Delivery Methods Research Articles

Nasal Vaccine: A Special Prominence on SARS-CoV-2

Abstract: Nasal administration of mucosal medications and vaccines is an alternate and promising method of drug and vaccine delivery. Mucosal pathways can be used selectively for various disorders due to many benefits. Many initiatives are now being made to yield effective medications and cutting-edge nasal delivery systems. The structure of the nasal cavity and key features were discussed in this review. With a focus on vaccine distribution, the benefits, successes, and difficulties of using the nasal route for medical purposes were examined. The strong result supports the benefits and security, of the safety of nasal medication and vaccination administration. This alternate path may help many unmet medical needs and may also make big vaccination drives or expensive, protracted chronic therapies possible. Today, despite some lingering criticism, the area of nasal medicine and vaccine delivery is expanding quickly, supported by recent advancements in nanotechnology, imaging, and administration devices. The variety of drugs that have been licensed for nasal delivery is expected to increase significantly.

Educational Gaming and Situational Interest for Higher Education Students

InPraktijk is an educational game developed for first year physical therapy students. The game aims to use playful learning to optimize students' interest in interacting with course content. This project is a first step in achieving a versatile educational game platform optimized for engaging, playful learning that can be applied across multiple educational programmes. The project seeks to improve students’ motivation to engage with course materials outside of class time and explore the relationship between playful learning and situational interest. Our research is focused on a deeper understanding of the relationship between situational interest and playful learning. The InPraktijk game, developed in collaboration with Game Tailors, will be used as a tool to test this relationship. Through the game, we will collect quantitative data on time played, drop out location and situational interest using the situational interest scale. This work in progress paper covers the design for study 1 of the InPraktijk project. The study indicates whether the gamified interaction with course content can generate more situational interest compared to traditional content delivery methods. The results will provide insights into the effectiveness of the InPraktijk app in stimulating situational interest. Our findings will guide the direction of follow-up studies on further game optimization and the integration of playful games in educational structures.

Nutrition support in children with medical complexity and chronic critical illness: A narrative review.

Children with medical complexity (CMC) and children with chronic critical illness (CCI) represent growing populations with high healthcare use and dependence on specialized care, both in the hospital and community setting. Nutrition assessment and delivery represent critical components of addressing the short-term and long-term health needs for these populations across the care continuum. This article provides a framework and reviews existing literature for the assessment of nutrition status and subsequent delivery of nutrition prescriptions in CMC and children with CCI. The specific aims are to (1) describe the epidemiology of health services experience for CMC and children with CCI, with a focus on their nutrition outcomes; (2) detail how to assess their nutrition status and energy requirements; (3) review methods of delivery of the nutrient prescription; (4) introduce perioperative considerations; (5) highlight examples of special populations of CMC and children with CCI; and (6) propose future research initiatives to improve nutrition and overall outcomes for these populations.

Evaluation of integrated sustainable last-mile delivery methods in an intuitionistic fuzzy environment

Evaluation of integrated sustainable last-mile delivery methods in an intuitionistic fuzzy environment

Rhythm in the Poetic Introduction

Rhythm is a poetic necessity for constructing a poem, which in turn gives us other rhythms and other phonemes in the background of the meter, and behind the words, and hence the meter does not constitute a major value in constructing a poem unless it is linked to other artistic elements of writing poetry. In this section, we address the rhythmic phenomenon in the introductions to poetry collections in various forms of Arabic poetry: classical, free metrical, and prose poetry, by reading a number of diverse poetic models, starting from the fact that poetry is not poetry, and that poetic meters do not form a poem except to the extent that the poet invests in other elements of poetry, in the image, style, density and depth of language, and rhetorical diversification in performing the poem, and also departing from the pattern by renewing and developing and striving to create advanced innovations in the broad rhythmic horizon, and in the formative and linguistic horizon of poetic introductions, and in this section we have monitored a group of rhythmic phenomena such as: repetition, phonemes of language, the rhythm of the visual space of writing, and the relationship between effect and reception. In light of this awareness, poetic introductions may come in a multi-rhythmic form that does not necessarily stop at the inherited poetic form, but rather varies in its performance and in the methods of delivery, investing the space of the poetic page in conveying the poet’s semantic vision.

Cell Therapy for Retinal Degenerative Diseases: Progress and Prospects.

Background/Objectives: Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are leading causes of vision loss, with AMD affecting older populations and RP being a rarer, genetically inherited condition. Both diseases result in progressive retinal degeneration, for which current treatments remain inadequate in advanced stages. This review aims to provide an overview of the retina's anatomy and physiology, elucidate the pathophysiology of AMD and RP, and evaluate emerging cell-based therapies for these conditions. Methods: A comprehensive review of the literature was conducted, focusing on cell therapy approaches, including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs), and retinal progenitor cells. Preclinical and clinical studies were analyzed to assess therapeutic potential, with attention to mechanisms such as cell replacement, neuroprotection, and paracrine effects. Relevant challenges, including ethical concerns and clinical translation, were also explored. Results: Cell-based therapies demonstrate potential for restoring retinal function and slowing disease progression through mechanisms like neuroprotection and cell replacement. Preclinical trials show promising outcomes, but clinical studies face significant hurdles, including challenges in cell delivery and long-term efficacy. Combination therapies integrating gene editing and biomaterials offer potential future advancements. Conclusions: While cell-based therapies for AMD and RP have made significant progress, substantial barriers to clinical application remain. Further research is essential to overcome these obstacles, improve delivery methods, and ensure the safe and effective translation of these therapies into clinical practice.

PELATIHAN PEMBUATAN MEDIA PEMBELAJARAN BERBASIS IT DI DESA LUNU KECAMATAN NUNLEU KABUPATEN TIMOR TENGAH SELATAN

The learning presented by teachers must be interesting, so that it can arouse students' enthusiasm and interest in learning, therefore teachers need to be equipped to create creative learning activities, including by utilizing IT which is centered on the use of Canva and learning videos via Power Point. Training through PkM activities aims to provide teachers with an understanding of the importance of IT-based learning media, as an effort to improve the process and quality of learning in schools, and how schools cannot avoid facing the era of modernization and the internet. PkM (Community Service) activities are carried out in the form of education and training in making IT-based learning media. The training material delivery method consists of lecture, question and answer, discussion and direct practice in creating IT-based learning media. The training results show that participants' understanding and mastery of the material regarding creating IT-based learning media has increased after attending the training compared to before. Apart from that, training participants already have the skills and ability to create their own learning media, such as making learning videos using Power Point and using the Canva application to create weekly and monthly activity schedules to support the smooth running of various activities at school.

Transdermal Drug Delivery Systems (TDDS): Recent Advances and Failure Modes.

Transdermal drug delivery systems (TDDS), commonly refered to as "patches", present a nonintrusive technique to provide medication without the need for invasive procedures. These products adhere to the skin and gradually release a specific dosage of medicine at a defined rate into the bloodstream. Compared with other methods of drug delivery, TDDS offer benefits such as reduced invasiveness, convenience for patients, and avoidance of the metabolic processes that occur when drugs are orally consumed. Throughout time, TDDS have been used to provide medications for various medical conditions (such as nicotine, fentanyl, nitroglycerin, and clonidine), and their potential for delivering biologics is currently being explored. This review investigates the current literature on the drug delivery efficacy of medical TDDS through the transdermal route. Additionally, the review addresses potential risks and failure modes associated with TDDS design and development as well as strategies for mitigating such risks. A thorough understanding of failure modes provides a blueprint to mitigate failure and produce high-quality efficacious therapeutics.

Ocular Drug Delivery Routes: Diseases Overview and Advanced Administration Methods

The eye is anatomically divided into two: the anterior segment and the posterior segment. The anterior segment comprises structures located at the front of the eye, including the cornea, iris, ciliary body, pupil, aqueous humor, and lens. In contrast, the posterior segment encompasses structures located at the back of the eye, such as the vitreous, retina, choroid, macula, and optic nerves. Numerous diseases arise due to anomalies occurring within these ocular tissues. When formulating drugs for ocular conditions, it is crucial to consider the specific segment of the eye affected by the disease. Various routes of drug administration and dosage forms are available for delivering medications to the eye. These include topical forms such as solutions, emulsions, suspensions, ointments, and gels. Additionally, drugs can be administered through routes such as intravitreal, suprachoroidal, intracorneal, or subconjunctival. Furthermore, novel methods of drug delivery to the eye have emerged, including inserts, films, contact lenses, and microneedles. The aim of this review is to discuss innovative drug delivery systems and explain in detail the different routes of drug administration to the eye with examples from the current literature.

A Meta-Analysis of the Association Between the Hold Me Tight Program and Couples’ Relationship Adjustment

In this meta-analysis, the authors tested the overall effect of Hold Me Tight (HMT), a relationship education program for couples based in emotionally focused therapy, on couples’ relationship adjustment. Using a detailed search process, we identified and analyzed eight quantitative, single-group comparison studies. Studies included predominantly cisgender, straight couples (N = 310) in dyadic, monogamous relationships from the United States, Canada, and the Netherlands. The eight studies also included evaluations of online and in-person delivery methods, as well as eight-week groups and one- and two-day workshops. Across the studies, we found that participation in HMT was associated with a small, statistically significant effect (d = 0.377) on couples’ self-reported relationship adjustment, lending support that HMT may be an effective program for couples. Few available studies limited our ability to test additional outcomes or explore moderators of the effect, which are key areas for future research.

Angiotensin 1 peptide-conjugated CdSe/ZnS quantum dots for cardiac-specific hydrogen sulfide targeted therapy in myocardial ischemia-reperfusion injury.

Myocardial ischemia/reperfusion (I/R) injury remains a major obstacle in cardiovascular therapies. Hydrogen sulfide (H2S) shows promise for mitigating I/R injury, but conventional delivery methods, such as NaHS injections or adenovirus-mediated CSE gene therapy, face low efficiency and systemic side effects. This study explores the use of angiotensin 1 (AT1) peptide-conjugated CdSe/ZnS quantum dots (QDs) for targeted delivery of cystathionine-γ-lyase (CSE) plasmids to the myocardium, aiming to boost local H2S production and minimize I/R injury. CdSe/ZnS QDs were conjugated with AT1 peptides to create a nanocarrier system capable of delivering the CSE plasmid specifically to the myocardium. In vivo fluorescence imaging confirmed heart-specific accumulation. Myocardial infarct size, cardiac function, cell death, and oxidative stress were evaluated. Endoplasmic reticulum stress and mitophagy markers, including CHOP/GRP78/eIF2α, were analyzed, and the CHOP gene's role was further assessed using an adenovirus vector. The AT1-conjugated nanocarriers significantly increased CSE expression in the myocardium, as confirmed by fluorescence imaging, without affecting other organs. This localized delivery reduced myocardial infarct size, improved cardiac function, and decreased oxidative stress and cell death. Importantly, a reduction in endoplasmic reticulum stress and mitophagy markers was observed, suggesting that cardioprotection was mediated via the CHOP/GRP78/eIF2α signaling pathway. Reintroduction of CHOP using an adenovirus vector reversed these protective effects, confirming the pathway's involvement. This study demonstrates that AT1 peptide-conjugated QDs can effectively deliver CSE plasmids to the heart, providing significant protection against I/R injury through enhanced localized H2S production. This approach offers a promising, targeted, and side-effect-free therapy for myocardial I/R injury, with potential for clinical translation.

Recent Advances in Ocular Drug Delivery: Insights into Lyotropic Liquid Crystals.

Background/Objectives: This review examines the evolution of lyotropic liquid crystals (LLCs) in ocular drug delivery, focusing on their ability to address the challenges associated with traditional ophthalmic formulations. This study aims to underscore the enhanced bioavailability, prolonged retention, and controlled release properties of LLCs that significantly improve therapeutic outcomes. Methods: This review synthesizes data from various studies on both bulk-forming LLCs and liquid crystal nanoparticles (LCNPs). It also considers advanced analytical techniques, including the use of machine learning and AI-driven predictive modeling, to forecast the phase behavior and molecular structuring of LLC systems. Emerging technologies in biosensing and real-time diagnostics are discussed to illustrate the broader applicability of LLCs in ocular health. Results: LLCs are identified as pivotal in promoting targeted drug delivery across different regions of the eye, with specific emphasis on the tailored optimization of LCNPs. This review highlights principal categories of LLCs used in ocular applications, each facilitating unique interactions with physiological systems to enhance drug efficacy and safety. Additionally, novel applications in biosensing demonstrate LLCs' capacity to improve diagnostic processes. Conclusions: Lyotropic liquid crystals offer transformative potential in ocular drug delivery by overcoming significant limitations of conventional delivery methods. The integration of predictive technologies and biosensing applications further enriches the utility of LLCs, indicating a promising future for their use in clinical settings. This review points to continued advancements and encourages further research in LLC technology to maximize its therapeutic benefits.

Clinical applications of STING agonists in cancer immunotherapy: current progress and future prospects.

The STING (Stimulator of Interferon Genes) pathway is pivotal in activating innate immunity, making it a promising target for cancer immunotherapy. STING agonists have shown potential in enhancing immune responses, particularly in tumors resistant to traditional therapies. This scholarly review examines the diverse categories of STING agonists, encompassing CDN analogues, non-CDN chemotypes, CDN-infused exosomes, engineered bacterial vectors, and hybrid structures of small molecules-nucleic acids. We highlight their mechanisms, clinical trial progress, and therapeutic outcomes. While these agents offer significant promise, challenges such as toxicity, tumor heterogeneity, and delivery methods remain obstacles to their broader clinical use. Ongoing research and innovation are essential to overcoming these hurdles. STING agonists could play a transformative role in cancer treatment, particularly for patients with hard-to-treat malignancies, by harnessing the body's immune system to target and eliminate cancer cells.

Fetal-hope study: Home monitoring of fetal heart rate in SSA + pregnant women: Rationale and design

IntroductionWorldwide, approximately 0.5–1 % of women of childbearing age are positive for anti-Ro/SSA antibodies and anti-La/SSB. The presence of these antibodies may be responsible for the appearance of Neonatal Lupus. The pathogenesis of this disease is probably mediated by the binding of these antibodies to fetal myocardiocytes. The typical manifestation is atrioventricular block (AVB), which in most cases is complete (CHB). AVB commonly develops between 16 and 26 weeks of gestation and is cause of severe heart failure. CHB appears to be irreversible, but anecdotal reports suggest that treatment of second-degree AVB can restore sinus rhythm. ObjectiveThe aim of the study is to evaluate the reliability of home monitoraing of fetal heart rate by the use of a hand-held device, extablishing the incidence of fetal AVB in pregnant women positive for anti-Ro/SSA autoantibodies and to evaluate whether early treatment can influence the course of the disease. MethodsAnti-Ro/SAA positive pregnant women are currently recruited from 11 Italian centers in a prospective observational study. Patients are instructed to use a portable doppler between 16 and 34 weeks of gestation and to monitor the fetal heart rate (FHR) every 8 h. In case of FHR anomalies patients will contact the reference center which will guarantee an echocardiogram within 8 h and in case of anomalies, adequate treatment. All patients will undergo check-ups at 20, 26 and 32 weeks of gestation, with the collection of information on the course of the maternal disease, on the use of drugs and on instrumental monitoring progress.After birth, data will be collected on the outcome of pregnancy and the methods of delivery. Newborns will also be evaluated for the possible appearance of clinical signs of Neonatal Lupus. ResultsFetal-Hope is actually enrolling Patients from involved Centers. ConclusionsFetal-Hope is the first European study assessing the reliability of home monitoring of fetal heart rate using a handheld device, determining the incidence of fetal atrioventricular block (AVB) in pregnant women positive for anti-Ro/SSA autoantibodies and assessing whether early intervention can alter the disease’s progression.

One-Pot Synthesis of Chiral Cysteine-Capped Gold Nanoparticles for Use as Vaccine Adjuvants in Mice

The influence of chirality on the biological activity of nanoparticles, including their interaction with the immune system, is a growing area of interest. This study presents a one-pot synthesis method for 15 nm L-cysteine or D-cysteine capped gold nanoparticles (L/D-Cys-GNPs) and evaluates their immunological potential as adjuvants in mice. The synthesized GNPs were comprehensively characterized using UV-visible absorption spectroscopy, FTIR, CD spectra, and TEM, revealing enhanced stability and effective internalization by human umbilical vein endothelial cells (HUVEC), with L-Cys-GNPs exhibiting a higher uptake rate. In vivo immunization studies demonstrated that L-Cys-GNPs significantly boosted the production of anti-ovalbumin(OVA) IgG antibodies compared to D-Cys-GNPs (>66 folds), underscoring the importance of chiral surface properties in modulating immune responses. However, the encapsulation of GNPs in liposomes negated the chiral effect, suggesting that delivery methods may influence the interaction of GNPs with the immune system. The findings highlight the role of chirality in vaccine development and provide insights into targeted antigen delivery systems. This work contributes to the understanding of chirality in vaccine development and paves the way for the design of more effective vaccines against challenging diseases.

The characteristics of a fibroid in pregnancy can influence the perinatal outcome.

To determine whether fibroids affect perinatal outcomes and whether women who undergo fibroid surgery before pregnancy have better perinatal outcomes than those who have fibroids during pregnancy. The study also analyzes the optimal time interval between myomectomy and pregnancy and the characteristics of fibroids during pregnancy that affect perinatal outcomes. In both groups, fibroids' size, number, and location were analyzed to determine their influence on perinatal outcomes. The perinatal outcome is determined by gestational age, birth weight, Apgar score, intrauterine growth retardation, placental complications, and delivery method. A study was conducted on the perinatal outcomes of 338 women who had uterine fibroids during pregnancy and those who had undergone fibroid surgery before pregnancy. The medical records of women who gave birth at a tertiary university hospital were analyzed in this retrospective study. Women with submucosal fibroids have a lower gestational age of delivery (P = 0.0371), and those who operated on a higher number of fibroids before pregnancy had newborns with lower birth weights (P < 0.0001). Submucosal fibroids during pregnancy increase the chances of cesarean delivery (P = 0.0354). 14% of newborns have an Apgar score of less than seven within the first minute of birth in fibroids larger than 7cm (P < 0.0001). There is a statistically significant difference in the perinatal outcome of newborns depending on the number, size and placement of uterine fibroids in both observed groups.

In focus: Engaging Black and African American women in oncology supportive care interventions.

54 Background: For individuals navigating cancer, unaddressed psychosocial needs can adversely impact quality of life, treatment adherence, and healthcare expenditures. It is recognized that African American cancer survivors are more likely to experience distress, yet they are underrepresented in studies that evaluate interventions. Mind Over Matter (MOM) is a five-week psychoeducational program aimed at bolstering emotional coping skills. A previous study among predominantly White female-identifying breast cancer survivors revealed improvements from pre to post-MOM for anxiety, depression, and physical symptom severity and interference; no data exists for women who identify as Black and/or African American. This presentation will illustrate the strategies and processes implemented to recruit, consent, and retain Black and African American cancer survivors to test the feasibility and acceptability of MOM. Methods: In forming the research team, the diversity in institutions, experience, racial and cultural identities, and professional perspectives were prioritized. As a result of this process, team members were social workers and psychologists, one was at an HBCU institution, and another was a patient advocate from the Black community who was hired and trained enabling full participation in the research process. To improve access all aspects of the study were available online and the intervention was offered virtually in the evening to support participants' availability. Efforts were made to build relationships with non-profit organizations, then disseminating the study through emails, healthcare systems, and social media. Results: During the 3-month recruitment period, 79 individuals expressed interest in the study via email and the study website. Of these, 40 participants (50.6%) enrolled in the study, surpassing the goal of 27. Half of the enrolled survivors learned about the study through community, medical, and academic organizations, while 20% and 10% were referred via the home health system and social media, respectively. 17.5% were referred from unspecified sources. Conclusions: Through robust team development, strategic community partnerships, using a study design that addressed common barriers (e.g., program hours and delivery method, tech orientation, incentives) and a high touch approach, this study successfully enrolled half of the Black and African American female-identified cancer survivors who expressed interest in this mixed-methods study. Clinical trial information: NCT06168825 .

"Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability".

The oral route stands out as the most commonly used method for drug administration, prized for its non-invasive nature, patient compliance, and easy administration. Several elements influence the absorption of oral medications, including their solubility, permeability across mucosal membranes, and stability within the gastrointestinal (GI) environment. Research has delved into comprehending physicochemical, biochemical, metabolic, and biological obstacles that impact the bioavailability of a drug. To improve oral drug absorption, several pharmaceutical technologies and delivery methods have been studied, including cyclodextrins, micelles, nanocarriers, and lipid-based carriers. This review examines both traditional and innovative drug delivery methods, as well as the physiological and pharmacological barriers influencing medication bioavailability when taken orally. Additionally, it describes the challenges and advancements in developing formulations suitable for oral use.

Uptake of Mesenchymal Stem Cell-Derived Exosomes in Mouse Brain through Intranasal Delivery.

Exosomes are nanoscale extracellular vesicles that widely participate in intercellular communication. An increasing number of studies have reported on the neuroprotective effects of stem cell-derived exosomes in brain diseases through various delivery methods. However, only a few reports are available on the delivery and uptake of stem cell-derived exosomes in the brains of mice of different ages. PKH-26-labelled mesenchymal stem cell-derived exosomes were collected, and their uptake was investigated in the brains of mice aged 2 weeks, 2 months, and >6 months, 24 hours after intranasal delivery. No exosomes were distributed in the whole brains of 2-week-old mice after 24 hours of intranasal delivery. However, a small number of exosomes were found in the olfactory bulb, cortex, and hippocampus of 2-month-old mice, with no exosomes observed in the cerebellum. In contrast, a large number of exosomes were ingested in all brain regions, including the olfactory bulb, cortex, hippocampus, and cerebellum, of >6-month-old mice. Exosomes can enter the brains of adult mice through intranasal administration, but there are differences in the uptake rate among mice of different ages. These findings provide a theoretical basis for the future clinical administration of exosomes for treating brain disorders.

The Regional Climate Center Program—Past, Present, and Future: Reflections from 40 Years of Regional Climate Services

Abstract Since its inception in 1983, NOAA’s Regional Climate Center (RCC) Program has been providing timely, customized climate services for decision making across all climate-sensitive sectors. Through this 40-yr period, the RCC Program has not only seen but also has played an active role in, the evolution of climate services from the days of climate data libraries—where books of data were consulted to fulfill simple data requests—to coproduced tools that can calculate sectoral-specific, on-the-fly climate analyses in a matter of seconds. With new technologies emerging, the RCC Program is poised to build on its reputation as a trusted climate service provider by incorporating advanced methods for climate service delivery to continue to meet the needs of the nation. This publication will provide a look back at the evolution of regional climate services over the past 40 years, along with a vision for the future.