Primaquine and chloroquine nano-sized solid dispersion-loaded dissolving microarray patches for the improved treatment of malaria caused by Plasmodium vivax

Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

Adequate characterization of NPs (nanoparticles) is of paramount importance to develop well defined nanoformulations of therapeutic relevance. Determination of particle size and surface charge of NPs are indispensable for proper characterization of NPs. DLS (dynamic light scattering) and ZP (zeta potential) measurements have gained popularity as simple, easy and reproducible tools to ascertain particle size and surface charge. Unfortunately, on practical grounds plenty of challenges exist regarding these two techniques including inadequate understanding of the operating principles and dealing with critical issues like sample preparation and interpretation of the data. As both DLS and ZP have emerged from the realms of physical colloid chemistry - it is difficult for researchers engaged in nanomedicine research to master these two techniques. Additionally, there is little literature available in drug delivery research which offers a simple, concise account on these techniques. This review tries to address this issue while providing the fundamental principles of these techniques, summarizing the core mathematical principles and offering practical guidelines on tackling commonly encountered problems while running DLS and ZP measurements. Finally, the review tries to analyze the relevance of these two techniques from translatory perspective.

Summary Background Plasmodium vivax exacts a significant toll on health worldwide, yet few efforts to date have quantified the extent and temporal trends of its global distribution. Given the challenges associated with the proper diagnosis and treatment of P vivax, national malaria programmes—particularly those pursuing malaria elimination strategies—require up to date assessments of P vivax endemicity and disease impact. This study presents the first global maps of P vivax clinical burden from 2000 to 2017. Methods In this spatial and temporal modelling study, we adjusted routine malariometric surveillance data for known biases and used socioeconomic indicators to generate time series of the clinical burden of P vivax. These data informed Bayesian geospatial models, which produced fine-scale predictions of P vivax clinical incidence and infection prevalence over time. Within sub-Saharan Africa, where routine surveillance for P vivax is not standard practice, we combined predicted surfaces of Plasmodium falciparum with country-specific ratios of P vivax to P falciparum. These results were combined with surveillance-based outputs outside of Africa to generate global maps. Findings We present the first high-resolution maps of P vivax burden. These results are combined with those for P falciparum (published separately) to form the malaria estimates for the Global Burden of Disease 2017 study. The burden of P vivax malaria decreased by 41·6%, from 24·5 million cases (95% uncertainty interval 22·5–27·0) in 2000 to 14·3 million cases (13·7–15·0) in 2017. The Americas had a reduction of 56·8% (47·6–67·0) in total cases since 2000, while South-East Asia recorded declines of 50·5% (50·3–50·6) and the Western Pacific regions recorded declines of 51·3% (48·0–55·4). Europe achieved zero P vivax cases during the study period. Nonetheless, rates of decline have stalled in the past five years for many countries, with particular increases noted in regions affected by political and economic instability. Interpretation Our study highlights important spatial and temporal patterns in the clinical burden and prevalence of P vivax. Amid substantial progress worldwide, plateauing gains and areas of increased burden signal the potential for challenges that are greater than expected on the road to malaria elimination. These results support global monitoring systems and can inform the optimisation of diagnosis and treatment where P vivax has most impact. Funding Bill & Melinda Gates Foundation and the Wellcome Trust.