Intracellularly targeted delivery system based on PLGA nanoparticles decorated with endoplasmic reticulum (ER)-targeting or control peptides and encapsulating antigenic peptide and fluorescent marker, was developed and characterized. The cellular uptake by dendritic cells (murine DC2.4 cells), intracellular trafficking, and cross-presentation efficiency of this delivery system were studied in vitro. The prepared nanoparticles (an average diameter of ~350 nm) efficiently encapsulated antigenic peptide and fluorescent marker and gradually released them over several days. Yet, the nanoparticles' size was small enough to allow their efficient endocytosis by the antigen-presenting cells in vitro. Surface conjugation of the targeting or control peptides enhanced the endocytosis of the nanoparticles, affected their intracellular trafficking, and induced prolonged low-magnitude cross-presentation of the antigenic peptide. We demonstrated in vitro that the intracellular fate of nanoparticulate drug delivery systems can be altered by their surface decoration with peptidic targeting residues. More detailed investigation is required to determine the mechanisms and therapeutic potential of intracellular targeting of nanodelivery systems in vivo for the goal of an anticancer vaccine.

Medical treatment takes place primarily in the ambulatory setting. Most individuals who experience symptoms go to their family physicians, whereas only a minority of patients turn to secondary or tertiary medical care. 1 The number of patient visits for patients 65 years of age and older increased by about 13%Letters to the Editor e727

Global Initiative for Asthma 2019 guidelines recommend to avoid strengthening patients’ reliance on relievers since they increase exacerbation risk. Our aim was to examine the association between reliever inhalers overuse and all-cause healthcare utilization (HCU). A retrospective study among Clalit Health Services (CHS) adult enrollees (n = 977) for 2012–2017. Reliever inhalers overuse was defined as consistent prescription refills of ≥ 3 canisters annually. Adherence to controllers was calculated using the proportion of days covered. HCU included: hospitalizations, diagnostic and surgical procedures, medications, emergency room (ER) visits, and clinic visits. 27% of the study population (n = 264) consistently refilled ≥ 3 relievers prescriptions annually, and had higher adherence to controllers (0.38 vs. 0.24, p < 0.001). Their total 6-year HCU costs were not higher than that of others ($5,550 vs. $5,562, p = 0.107). Most HCU components [including hospitalization (p = 0.405) and ER visits (p = 0.884)] were comparable; however, medication costs were higher ($1734 vs. $1504, p < 0.001). A multivariable ordered-logit model revealed that frequent and regular use of relievers was not associated with higher HCU costs (OR = 0.82, 95% CI 0.62–1.09, p = 0.175). Higher adherence to maintenance and reliever therapy (OR = 2.18, 95% CI 1.44–3.28, p < 0.001), other controllers (OR = 3.30, 95% CI 2.11–5.16, p < 0.001), and nebulized SABAs and SAMAs (OR = 1.08, 95% CI 1.02–1.14, p = 0.007) was associated with higher costs. Overuse of reliever inhalers was prevalent and associated with higher adherence to controllers, yet not associated with higher all-cause HCU. This highlights the need to examine the sources of elevated usage in order to develop intervention strategies to optimize pharmaceutical therapy of asthma patients.