-leishmanials. [Journal Article]
- CCytokine 2018 May 18
- Visceral Leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani, is a potentially fatal disease. The only orally bioavailable drug miltefosine is toxic and the effective liposomal A...
Visceral Leishmaniasis (VL), caused by the protozoan parasite Leishmania donovani, is a potentially fatal disease. The only orally bioavailable drug miltefosine is toxic and the effective liposomal Amphotericin B (AmBisome) is limited by its prohibitive cost and requirement for parenteral administration. Therefore, finding a new potential drug candidate and an alternative delivery system is imperative. We report that Betulinic acid (BA), a pentacyclic triterpenoid from Betula alba bark, was loaded onto uniformly spherical PLGA nanoparticles (BANPs; diameter 187.5 ± 5.60 nm) coated with Lactoferrin (Lf-BANPs). The amastigotes count in macrophages was more effectively reduced by Lf-BANP than BA and BANP. Lf-BANPs reduced the pro-parasitic, anti-inflammatory cytokine IL-10, but increased nitric oxide (NO), production in L. donovani-infected macrophages indicating that Lf-BANP possesses a significant anti-leishmanial activity.