ABSTRACT
HYPOTHESIS: One of the main assets of crosslinked polymer-shelled microbubbles (MBs) as ultrasound-active theranostic agents is the robustness of the shells, combined with the chemical versatility in modifying the surface with ligands and/or drugs. Despite the long shelf-life, subtle modifications occur in the MB shells involving shifts in acoustic, mechanical and structural properties. EXPERIMENTS: We carried out a long-term morphological and acoustic evolution analysis on elastomeric polyvinyl-alcohol (PVA)-shelled MBs, a novel platform accomplishing good acoustic and surface performances in one agent. Confocal laser scanning microscopy, acoustic spectroscopy and AFM nanomechanics were integrated to understand the mechanism of PVA MBs ageing. The changes in the MB acoustic properties were framed in terms of shell thickness and viscoelasticity using a linearised oscillation theory, and compared to MB morphology and to nanomechanical analysis. FINDINGS: We enlightened a novel, intriguing ageing time evolution of the PVA MBs with double behaviour with respect to a crossover time of â¼50â¯days. Before, significant changes occur in MB stiffness and shell thickness, mainly due to a massive release of entangled PVA chains. Then, the MB resonance frequency increases together with shell thickening and softening. Our benchmark study is of general interest for emerging viscoelastomeric bubbles towards personalised medicine.
ABSTRACT
BACKGROUND: Patient adherence to therapeutic regimens is extremely important to successful treatment of acute otitis media. Among pediatric patients medication palatability, particularly that of oral suspensions, is essential for patient acceptance, therapeutic compliance and successful outcome. METHODS: A series of six randomized, single blind, crossover trials were conducted, each comparing cefdinir oral suspension with one of the following antibiotic oral suspensions: amoxicillin/clavulanate potassium; cefprozil; or azithromycin. Each medication comparison was evaluated in a single center and multicenter study. Subjects 4 to 8 years of age were asked to taste and smell each medication and assign preference using a visual "smile-face" scale. Ratings were converted to a numeric score ranging from 5 ("really good") to 1 ("really bad"). RESULTS: Among the 715 subjects 85% rated the taste of cefdinir as good or really good, the highest possible ratings; 63% of subjects assigned the same ratings to amoxicillin/clavulanate potassium, cefprozil or azithromycin. Seventy-one percent rated the smell of cefdinir as good or really good; 64% assigned the same ratings to the comparators. CONCLUSIONS: Based on the findings from these trials, children 4 to 8 years of age preferred the taste and smell of cefdinir oral suspension to that of the comparator agents.
