Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed. The studies reviewed herein highlight the clinical relevance of antiplatelet resistance, pharmacotherapy of antiplatelet agents predicting drug response, strategies for identifying aspirin resistance, pharmacogenetic variants of antiplatelet agents, miRNAs, and extracellular vesicles (EVs) as biomarkers toward the personalized approach in the management of acute ischemic stroke. The precise pathways contributing to antiplatelet resistance are not very well known but are presumably multi-factorial. It is essential to understand the clinical relevance of clopidogrel and aspirin-related single nucleotide polymorphism (SNPs) as potential predictive and prognostic biomarkers. Prasugrel is a next-generation antiplatelet agent that prevents ADP-platelet activation by binding irreversibly to P2Y12 receptor. There are sporadic reports of prasugrel resistance and polymorphisms in the Platelet endothelial aggregation receptor-1 (PEAR1) that may contribute to a change in the pharmacodynamics response. Ticagrelor, a direct-acting P2Y12-receptor antagonist, is easily absorbed and partly metabolized to major AR-C124910XX metabolite (ARC). Ticagrelor's primary active metabolite, ARC124910XX (ARC), is formed via the most abundant hepatic cytochrome P450 (CYP) enzyme, CYP3A4, and CYP3A5. The integration of specific biomarkers, genotype as well as phenotype-related data in antiplatelet therapy stratification in patients with acute ischemic stroke will be of great clinical significance and could be used as a guiding tool for more effective, personalized therapy.

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Metallic nanoparticles (MNPs) have been widely used for diagnostic and therapeutic purposes in clinical practice. A number of MNP formulations are being investigated in clinical trials for various applications. This increase in the use of NPs results in higher exposure to humans, leading to toxicity issues. Hence, it is necessary to determine the possible undesirable effects of the MNPs after in-vivo application and exposure. One of the main reasons for the toxicity of MNPs is the release of their respective metallic ions throughout the body. Many research studies are in progress investigating the various strategies to reduce the toxicity of MNPs. These research studies aim to change the size, dose, agglomeration, release, and excretion rates of MNPs. In this perspective review, we discussed the possible strategies to improve the therapeutic effects of MNPs through various processes, with lessons learned from the studies involving silver nanoparticles (AgNPs). We also discussed the ways to manage the toxicity of MNPs by purification, surface functionalization, synergistic effect, and targeted therapy approach. All these strategies could reduce the dose of the MNPs without compromising their therapeutic benefits, which could decrease the toxicity of MNPs. Additionally, we briefly discussed the market and toxicology testing for FDA-regulated MNPs.

Curcumin, a hydrophobic polyphenol isolated from dried rhizomes of turmeric exhibits diverse pharmacological activities including anti-bacterial.However, the clinical usefulness of curcumin was limited mainly due to low aqueous solubility and stability. The primary aim of the study was to prepare anionic surfactant based curcumin nanosuspension and to assess its in-vitro anti-bacterial efficacy on Escherichia coli in comparison with ethanolic solution of curcumin. Curcumin nanosuspension was prepared by nanoprecipitation method, characterized for the average particle size, span, uniformity, surface area, and surface morphology and assessed for its anti-bacterial activity against gram-negative bacteria Escherichia coli using agar well diffusion method. Prepared curcumin nanosuspension showed an average particle size of about 175 nm, span of about 1.5, uniformity of about 0.8, surface area of about 57 m 2 /g and nanoparticles were spherical in shape. Curcumin nanosuspension have shown significant (P<0.05) anti-bacterial activity against Escherichia coli at various concentrations in comparison with ethanolic solution of curcumin. We conclude that the size reduction of curcumin in nano range has increased the surface area resulting in increased aqueous solubility and reactability of curcumin, which in turn have increased the potency of curcumin nanosuspension.

In this study, analytical hierarchy process was used to select an optimal method for the preparation of dual loaded flavono polymeric nanoparticles. Analytical hierarchy process involves structuring multiple choice criteria into a hierarchy, assessing the relative importance of criteria, comparing alternatives for each criterion and determining an overall ranking of the alternatives. Hierarchy model was developed with the goal in the first level, 10 criteria in the second level and methods for the preparation of polymeric nanoparticles in the third level. To assess the relative importance of criteria, all criteria were compared with each other using Saaty’s scale. To compare the methods, all the methods for the preparation of polymeric nanoparticles were compared with each other for each criterion using Saaty’s scale, which leads to the formation of pair-wise comparison matrixes and consistency ratio was calculated for the each pair-wise comparison matrix. The study result showed that the consistency ratio of each pair-wise comparison matrix were well within acceptable limits. Of 10 criteria, reproducible results received the maximum overall priority weight followed by desirable size. Of 10 methods, nanoprecipitation method received the maximum overall priority weight followed by supercritical fluid technology. Analytical hierarchy process has identified reproducible results as criteria preference and nanoprecipitation as an optimal method for the preparation of dual loaded flavono polymeric nanoparticles. The study concludes that the analytical hierarchy process has played a vital role in selecting an optimal method for the preparation of dual loaded flavono polymeric nanoparticles.DOI: http://dx.doi.org/10.3329/icpj.v3i4.18264 International Current Pharmaceutical Journal, March 2014, 3(4): 247-253