27 research outputs found
Malaria vaccine: a current perspective
No full textThe observation that inactivated Plasmodium sporozoites could protect against malaria is about a hundred years old. However, systematic demonstration of protection using irradiated sporozoites occurred in the nineteen-sixties, providing the impetus for the development of a malaria vaccine. In 1983, the circumsporozoite protein (CSP), a major sporozoite surface antigen, became the first Plasmodium gene to be cloned, and a CSP-based vaccine appeared imminent. Today, 25 years later, we are still without an effective malaria vaccine, despite considerable information regarding the genomics and proteomics of the malaria parasites. Although clinical immunity to malaria has been well-documented in adults living in malaria endemic areas, our understanding of the host-immune responses operating in such malaria immune persons remains poor, and limits the development of immune control of the disease. Currently, several antigen and adjuvant combinations have entered clinical trials, in which efficacy against experimental sporozoite challenge and/or exposure to natural infection is evaluated. This review collates information on the recent status of the field. Unresolved challenges facing the development of a malaria vaccine are also discussed
Malaria vaccine: a current perspective
No full textThe observation that inactivated Plasmodium sporozoites could protect against malaria is about a hundred years old. However, systematic demonstration of protection using irradiated sporozoites occurred in the nineteen-sixties, providing the impetus for the development of a malaria vaccine. In 1983, the circumsporozoite protein (CSP), a major sporozoite surface antigen, became the first Plasmodium gene to be cloned, and a CSP-based vaccine appeared imminent. Today, 25 years later, we are still without an effective malaria vaccine, despite considerable information regarding the genomics and proteomics of the malaria parasites. Although clinical immunity to malaria has been well-documented in adults living in malaria endemic areas, our understanding of the host-immune responses operating in such malaria immune persons remains poor, and limits the development of immune control of the disease. Currently, several antigen and adjuvant combinations have entered clinical trials, in which efficacy against experimental sporozoite challenge and/or exposure to natural infection is evaluated. This review collates information on the recent status of the field. Unresolved challenges facing the development of a malaria vaccine are also discussed
Design and in vivo pharmacodynamic evaluation of nanostructured lipid carriers for parenteral delivery of artemether: nanoject
No full textThe objective of the present investigation was to explore the potential of nanostructured lipid carriers (NLC) for the intravenous delivery of artemether (ARM), a poorly water-soluble antimalarial agent. The NLC of ARM (Nanoject) were formulated by employing a microemulsion template technique. The NLC were evaluated for particle size, encapsulation efficiency, in vitro drug release and in vitro hemolysis. The antimalarial activity of the Nanoject and conventional ARM injectable formulation was evaluated in Plasmodium berghei infected mice. The average particle size of Nanoject was 63±28 nm and the encapsulation efficiency was found to be 30±2%. The Nanoject released ARM in a sustained manner. In vitro haemolytic studies showed that Nanoject had lower haemolytic potential (~13%) as compared to all the components when studied individually. Nanoject showed significantly higher (P < 0.005) antimalarial activity as compared to the marketed injectable formulation. The antimalarial activity of Nanoject lasted for a longer duration (more than 20 days) indicating that Nanoject may be long-circulating in vivo. Nanoject showed significantly higher survival rate (60%) even after 31 days as compared to marketed formulation which showed 0% survival (100% mortality). This clearly indicates that Nanoject offers several advantages over the currently marketed oily intramuscular formulation (Larither®)
Self-Microemulsifiyng Suppository Formulation of β-Artemether
No full textParasitic diseases are of immense global significance as around 30% of world's population experiences parasitic infections. Among these, malaria is the most life-threatening disease. Various routes of administration have been explored for delivering antimalarial actives. The present investigation aims at formulating self-microemulsifying suppositories of β-artemether with faster onset of action and prolonged effect to be administered by rectal route. These were compared with conventional polyethylene glycol suppositories with respect to melting range, rheology, texture analysis, disintegration time, self microemulsification time, particle size, and drug content. In vitro drug release was studied by using USP apparatus II. Further, the suppositories were evaluated in murine model against virulent rodent malaria parasite Plasmodium berghei wherein the developed self-microemulsifying suppositories could sustain the activity (94%) for 20 days post infection. The survival of animals was also better as compared to the conventional formulation
Solid microemulsion preconcentrate (NanOsorb) of artemether for effective treatment of malaria
No full textA microemulsion preconcentrate was formulated on the basis of solubility of artemether (ARM) in the various oily phases and surfactants and phase diagrams. Various solid adsorbents were evaluated for their ability yield solid microemulsion preconcentrates (NanOsorb-ARM). NanOsorb-ARM on dilution yielded microemulsion with average globule size of 183 nm and polydispersity index of 0.498 when determined using photon correlation spectroscopy. The antimalarial activity of NanOsorb-ARM, ARM solution and marketed ARM formulation (Larither®) was evaluated in Plasmodium berghei infected mice as per Peter's four day protocol. The acute lethal dose and the subacute toxicity of NanOsorb-ARM were determined as per the method suggested in Organization for Economic Cooperation and Development (OECD) guidelines. The NanOsorb-ARM exhibited significantly higher antimalarial activity (P < 0.05) as compared to the marketed formulation of artemether (Larither®). Surprisingly, placebo NanOsorb also showed significantly higher antimalarial activity as compared to Larither® indicating that excipients used for the formulation of NanOsorb may have antimalarial activity. Subacute toxicity studies demonstrated that NanOsorb-ARM is comparatively safer than artemether oily solution with respect to survival, gross pathology, hematology and serum biochemistry in mice of both the genders
Enhanced antimalalarial activity of a prolonged release in situ gel of arteether–lumefantrine in a murine model
No full textDevelopment of SMEDDS using natural lipophile: application to β-Artemether delivery
No full textThe objective of the present investigation was to formulate self-microemulsifying drug delivery systems (SMEDDS) using a novel, indigenous natural lipophile (N-LCT) as an oily phase. SMEDDS based on N-LCT and commercially available modified oil (Capryol 90) were formulated and their application in improving the delivery of a lipophilic anti-malarial drug, β-Artemether (BAM) was also evaluated. BAM-loaded SMEDDS were characterized with respect to mean globule size and in vitro drug release profile in comparison to the marketed formulation (Larither®). Comparative in vivo anti-malarial performance of the developed SMEDDS was evaluated against the (Larither®) in Swiss male mice infected with lethal ANKA strain of Plasmodium berghei. The parameters studied were percent parasitemia, activity against time and animal survival period. Both the BAM-SMEDDS showed excellent self-microemulsification efficiency and released >98% of the drug in just 15 min whereas (Larither®) showed only 46% drug release at the end of 1 h. The mean globule size for optimized BAM-SMEDDS was <100 nm. The anti-malarial studies revealed that BAM-SMEDDS resulted in significant improvement in the anti-malarial activity (P < 0.05) as compared to that of (Larither®) and BAM solubilized in the oily phases and surfactant. The developed SMEDDS highlight safety for use and potential applications of indigenous natural lipophile in the development of novel colloidal drug carriers
