Unsweetened Natural Cocoa Powder: A Potent Nutraceutical in Perspective

Unsweetened natural cocoa powder is a pulverized high-grade powder of compressed solid blocks which remains after extraction and removal of the cocoa butter. The authors determined the elementary composition of UNCP, investigated its effect on nitric oxide levels, toxicity, and its protective effect on the heart, kidney, and liver during simultaneous administration with high dose (HD) artemether/lumefantrine (A/L). Macro- and microelements in UNCP were analyzed with energy dispersive x-ray fluorescence spectroscopy (EDXRF). Adult male guinea pigs were administered various doses of UNCP alone and also simultaneously with A/L. Phytochemical analysis of UNCP showed the presence of saponins, flavonoids, tannins, cardiac glycosides, and 38 macro- and microelements. Histopathological analysis showed no toxic effect on the heart, liver, kidney, lungs, testis, and spleen. Administration of various doses of UNCP increased white blood cell counts and lymphocyte count (p > 0.05) compared with the controls. Additionally, UNCP and A/L combination caused an increase in nitric oxide levels when compared with the control group and restores some hematological disorders induced by the 3-day HD A/L administration. Even though UNCP appears to be relatively safe, care should be taken due to the high content of copper element to avoid the possibility of intestinal lining erosion

Quinine Sulphate Microparticles as Treatment for Leishmaniasis

Background. Leishmaniasis is a neglected tropical disease caused by the Leishmania parasite and transmitted by the female phlebotomine sandfly. The disease can affect the skin (least fatal) or internal organs (most fatal). Current treatment options for leishmaniasis have a number of adverse effects, and there appears to be resistance by the protozoan parasite (Leishmania spp.). Reports suggest that quinine sulphate, not indicated for leishmaniasis, is effective in killing the Leishmania parasite. Indeed, the efficacy of any drug is dependent on the concentration at the target site, which is also almost dependent on drug formulation. The current study assessed the pharmacokinetic profile of the microparticulate formulation of quinine sulphate and its in vitro and in vivo efficacy against Leishmania donovani. Methods. Quinine sulphate was encapsulated in bovine serum albumin by the spray-drying method. Quinine sulphate microparticles were evaluated for size, zeta potential, drug content, encapsulation efficiency, and in vitro release properties. Afterwards, the pharmacokinetic characteristics of quinine sulphate microparticles were estimated and in vivo efficacy studies were also conducted. Results. The size range of the quinine sulphate microparticles was between 2.0 and 5.0 µm. Microparticles had an average zeta potential of −35.2 mV and an encapsulation efficiency of 94.5%. Also, Cmax, t1/2, and AUC were all significantly desirable for quinine sulphate microparticles compared to the drug powder. Quinine sulphate microparticles significantly reduced parasite load in rat organs than amphotericin B. Conclusion. Overall, quinine sulphate microparticles had better pharmacokinetic profile and showed higher efficacy against Leishmania donovani parasites in vivo. Thus, quinine sulphate microparticles have the potential, especially, in treating visceral leishmaniasis

Transdermal Vaccination with the Matrix-2 Protein Virus-like Particle (M2e VLP) Induces Immunity in Mice against Influenza A Virus

In this study, our goal was to utilize the extracellular domain matrix-2 protein virus-like particle (M2e VLP) that has been found to be highly conserved amongst all strains of influenza and could serve as a potential vaccine candidate against influenza. Previous studies have demonstrated that the VLP of the M2e showed increased activation of innate and adaptive immune responses. Therefore, to further explore its level of efficacy and protection, this vaccine was administered transdermally and tested in a pre-clinical mouse model. The M2e VLP was encapsulated into a polymeric matrix with the addition of Alhydrogel® and Monophosphoryl Lipid-A (MPL-A®), together referred to as AS04. The M2e VLP formulations induced IgG titers, with increased levels of IgG1 in the M2e VLP MP groups and further elevated levels of IgG2a were found specifically in the M2e VLP MP Adjuvant group. This trend in humoral immunity was also observed from a cell-mediated standpoint, where M2e VLP MP groups showed increased expression in CD4+ T cells in the spleen and the lymph node and high levels of CD8+ T cells in the lymph node. Taken together, the results illustrate the immunogenic potential of the matrix-2 protein virus-like particle (M2e VLP) vaccine

Transdermal Immunization with Microparticulate RSV-F Virus-like Particles Elicits Robust Immunity

No approved vaccines against respiratory syncytial virus (RSV) infections exist to date, due to challenges arising during vaccine development. There is an unmet need to explore novel approaches and a universal strategy to prevent RSV infections. Previous studies have proven the immune efficacy of virus-like particles (VLPs) consisting of RSV fusion (F) protein, yielding a highly immunogenic RSV-F VLP subunit vaccine. In this study, RSV-F VLP (with or without MPL®) was added to a polymer mix and spray-dried, forming microparticles. The formulations were transdermally administered in C57BL/6 mice to evaluate vaccine efficacy. The transdermal delivery of RSV-F VLP + MPL® was more effective in clearing lung viral loads and preventing weight loss after RSV challenge. At the cellular level, MPL® augmented the vaccine response in microparticulate form, which was evidenced by higher serum and lung antibody titers, and lower lung viral titers in the vaccinated groups. These preliminary results validate the effectiveness of the RSV-F VLP microparticulate vaccine via the transdermal route due to its potential to trigger robust immune responses

Transdermal Immunization with Microparticulate RSV-F Virus-like Particles Elicits Robust Immunity

No approved vaccines against respiratory syncytial virus (RSV) infections exist to date, due to challenges arising during vaccine development. There is an unmet need to explore novel approaches and a universal strategy to prevent RSV infections. Previous studies have proven the immune efficacy of virus-like particles (VLPs) consisting of RSV fusion (F) protein, yielding a highly immunogenic RSV-F VLP subunit vaccine. In this study, RSV-F VLP (with or without MPL®) was added to a polymer mix and spray-dried, forming microparticles. The formulations were transdermally administered in C57BL/6 mice to evaluate vaccine efficacy. The transdermal delivery of RSV-F VLP + MPL® was more effective in clearing lung viral loads and preventing weight loss after RSV challenge. At the cellular level, MPL® augmented the vaccine response in microparticulate form, which was evidenced by higher serum and lung antibody titers, and lower lung viral titers in the vaccinated groups. These preliminary results validate the effectiveness of the RSV-F VLP microparticulate vaccine via the transdermal route due to its potential to trigger robust immune responses

Reproductive Toxicity of Theobroma cacao: Increase in Survival Index, Nongenotoxic, and Proimplantation Potential

Unsweetened natural cocoa (UNCP) was evaluated for reproductive toxicity in rats. A preliminary genotoxic potential was evaluated by the DNA comet assay test using C57Bl/6 mice. Both therapeutic dose (TD; 900 mg/kg) and high dose (HD; 9000 mg/kg) of UNCP were used. White Wistar rats were used in two experimental groups. The females received UNCP 15 days before crossing with untreated males. The males received UNCP for 48 days before mating with untreated females. Subacute toxicity was observed during a 14-day oral administration of UNCP. Results show that a high tail DNA% was observed with methyl mesylate administration in all tissues analysed. The lowest tail DNA% value was observed in the liver (1.64 ± 0.26) and kidney (1.63 ± 0.30) during UNCP (TD) administration. UNCP did not induce observable physical congenital malformations on the pubs of treated female and male rats, lacks genotoxic potential, and did not adversely affect pregnancy index, pub weights, and survival index, but UNCP exhibited proimplantation potential (p>0.05)

A combination of unsweetened natural cocoa powder and artemether/lumefantrine: a strategy to improve malaria treatment outcomes

Background: Reports suggest that unsweetened natural cocoa powder (UNCP) has antiplasmodial activity and contains enough fat content to enhance the absorption of artemether/lumefantrine (A/L). Objective: This study assessed the pharmacokinetic and pharmacodynamic properties of UNCP co-administered with A/L. Methods: Male Sprague-Dawley (SD) rats were infected with A/L-sensitive Plasmodium berghei. Rane’s curative model was used to assess the effect of the excipient UNCP (300 - 1500 mg/kg) formulated with A/L on parasite clearance. Additionally, healthy non-malarious male SD rats were co-administered orally with the fixed doses of A/L (recommended therapeutic dose of 2 mg/kg artemether and 12 mg/kg lumefantrine) with varying doses of UNCP (300, 600, 900, 1200 and 1500 mg/kg), to assess the effect of UNCP on the disposition of A/L. The number of mice in each group that were given each dose was five (n = 5). Plasma lumefantrine concentration was assayed using HPLC/UV-Vis. Results: Co-administration of UNCP (1200 and 1500 mg/kg) with A/L caused a significant difference in parasite clearance compared to conventional A/L (Coartem®-only) or UNCP alone. Pharmacokinetic analysis showed that the peak serum concentration (Cmax) of lumefantrine for the A/L+UNCP (1200 mg/kg and 1500 mg/kg) was higher than the Coartem®-only group. Additionally, the area under the lumefantrine concentration-time curve (AUC0→24) post-drug administration was higher for the A/L+UNCP (1200 mg/kg and 1500 mg/kg) groups compared to the commercially obtained conventional A/L Coartem®-only group. Conclusion: UNCP, co-administered with A/L, increased the in vivo antiplasmodial activity of A/L enhanced lumefantrine disposition (peak concentration and total drug exposure) in rats. Thus, it can be exploited as an excipient in the formulation of A/L for the management of uncomplicated malaria in humans