Introduction: Nanomedicine has emerged as a major field of academic research with direct impact on human health. While a first generation of products has been successfully commercialized and has significantly contributed to enhance patient’s life, recent advances in material design and the emergence of new therapeutics are contributing to the development of more sophisticated systems. As the field matures, it is important to comprehend the challenges related to nanoparticle commercial development for a more efficient and predictable path to the clinic.
Areas covered: The review provides an overview of nanoparticle-based delivery systems currently on the market and in clinical trials, and discuss the principal challenges for their commercial development, both from a manufacturing and regulatory perspective, to help gain understanding of the translational path for these systems.
Expert opinion: Clinical translation of nanoparticle-based delivery systems remains challenging on account of their 3D nanostructure and requires robust nano-manufacturing process along with adequate analytical tools and methodologies. By identifying early enough in the development the product critical attributes and understanding their impact on the therapeutic performance, the developers of nanopharmaceuticals will be better equipped to develop efficient product pipelines. Second-generation products are expected to broaden nanopharmaceutical global market in the upcoming years. 相似文献
Interleukin (IL)-12p40, a subunit of IL-12p70 and IL-23, has previously been shown to inhibit IL-12p70 activity and interferon-gamma (IFN-gamma) production. However, recent evidence has suggested that the role of IL-12p40 is more complex. To study the contribution of IL-12p40 to immune responses against mycobacterial infections, we have used transgenic (tg) mice overexpressing IL-12p40 under the control of a major histocompatibility complex-II promoter. The IL-12p40 transgene was expressed during steady state at concentrations of 129 +/- 25 ng/ml of serum and 75 +/- 13 ng per spleen, while endogenous IL-12p40 was hardly detectable in control littermates. Bacille Calmette-Guérin (BCG) infection strongly induced the expression of IL-12p40 transgene in infected organs, and IL-12p40 monomeric and dimeric forms were identified in spleen of IL-12p40 tg mice. Excessive production of IL-12p40 resulted in a 14-fold increase in IL-12p70 serum levels in tg mice versus non-transgenic mice. IL-23 was also strongly elevated in the serum and spleens of IL-12p40 tg mice through BCG infection. While IFN-gamma and tumour necrosis factor protein levels were similar in IL-12p40 tg and non-transgenic mice, Th2 type immune responses were reduced in IL-12p40 tg mice. The number of BCG granulomas and macrophage expressing inducible nitric oxide synthase were similar in IL-12p40 tg and non-transgenic mice. IL-12p40 tg mice were as resistant as non-transgenic mice to BCG and Mycobacterium tuberculosis infections as they could efficiently control bacillary growth. These data show that high amounts of IL-12p40 promotes IL-12p70 and IL-23 formation, but that does not affect T helper 1 type immune responses and granuloma function, thus leading to normal mycobacterial clearance in infected organs. 相似文献
Although peaks and troughs in cognitive performance characterize our daily functioning, time-of-day fluctuations remain marginally considered in the domain of cognitive psychology and neuropsychology. Here, we attempt to summarize studies looking at the effects of sleep pressure, circadian variations, and chronotype on cognitive functioning in healthy subjects. The picture that emerges from this assessment is that beyond physiological variables, time-of-day modulations affect performance on a wide range of cognitive tasks measuring attentional capacities, executive functioning, and memory. These performance fluctuations are also contingent upon the chronotype, which reflects interindividual differences in circadian preference, and particularly upon the synchronicity between the individuals' peak periods of circadian arousal and the time of the day at which testing occurs. In themselves, these conclusions should direct both the clinician's and the researcher's attention towards the utmost importance to account for time-of-day parameters when assessing cognitive performance in patients and healthy volunteers. 相似文献
Bone infections are difficult to treat and can lead to severe tissue destruction. Acute bone infections are usually caused by Staphylococcus aureus. Osteoclasts, which belong to the monocyte/macrophage lineage, are the key cells in bone infections. They are not well equipped for killing bacteria and may serve as a reservoir for bacterial pathogens. Silver has been known for centuries for its bactericidal activity. Here, we investigated the bactericidal effects of nano-silver particles in bacteria infected human osteoclasts. We found that nano-silver in per se non-toxic concentration enhanced the bactericidal activity in osteoclasts against intracellular Methicillin-resistant, virulent Staphylococcus aureus. The reduced bacterial survival in nano-silver pretreated cells correlated with increased reactive oxygen responses towards the invading pathogens. Overall, these results indicate that nano-silver compounds should be considered as an effective treatment and prevention option for bacterial bone and orthopedic implant infections. 相似文献
The incidence of glioblastoma (GBM) has increased in patients aged 70 years or older, and will continue to grow. Elderly GBM patients have been excluded from most clinical trials; furthermore, optimal care management as well as benefit/risk ratio of GBM treatments are still being debated. This study describes oncological patterns of care, prognostic factors, and survival for patients ≥70 years in France. We identified patients over 70 with newly diagnosed and histologically confirmed GBM on data previously published by the French Brain Tumor DataBase. We included 265 patients. Neurological deficits and mental status disorders were the most frequent symptoms. The surgery consisted of resection (RSn?=?95) or biopsy (Bn?=?170); 98 patients did not have subsequent oncological treatment. After surgery, first-line treatment consisted of radiotherapy (RTn?=?76), chemotherapy (CTn?=?52), and concomitant radiochemotherapy (CRCn?=?39). The median age at diagnosis was 76, 74, and 73 years, respectively, for the untreated, B?+?RT and/or CT, RS?±?RT and/or CT groups. Median survival (in days, 95 % CI) with these main strategies, when analyzed according to surgical groups, was: B-CTn?=?41, 199[155–280]; B-CRCn?=?21, 318[166–480]; B-RTn?=?37, 149[130–214]; RS-CTn?=?11, 245[211–na]; RS-CRCn?=?18, 372[349–593]; RS-RTn?=?39, 269[218–343]. This population study for elderly GBM patients is one of the most important in Europe, and could be considered as a historical cohort to compare future treatments. Moreover, we can hypothesize that elderly patients (versus patients <70 years) are undertreated. Karnofsky performance status seems to be the most relevant clinical predictive factor, and RS and CRC have a positive impact on survival for elderly GBM patients in the general population, at least when feasible. 相似文献