Infectious diseases are a major driver of morbidity and mortality globally. Treatment of malaria, tuberculosis and human immunodeficiency virus infection are particularly challenging, as indicated by the ongoing transmission and high mortality associated with these diseases. The formulation of new and existing drugs in nano-sized carriers promises to overcome several challenges associated with the treatment of these diseases, including low on-target bioavailability, sub-therapeutic drug accumulation in microbial sanctuaries and reservoirs, and low patient adherence due to drug-related toxicities and extended therapeutic regimens. Further, nanocarriers can be used for formulating vaccines, which represent a major weapon in our fight against infectious diseases. Here we review the current burden of infectious diseases with a focus on major drivers of morbidity and mortality. We then highlight how nanotechnology could aid in improving existing treatment modalities. We summarize our progress so far and outline potential future directions to maximize the impact of nanotechnology on the global population.
Multigram drug depot systems for extended drug release could transform our capacity to effectively treat patients across a myriad of diseases. For example, tuberculosis (TB) requires multimonth courses of daily multigram doses for treatment. To address the challenge of prolonged dosing for regimens requiring multigram drug dosing, we developed a gastric resident system delivered through the nasogastric route that was capable of safely encapsulating and releasing grams of antibiotics over a period of weeks. Initial preclinical safety and drug release were demonstrated in a swine model with a panel of TB antibiotics. We anticipate multiple applications in the field of infectious diseases, as well as for other indications where multigram depots could impart meaningful benefits to patients, helping maximize adherence to their medication. A gastric resident drug delivery system for prolonged gram-level dosing of tuberculosis treatment.
The serum concentration-time curve of valproic acid was followed in 25 children after single oral doses of the drug and at steady-state. Total body clearance (CL), half-life (t 1/2), and apparent volume of distribution (Vd) were calculated from the terminal portion of the curve and from the area under the serum concentration-time curve (AUC). The CL and Vd were significantly greater at steady-state (0.42 +/- 0.20 ml/min/kg and 0.231 +/- 0.067 L/kg, respectively) than after a single dose (0.32 +/- 0.13 ml/min/kg and 0.191 +/- 0.055 L/kg, respectively). This difference was most pronounced in patients with valproic acid dosage increases in excess of 20% and no change in their concurrent anticonvulsant therapy between the single-dose and steady-state study periods. The t 1/2 was not significantly different between the 2 study periods. There was a significant correlation between age and both CL and Vd after single doses and at steady-state. The t 1/2 did not appear to be age related. These results suggest that the adequacy of the dosage regimen must be determined during maintenance therapy rather than extrapolated from data obtained after a single dose. Re-evaluation of therapy as the child grows older may also be necessary in view of the age-related differences in valproic acid pharmacokinetics which this study has demonstrated.
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