Frontiers in drug delivery最新文献

Oral cancer, particularly oral squamous cell carcinoma (OSCC), poses significant challenges due to its aggressiveness, high metastatic potential, and resistance to conventional therapies. Recent advancements in drug delivery systems (DDS), including nanotechnology, intelligent hydrogels, lipid nanoparticles, and photodynamic therapy (PDT), offer innovative solutions for targeted treatment. These DDS utilize tumor-specific stimuli, such as pH variations, reactive oxygen species (ROS), and enzymatic activity, to achieve precise drug release while minimizing systemic toxicity. Cutting-edge technologies, such as microelectromechanical systems (MEMS) and artificial intelligence (AI), are enhancing the precision and personalization of DDS. Combination therapies integrating chemotherapy, PDT, and immunotherapy show promise in overcoming current limitations. Despite significant progress, challenges remain in scalability, patient-specific customization, and safety assessments. This review synthesizes the state-of-the-art in DDS for OSCC, highlighting future directions and the need for interdisciplinary collaboration to improve therapeutic outcomes and patient quality of life.

The progression of tumors and their response to treatment are significantly influenced by the presence of elevated mechanical solid stress. This solid stress compresses intratumoral blood vessels, leading to reduced blood flow (hypoperfusion) and insufficient oxygen levels (hypoxia), both of which hinder the delivery of oxygen and therapeutic agents. As a result, these conditions promote tumor growth, resistance to treatment, and ultimately undermine the effectiveness of therapies. To address these challenges, strategies like mechanotherapeutics and ultrasound sonopermeation have been developed to enhance blood flow and improve drug delivery to tumors. Mechanotherapy aims to reduce the mechanical stress and stiffness within tumors, helping to decompress vessels and restore normal perfusion. Ultrasound sonopermeation temporarily increases the permeability of blood vessel walls in a non-invasive manner, boosting blood flow and improving the delivery of therapeutic drugs. Here, we developed a mathematical model to explore the combined effects of mechanotherapeutics and sonopermeation on optimizing nano-immunotherapy efficacy. The model integrates complex interactions between key components involved in tumor progression, including tumor cells, immune cells, and vascular elements such as endothelial cells, angiopoietins, and vascular endothelial growth factor. To assess the model's validity, its predictions for key parameters, including tumor volume, functional vascular density, and hypoxia levels, were compared with experimental data, demonstrating a strong correlation, and confirming the accuracy of the mathematical framework. Furthermore, we carried out a parametric analysis to establish critical guidelines aimed at optimizing both the sequence and timing of experimental procedures. Specifically, we investigated the therapeutic outcomes of two treatment scenarios: applying sonopermeation first, followed by nano-immunotherapy, and vice versa. Also, we determined the optimal time interval between the application of sonopermeation and the commencement of the combined nano-immunotherapy regimen to maximize therapeutic efficacy.

Medical science stands on the brink of transformation thanks to nanotechnology's fast-paced development, which promises major advancements. Working with materials at the nanoscale within a 1-100 nm range allows scientists to tap into special physicochemical characteristics that open up new possibilities in diagnostics, drug delivery, and regenerative medicine. The review explores nanotechnology's revolutionary effects on healthcare by highlighting its roles in medical imaging applications and diagnostic procedures, drug delivery systems, tissue engineering, and vaccine development. The design principles of nanomaterials, which encompass synthesis methods alongside functionalization and characterization techniques, are presented here. This review analyzes the impact of artificial intelligence in nanomedicine alongside the enduring effects of nanomaterials and related ethical and safety issues. The review further combines multiple study findings to offer a thorough overview of nanotechnology's medical applications while suggesting research and clinical translation paths.

In recent years, there has been a significant increase in literature on emerging nanotechnologies, including nanoparticles, nanorobots, and exosomes, for various therapeutic applications. Additionally, politically driven research initiatives aimed at accelerating COVID-19 vaccine development have further amplified interest in nanoparticles as drug delivery systems. This article provides a personal perspective on the scientific claims surrounding nanoparticles by: (i) analyzing the historical evolution of their terminology, (ii) reviewing the most cited publications in the field, and (iii) offering a professional assessment to guide the next-generation of medicinal chemists. A key aspect of this discussion is the stealth effect, which refers to the ability of nanoparticles to evade recognition and clearance by the immune system, thereby prolonging their circulation time in the bloodstream. This property is essential for enhancing the efficacy of nanoparticle-based therapeutics by improving bioavailability and ensuring targeted drug delivery to diseased tissues. Furthermore, the continuing improvement in ligand-molecules and other functional tools have developed novel strategies and brand-new definition of delivery systems, such as Trojan Horse and Nanorobots.

Background: Many medicines for children taste bitter and unpleasant, presenting a significant barrier to effective pharmacotherapy. Anecdotally, this issue is widely recognized; however, empirical evidence on the consequences of unpalatable medicines remains scarce and fragmented. The objective of this scoping review was to investigate the impact of poor tasting pediatric medicines on patient acceptability, medication adherence, and/or treatment outcomes.

Methods: A literature search was performed in MEDLINE/PubMed, EMBASE and CINAHL from inception to June 2023. Eligibility criteria included interventional or observational studies conducted in children aged 0-18 years (population), administered an unpalatable oral medicine (exposure), with any reported impact on patient acceptability, medication adherence, and treatment effects (outcomes). Study screening and data extraction was completed using a standardized form on Covidence.

Results: After searching 2,282 citations and reviewing 429 full-text papers, 225 articles were included in the final analysis. The impact of poor-tasting medicines was observed across 77 diseases or indications, with 156 different unpalatable medicinal products identified. Outcomes were most frequently linked to reduced patient acceptability, with 64% of articles reporting rejection responses, the need for strategies to aid administration (from positive reinforcement to physical restraint and forced administration), and impacts on prescribing practices (e.g., use of non-first line alternative therapies). Medication adherence impacts were reported in 27% of the reviewed studies, where poor taste was reported as a barrier to adherence in chronic diseases and correlated with incomplete dose administration in acute conditions. A small number of studies linked palatability with treatment outcomes, including viral suppression in HIV and seizure control in epilepsy.

Conclusion: This review highlights the widespread adverse impact of poor-tasting pediatric medicines on patient experiences and outcomes, though the true extent of the issue may still be underreported. The problem affects children worldwide, across all age groups, and is frequently noted by parents, caregivers, and healthcare professionals in both clinical and domiciliary settings. These findings emphasize the need for the development and prescription of more palatable medicines for children, as well as the advancement of more universal taste-masking strategies to address this widespread problem.

Introduction: Improving the palatability of bitter-tasting medication for pediatric populations has long presented a challenge. Taste blockers are being researched as a potential solution; however, end-user perspectives and needs related to this concept have not been explored. The objectives of this research were 1) to understand current experiences of administering bitter-tasting medication; 2) the evaluation of a consumer-targeted product profile (CTPP) for a taste blocker including attributes such as form and duration of action; and 3) whether there is a need to support improved acceptability and adherence with a taste blocker taken before the bitter-tasting medication.

Methods: Our study consisted of simultaneous qualitative and quantitative phases, involving caregivers and healthcare providers with experience administering medications to children aged 2-17 years. Qualitative research was conducted with 120 caregivers and 92 healthcare providers using a range of methods. Focus groups (FGs) were conducted in Kenya, Nigeria and Zimbabwe (grouped as Sub-Saharan Africa (SSA) but not intended to be representative of the region as a whole) with caregivers of children who had taken medication for HIV, TB, pneumonia, or malaria (including for seasonal prevention) within the past 6 months. Telephone in-depth interviews (TDIs) were conducted with caregivers of children with chronic illnesses in the United States. Face-to-face in-depth interviews (IDIs) and TDIs were conducted with healthcare providers. The quantitative part of the study was conducted with n = 1,815 caregivers and n = 859 healthcare providers using face-to-face computer-assisted interviews (CAPI) in SSA, and via online panel research in the United States A CTPP was used as the stimulus for discussion. Participants were asked about their experiences in giving bitter-tasting medication to their children or patients, their perceptions of and willingness to try a taste blocker, and their preferences for specific product attributes.

Results: Participants described how bitter-tasting medications create challenges in multiple areas: for caregivers, children, their daily life and routines, healthcare providers, and children's perceptions of healthcare. In SSA, 28.9% of caregivers reported that their children always or regularly refused medication due to bitter taste, while 57.9% reported this in the United States. Another 36.2% and 29.1% respectively experienced this sometimes or occasionally. Over 80% of providers in all countries stated that bitter taste impacts adherence to both long and short-term medication. The preferred attributes of the taste blocker were a sweetened and flavored lollipop form with a maximum total duration of up to approximately 1h, and with a total taste block achieved as soon as possible. Overall, responses to the concept of the taste blocker were positive from caregiv

[This corrects the article DOI: 10.3389/fddev.2024.1382266.].

Introduction: Well-organized nasal-associated lymphoid tissue (NALT) has been identified in the pharyngeal and tubal tonsils of both adults and children, and diffuse NALT has been identified in the superior, middle and inferior turbinate regions of children. However, it is not clear how to target these NALT sites with aerosolized vaccines. We explored whether head position and/or angle and distance of device insertion could be used to target fluorescein aerosol to NALT sites in three-dimensional printed models of the intranasal airways of an 18- and a 5-year-old (yo).

Methods: Three head positions (upright [Up], tilted back 45° [45] and supine [Su]), two angles of insertion (30° and 45°) and two distances of insertion (6 mm and 9 mm) were tested. Fluorescein aerosol was generated by an Aptar Pharma BiVax 200 µL intranasal atomizer. Percent fluorescein deposition was quantified in the anterior nose, the upper horizontal third of the model (superior turbinate region), middle third (middle turbinate), lower third (inferior turbinate and nasopharynx combined) and exit filter.

Results: Mean percent deposition in both models was <0.5% in the upper third and on the exit filter for all test conditions. A multivariate analysis showed that deposition in either model was unaffected by the angles of insertion and distances of insertion. However, middle third deposition was significantly higher in the 5-yo than in the 18-yo (p = 0.01) and anterior nose deposition was higher in the 18-yo than in the 5-yo (p < 0.01). When data from both models were combined, middle third deposition was highest in the supine position with Up < 45 < Su (p < 0.01) and lower third deposition was highest in the upright position with Up > 45 > Su (p = 0.03).

Discussion: These results suggest that, in individuals with similar nasal airway dimensions as our models: 1) supine and upright head positions might be used to target delivery of aerosolized vaccines generated by the BiVax intranasal atomizer to NALT sites in the middle turbinate and the inferior turbinate and nasopharynx combined, respectively; 2) delivery to the middle turbinate may be higher in children ≤5-yo; and 3) deposition in the anterior nose may be higher in adults, for all head positions. In vivo tests are needed to confirm these findings.