Delivery System Research Articles

Late Life Homelessness: A Definition to Spark Action and Change.

Comprehensive definitions of social issues and populations can set the stage for the development of responsive policies and practices. Yet despite the rise of late- life homelessness, the phenomenon remains narrowly understood and ill-defined. This paper and the definition that ensued is based on the reconceptualization of interview data derived from a critical ethnography conducted in Montreal, Canada with older homeless persons (N=40) and service providers (N=20). Our analysis suggests that definitions of late life homelessness must include four intersecting components: 1) age, eligibility, and access to services ; 2) disadvantage over the life course and across time; 3) social and spatial processes of exclusion that necessitate aging in 'undesirable' places; and 4) unmet needs that result from policy inaction and non-response. The new definition derived from these structural and relational components captures how the service gaps and complex needs identified in earlier works are shaped by delivery systems and practices whose effect is compounded over time. It provides an empirically grounded and conceptually solid foundation for the development of better responses to address homelessness in late life.

Novel paradigm of therapeutic intervention for skin cancer: challenges and opportunities

Abstract Background Skin cancer continues to be an imperative global health issue, urging continuous exploration of treatment methodologies. Conventional treatments for skin cancer include surgical interventions, immunotherapy, targeted therapy, chemotherapy, and radiation therapy. However, these methods often present obstacles like treatment resistance, systemic toxicity, limited effectiveness in advanced stages, infection risk, pain, long recovery, and impact on healthy tissue. Main body of the abstract Nanomedicine holds promise by facilitating precise drug administration, early detection, and heightened therapeutic efficiency via targeted and localized delivery systems. The integration of nanomedicine into skin cancer alleviation therapies demonstrates optimistic outcomes, including refined drug delivery, augmented bioavailability, minimized adverse effects, and potential theranostic applications. Recent breakthroughs in nanomedicine have propelled advancements in skin cancer treatment, showing significant potential in transforming the treatment paradigm. The presents review provides comprehensive aspects of existing skin cancer treatments and their challenges, spotlighting recent breakthroughs propelled by nanomedicine. Short conclusion This abstract delineates the present landscape of skin cancer treatments, underscores their constraints, and highlights recent strides in nanomedicine that have the potential to transform the paradigm of skin cancer treatment, ultimately elevating patient prognosis. Importantly, the present review emphasizes substantial challenges that hinder the clinical translation of nanomedicines and suggests possible remedies to surpass them. Graphic abstract

Investigation of Folate-Functionalized Magnetic-Gold Nanoparticles Based Targeted Drug Delivery for Liver: In Vitro, In Vivo and Docking Studies.

Magnetic nanoparticles used for targeted drug administration present a promising approach in cancer treatment owing to its notable advantages, such as targeted and enhanced encapsulation ability and improved bio protection compared with conventional drug delivery methods. Au shell-iron core nanoparticles (Fe3O4@Au) were manufactured by a chemical process, coated with dextran to encapsulate curcumin, and functionalized for precision drug delivery using folic acid to combat liver cancer. Dynamic light scattering, scanning electron microscopy, transmission electron microscopy, vibrational spectroscopy, and magnetometry were applied to assess the synthesis of the Fe3O4@Au-DEX-CU-FA compound. The mean size, zeta potential, and polydispersity of Fe3O4@Au-DEX-CU-FA were 63.3 ± 2.33 nm, -68.3 ± 1.78 mV, and 0.041 ± 0.008, respectively. Molecular docking models were created to examine the relationship between Fe3O4@Au-CU and BCL-XL, BAK, and to identify potential binding sites. The loading efficiency and release profile tests examined the medication delivery system's ability. MTT assay was subsequently utilized to determine the optimal dosage and therapeutic efficacy of Fe3O4@Au-DEX-CU-FA on cancer SNU-449 and healthy THLE-2 cell lines. Flow cytometry demonstrated that Fe3O4@Au-DEX-CU-FA effectively induced cancer cell death. Fe3O4@Au-DEX-FA showed a regulated release profile of free curcumin at 37 °C and pH values of 7.4 and 5.4. Real-time PCR revealed increased BAK expression and decreased BCL-XL expression. Nude tumor-bearing mice were used for in vivo experiments. Fe3O4@Au-DEX-CU-FA treatment dramatically reduced the swelling size compared with free CU and control treatments. It also resulted in a longer lifespan, expanded splenocyte proliferation, increased IFN-γ levels, and decreased IL-4 levels. The regular cells showed no cytotoxic effect compared with the cancer type, confirming that Fe3O4@Au-DEX-CU-FA maintained its potent anticancer actions. The data suggests that Fe3O4@Au-DEX-CU-FA possesses a promising potential as a therapeutic agent for combating tumors.

Exploring the Potential of Ellagic Acid in Gastrointestinal Cancer Prevention: Recent Advances and Future Directions.

Gastrointestinal (GI) cancers are a significant global health concern with diverse etiologies and limited treatment options. Ellagic acid (EA), a natural polyphenolic compound, exhibits promising anticancer properties against various GI malignancies. In this article, we have reviewed recent research on the anticancer potential of EA across esophageal, gastric, colorectal, pancreatic, and liver cancers. In esophageal cancer, EA inhibits the formation of O6-methylguanine (O6-meGua) adducts induced by carcinogens like N-nitrosomethylbenzylamine (NMBA), thereby suppressing tumor growth. Additionally, EA inhibits STAT3 signaling and stabilizes tumor suppressor proteins, showing potential as an anti-esophageal cancer agent. In gastric cancer, EA regulates multiple pathways involved in cell proliferation, invasion, and apoptosis, including the p53 and PI3K-Akt signaling pathways. It also demonstrates anti-inflammatory and antioxidant effects, making it a promising therapeutic candidate against gastric cancer. In colorectal cancer (CRC), EA inhibits cell proliferation, induces apoptosis, and modulates the Wnt/β-catenin and PI3K/Akt pathways, suggesting its efficacy in preventing CRC progression. Furthermore, EA has shown promise in pancreatic cancer by inhibiting nuclear factor-kappa B, inducing apoptosis, and suppressing epithelial-mesenchymal transition. In liver cancer, EA exhibits radio-sensitizing effects, inhibits inflammatory pathways, and modulates the tumor microenvironment, offering potential therapeutic benefits against hepatocellular carcinoma. Studies on EA potential in combination therapies and the development of targeted delivery systems are required for enhanced efficacy against gastrointestinal cancers.

Intranasal Delivery of Lipid Nanoparticles: A Ground-breaking Approach for Brain Targeting

Abstract: In the present scenario, various novel delivery systems are available for drug delivery to systemic circulation. So, to accomplish a greater therapeutic effect, the nature of the drug delivery is very important. This delivery is one of the innovative approaches where the drug is targeted to the brain through the nasal cavity. As we know, the human brain is the most crucial part of the body that controls various functions of our system. So, safely reaching the targeted site of the brain is necessary to achieve brain specificity. This delivery system helps us to tackle the problems that may arise in the other delivery system and helps the drug reach the brain without any difficulties. The major obstacles we faced during this delivery were the blood-brain barrier (BBB) and the brain-cerebrospinal fluid barrier. So, if we target the drug to the brain, then we have to overcome these challenges, and before that, we must have a clear understanding of the targeted site and the mechanism behind the drug targeting. Advancements in science and technology have helped discover many recent strategies and formulations available for intranasal delivery. The development of lipid nanoparticles is one of the primitive approaches for targeting any type of drug(hydrophilic/lipophilic) in the brain. So, the aim of this review mainly focused on the mechanism of intranasal delivery, the devices used, and some recent strategies like the development of lipid nanoparticles, surface-modified lipid nanocarriers, and noseto-brain patches. This review article also includes a few FDA-approved formulations for nose-to-brain delivery and their regulatory aspects related to clinical trials and future perspectives.

Prospective Approaches of Herbal Novel Delivery System with Special Reference to the Herbal Nanosciences

: Medicinal and culinary uses of plants date back centuries. Projects on a global scale are conducting laboratory research to identify plants with therapeutic properties, with the ultimate goal of developing such compounds into medicines with acceptable drug delivery mechanisms and bringing them to market. Non-synthetic medications derived from plant or herbal sources have attracted a lot of interest because of their high tolerability and low likelihood of adverse medication reactions. All diseases, the theory goes, can be cured by something found in nature. Medicines can be taken in a wide variety of forms, including tablets, capsules, powders, semi-liquid extracts, tinctures, decoctions, medicinal teas, solutions, and more. Longer release, patient adherence, and other objectives necessitate adjustments to herbal medications. Researchers into novel drug delivery systems had hitherto overlooked herbal remedies due to a lack of scientific validation and the challenges inherent in processing, standardizing, extracting, and identifying them. Transdisciplinary research and cuttingedge isolation, purification, and identification techniques have led to the development of novel herbal compositions. Bioactive plant extracts and phytoconstituents are used in a wide variety of Nano- Emulsions, microspheres, transferosomes, implants, and ethosomes. Compared to herbal remedies, novel formulations fared better. Among these advantages are increased solubility, bioavailability, toxicity, pharmacological activity, stability, delivery duration, and resistance to physical and chemical degradation. As a result, the pharmacokinetic and pharmacodynamic properties of herbal medications can be enhanced by the use of novel drug delivery systems, making them safer and more effective. : This article aims to provide a concise description of the many new drug delivery techniques that have been created for the administration of herbal medications. The ultimate goal is to increase the efficacy of therapies and to learn more about their significance and worldwide appeal.

Mapping the Nanotechnology Patent Landscape in the Field of Cancer.

Currently, cancer is still a significant disease that seriously endangers human health. Therefore, advanced diagnostic technology and treatment protocols are urgently needed. The rapid development of nanotechnology is expected to provide new ideas for cancer diagnosis and treatment. The research aims to comprehensively demonstrate the hotspots of nanotechnology applications in cancer. In this study, an International Patent Classification codes co-occurrence network is constructed to visualize the technology landscape by simultaneously locating and ranking technologies that play an integral role in nanotechnology diffusion and bridging in the field of cancer. In addition, community identification and topic modeling highlight the latent topics in patent documents. The visualization results of the patent network yield five main clusters: Cluster 0 is a nanoparticle composition delivery system with liposomes as the primary carrier. Cluster 1 is mainly represented by nano-immunotherapy with immune checkpoint inhibitors. Cluster 2 is nano phototherapy based on photodynamic therapy and photothermal therapy. Cluster 3 is diagnostic imaging involving nanotechnology. Cluster 4 is a drug delivery system with nanovesicles and albumin nanoparticles as carriers. It was found that carriers represented by liposomes, vesicles, and albumin nanoparticles are essential nanomaterials in the current anticancer drug delivery systems. Integrating next-generation immunosuppressants and nanotechnology will become an important development direction for future immunotherapy. Organic/inorganic nanomaterials are pivotal in cancer imaging diagnosis and phototherapy.

Recent advancements in novel formulations of anti-psoriatic agents for effective delivery: clinical importance and patent survey.

Objectives An autoimmune-mediated dermatological ailment featuring recurrent episodes is acknowledged as psoriasis. Around the world, 2-3% of people suffer from this autoimmune skin condition. The primary goal of the current review is to analyse and determine the effectiveness of conventional and emerging nano technological strategies to alleviate psoriasis and discuss future perspectives. Evidence acquisition A thorough search of numerous electronic databases, including Science Direct, Scopus, Google Scholar, Clinical Trials, Google Patents, Research Gate, and PubMed, yielded all the data used in this review paper about the management of psoriasis via various anti-psoriatic agent and nanotechnology approaches. Keywords such as topical, liposomes, niosomes, micro needles, clinical trials, patents, pathogenesis, biosimilars, cytokines, and other pertinent words were investigated. Results Nano technological approaches are gaining prominence since they enable targeted delivery, rapid onset of action with limited systemic exposure. Researchers have investigated innovative, alternative therapeutic approaches that are both secure and efficient for treating psoriatic conditions. Further, the potential role of numerous psoriatic conventional therapies has been explored. The patents granted or in process to address psoriasis via topical route have been well explored. Modern nanotechnology has made it possible for pharmaceuticals to be delivered with improved physical, chemical, pharmacokinetic, and pharmacodynamic qualities. Despite extensive research complete cure for psoriasis is hampered. Conclusion Relying on the extensive literature review, it can be inferred that nanoparticles based novel delivery strategies have the possibility of enhancing the pharmacological activity and eliminating or resolving problems associated with this ailment. The different drug delivery systems available for the treatment of psoriasis along with the clinical trials in different stages, patents in process and granted, the commercialized status of therapeutic molecules, and the future of research in this area have been thoroughly reviewed.

Engineering CaP-Pickering emulsion for enhanced mRNA cancer vaccines via dual DC and NK activations

mRNA delivery systems, such as lipid nanoparticle (LNP), have made remarkable strides in improving mRNA expression, whereas immune system activation operates on a threshold. Maintaining a delicate balance between antigen expression and dendritic cell (DC) activation is vital for effective immune recognition. Here, a water-in-oil-in-water (w/o/w) Pickering emulsion stabilized with calcium phosphate nanoparticles (CaP-PME) is developed for mRNA delivery in cancer vaccination. CaP-PME efficiently transports mRNA into the cytoplasm, induces pro-inflammatory responses and activates DCs by disrupting intracellular calcium/potassium ions balance. Unlike LNP, CaP-PME demonstrates a preference for DCs, enhancing their activation and migration to lymph nodes. It elicits interferon-γ-mediated CD8+ T cell responses and promotes NK cell proliferation and activation, leading to evident NK cells infiltration and ameliorated tumor microenvironment. The prepared w/o/w Pickering emulsion demonstrates superior anti-tumor effects in E.G7 and B16-OVA tumor models, offering promising prospects as an enhanced mRNA delivery vehicle for cancer vaccinations.

Effect of sub-acute exposure of metal-organic framework-199 on cognitive function and oxidative stress level of brain tissue in rat

Metal-Organic Framework-199 (MOF-199) is a subgroup of MOFs that is utilized in different medical fields including biocompatibility and drug delivery. In the current study, the effect of sub-acute exposure to MOF-199 on spatial memory, working memory, inflammatory mediators’ expression, and oxidative stress level of brain tissue has been investigated. Thirty-two male Wistar rats were randomly divided into four groups as vehicle, MOF-199 at doses 0.3, 3, or 6 mg/kg. After four injections of relevant interventions via tail vein during 14 days, behavioral parameters were investigated using Y-maze and Morris Water Maze (MWM) tests. Oxidative stress was measured by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) tests. The expression levels of TNF-α and IL-1β were assessed by quantitative real-time reverse-transcription PCR (qRT-PCR). No significant differences were observed in working memory, spatial learning and memory of MOF-199 receiving rats. Additionally, the level of oxidative stress and inflammatory genes expression were not remarkably changed in the brain tissues of MOF-199 treated rats. Despite the lack of remarkable toxic effects of sub-acute exposure to MOF-199, more studies with a longer duration of administration are necessary to use this substance for drug delivery systems in diseases related to the nervous system.

In‐Silico Nanomedical Exploration of Mefloquine Drug Transport Using Pegylated Graphene Oxide Nanocarrier

AbstractThis study investigates the in‐silico transport of mefloquine (MQ) by using graphene oxide (GO) and polyethylene glycol (PEG)‐functionalized GO nanocarriers. Density functional theory (DFT) calculations are performed to explore the molecular interactions, electronic properties, thermodynamics, and release kinetics of MQ‐GO and MQ‐GO/PEG complexes across different phases and environmental conditions. Results indicate a strong affinity between MQ and both types of nanocarriers, with the adsorption energies ranging from −59.14 to −143.16 kcal mol−1, particularly in acidic environments. This suggests a potential for targeted drug delivery in acidic tumor micro‐environments. The incorporation of PEG, enhances stability and compatibility across phases, with chi interaction parameters of between 1.36 and 28.47, and the energy of mixture values, ranging from 0.80 to 16.86 kcal mol−1. The release time of MQ from the nanocarriers, varies significantly, depending on the adsorption energy, and ranges from 2.03 × 1030 to 6.98 × 1091 milliseconds across different phases, highlighting the need for further optimization of the drug delivery systems. The findings of this study provide valuable insights into the design and development of novel nanomedicines, based on MQ and GO nanocarriers, with implications for malaria treatments.

Formulation, Design, Optimization, and Characterization of Novel Long-acting Injectable Dosage Form of Anti-psychotic Drug

Background: The current research aimed to create and analyze a new long-acting Brexpiprazole (BRX) injectable for successful anti-psychotic drug therapy in order to decrease dosage frequency and increase patient compliance. Systems for drug transport to particular body sites or regulating release rates with accuracy are known as drug delivery systems (DDS). By affixing the drug to a carrier particle like liposomes, nanoparticles, microspheres, etc., which modifies the drug's absorption and release properties, using carrier technology, drugs may be delivered in an intelligent manner. Methods: Utilizing Resomer RG 502 H and RESOMER® RG 752 H extended-release Polymer, Using a quasi-emulsion solvent diffusion, microspheres were made, and emulsification and solvent evaporation process. Results: The produced microspheres were assessed for stability tests, in vitro drug release, flow characteristics, and drug entrapment efficiency. FTIR experiments were used to establish how well the drug excipients worked together. The acarbose microspheres that were created had an 89.9 to 96.1 percent drug entrapment efficiency. The impact of factors like polymer content on medication release was studied. The Stability study of the formulation was carried out under different conditions, and data were established. Comparative pharmacokinetic studies between marketed oral formulation and Brexpirazole microsphere test formulations in Wistar/SD Rats were carried out and concluded. Conclusion: Brexpiprazole (BRX) novel long-acting injectable formulation, could be used effectively for the treatment of mentally challenged anti-psychotic patients worldwide.

Development of a nanomachine for efficient drug delivery to the brain

Recently, bottom-up technologies, in particular the utilization of self-assembly of functional polymers to form nanostructures in solutions have been collecting attention. These technologies are being explored for various applications, especially for usage in therapeutics. One of the goals of such studies is to develop a drug delivery system (DDS) that delivers bioactive substances to specific targets within our body, eliciting the desired functionality. The authors have been developing "nanomachines" using biocompatible polymers to safely and efficiently deliver drugs mainly to tumors. The aim of this study is to utilize our expertise in designing a nanomachine to develop a cutting-edge nanomachine that can efficiently penetrate the blood-brain barrier (BBB) and deliver drugs to the brain parenchyma. Furthermore, leveraging this "nanomachine" technology, the authors are advancing the "Hayabusa Nanomachine," which can non-invasively collect and detect brain molecules, correlating them with various biological processes, ultimately leading to a better understanding of brain function and diseases. This paper also introduces the concept and ongoing efforts to the development of "Hayabusa Nanomachines," which have the potential to revolutionize existing approaches in this field.

Starch-based "smart" nanomicelles: Potential delivery systems for doxorubicin.

Vesicular nanosystems are a cornerstone to the contemporary drug delivery paradigm owing to their ability to encapsulate a variety of drug molecules, which improves the overall pharmacokinetics and bioavailability of the cargo drug. These systems have proven potential in the delivery of hydrophobic chemotherapeutic "Doxorubicin" (DOX), which faces frequent challenge relating to its nonspecific interactions, dose-limiting toxicity (myelosuppression being the most common manifestation), and short half-life (distribution half-life of 5 min, terminal half-life of 20-48 h), which limit its overall clinical effectiveness. "Smart" nanomicelles with stimuli-responsive linkages take advantage of tumor microenvironment for deploying the cargo drug at the target site, which prevents nonspecific distribution and, hence, low toxicity. Similarly, those with stealth properties evade protein response, which triggers the immunogenic response. The nanomicelles co-loaded with magnetic nanoparticles provide additional utility such as contrast enhancement agents in theranostics. Overall, the starch-based nanomicelles prove to be an excellent delivery system for overcoming the limitations associated with the conventional DOX delivery regime.

Development of Enteric Diclofenac Sodium Microparticles Through a Spray-Drying Process Facilitated by Different Aqueous Dispersion Systems

The objective of this study was to prepare enteric diclofenac sodium microparticles using an aqueous dispersion system via spray-drying. Two aqueous-based solvent systems, phosphate buffer at pH 7.0 and ammonium hydrogen carbonate solution, were employed as the feed dispersion media in the spray-drying process based on the solubility characteristics of Eudragit® L100. At a drug-to-polymer ratio of 1:1, the optimal solids concentration in the feed dispersion was determined to be 2% w/v, as it enabled an approximately 5-30 µm smooth-surfaced spherical microparticle with a high production yield. Diclofenac sodium was efficiently encapsulated within the microparticles, existing as solid dispersion in a partially amorphous form. Notably, the spray-drying conditions utilized in this study obviated the need for further heating for microparticles prepared using ammonium hydrogen carbonate solution, as the residual ammonium could be completely eliminated during the spray-drying process. The two-stage biorelevant drug release profile of enteric microparticles demonstrated their ability to inhibit drug dissolution under acidic conditions while facilitating drug release under basic conditions. The phosphate buffer-based microparticles exhibited greater protection efficiency under acidic conditions compared to ammonium hydrogen carbonate-based systems, despite residual alkaline salt being present in the microparticles. These results validate the potential of the developed microparticles for use as an enteric drug delivery system.

Chasing New Cancer Treatments: Current Status and Future Development of Boron Neutron Capture Therapy

Boron neutron capture therapy (BNCT) is expected to be a promising next-generation cancer treatment. In 2020, Japan, which has led the research on this treatment modality, was the first country in the world to approve BNCT. The boron agents that have been clinically applied in BNCT include a caged boron compound (mercaptoundecahydrododecaborate: BSH) and a boron-containing amino acid (p-boronophenylalanine: BPA). In particular, the BPA preparation Steboronine® is the only approved drug for BNCT. However, the problem with BPA is that it is poorly retained in the tumor and has very low solubility in water. This cannot be overlooked for BNCT, which requires large amounts of boron in the tumor. The high dosage volume, together with low tumor retention, leads to reduced therapeutic efficacy and increased physical burden on the patient. In the case of BSH, its insufficient penetration into the tumor is problematic. Based on drug delivery system (DDS) technology, we have developed a next-generation boron pharmaceutical superior to Steboronine®. Our approach involves the redevelopment of BPA using innovative ionic liquid formulation technology. Here, we describe previous boron agents and introduce our recent efforts in the development of boron compounds.

Unlocking the Potential of Drug Delivery Systems: A Comprehensive Review of Formulation Strategies and Technologies in the Field of Pharmaceutics

: The creation of innovative drug delivery systems to enhance therapeutic effectiveness, safety, and patient compliance has resulted in considerable developments in pharmaceutics in recent years. The most recent formulation techniques and technologies are reviewed in this article to improve medication distribution and accomplish specific therapeutic goals. : This article thoroughly summarizes the most recent formulation techniques and technologies used to enhance medication delivery and provide specific therapeutic effects. It discusses the variety of medication delivery methods, including nanoparticles, liposomes, micelles, and dendrimers, and explores the application of nanotechnology and biotechnology in drug delivery. Additionally, the paper emphasizes the significance of targeted drug delivery systems and their capacity to cross biological barriers including the blood-brain barrier and tumor microenvironment. : The review also addresses the challenges faced in developing and commercializing drug delivery systems and suggests potential solutions to overcome them. Furthermore, the article emphasizes the role of computational modeling and simulation in designing and optimizing drug delivery systems. : Overall, this review paper offers insightful information for pharmaceutics researchers, scientists, and practitioners that will help in the creation of novel drug delivery systems that improve patient outcomes and quality of life.

Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial

Ataxia telangiectasia is a multisystem disorder with progressive neurodegeneration. Corticosteroids can improve neurological functioning in patients with the disorder but adrenal suppression and symptom recurrence on treatment discontinuation has limited their use, prompting the development of novel steroid delivery systems. The aim of the ATTeST study was to evaluate the efficacy and safety of intra-erythrocyte delivery of dexamethasone sodium phosphate compared with placebo in children with ataxia telangiectasia. This multicentre, randomised, double-blind, placebo-controlled, phase 3 trial was done at 22 centres in 12 countries (Australia, Belgium, Germany, India, Israel, Italy, Norway, Poland, Spain, Tunisia, the UK, and the USA). Eligible participants were children aged 6 years or older weighing more than 15 kg who met clinical criteria for ataxia telangiectasia but who had preserved autonomous gait. Participants were randomly assigned (1:1:1) to low-dose (approximately 5-10 mg), or high-dose (approximately 14-22 mg) intra-erythrocyte dexamethasone sodium phosphate, or placebo, using an independent interactive web response system, with minimisation for sex and age (6-9 years vs ≥10 years). Intravenous intra-erythrocyte dexamethasone sodium phosphate was administered once a month for 6 months. Participants, employees of the sponsor, investigators, all raters of efficacy endpoints, and central reviewers were masked to treatment assignment and dose allocations. The primary efficacy endpoint was change in the modified International Cooperative Ataxia Rating Scale (mICARS) from baseline to month 6, assessed in the modified intention-to-treat (mITT) population, which included all randomly assigned participants who received at least one dose of study drug and had at least one post-baseline efficacy assessment. This trial is registered with Clinicaltrials.gov (NCT02770807) and is complete. Between March 2, 2017, and May 13, 2021, 239 children were assessed for eligibility, of whom 176 were randomly assigned. One patient assigned to high-dose intra-erythrocyte dexamethasone sodium phosphate did not initiate treatment. 175 patients received at least one dose of treatment (59 patients received the low dose and 57 received the high dose of intra-erythrocyte dexamethasone sodium phosphate, and 59 received placebo). The mITT population comprised 164 participants (56 children in the low-dose group, 54 children in the high-dose group, and 54 in the placebo group). Compared with the placebo group, no differences were identified with regard to change in mICARS score from baseline to 6 months in the low-dose group (least squares mean difference -1·37 [95% CI -2·932 to 0·190]) or the high-dose group (-1·40 [-2·957 to 0·152]; p=0·0765). Adverse events were reported in 43 (73%) of 59 participants in the low-dose group, 47 (82%) of 57 participants in the high-dose group, and 43 (73%) of 59 participants in the placebo group. Serious adverse events were observed in six (10%) of 59 participants in the low-dose group, seven (12%) of 57 participants in the high-dose group, and seven (12%) of 59 participants in the placebo group. There were no reports of hyperglycaemia, hypertension, hirsutism, or Cushingoid appearance in any of the treatment groups, nor any treatment-related deaths. Although there were no safety concerns, the primary efficacy endpoint was not met, possibly related to delays in treatment reducing the number of participants who received treatment as outlined in the protocol, and potentially different treatment effects according to age. Studies of intra-erythrocyte delivery of dexamethasone sodium phosphate will continue in participants aged 6-9 years, on the basis of findings from subgroup analyses from this trial. EryDel and Quince Therapeutics.

Synthesis and Characterization of Baicalein-loaded Aquasomes: An In vitro and In silico Perspective for Diabetes Mellitus.

Millions of individuals worldwide suffer from metabolic abnormalities induced by diabetes. Baicalein, a flavonoid, has shown several properties in various treatments with potential properties, including anti-inflammatory, antioxidant, and anti-diabetic properties. Practically, its application is hindered due to low solubility in aqueous media. Overcoming this challenge, aquasomes can offer an effective approach for delivering drugs and bioactive molecules to target various diseases. The study aimed to develop and evaluate baicalein-loaded aquasomes for improving solubility and comparing their antidiabetic properties to acarbose through in silico docking. Baicalein-loaded aquasomes were prepared through a three-step process: core preparation, lactose coating, and drug loading. The evaluation included assessing particle size, drug-excipient interactions, drug entrapment efficiency, loading capacity, in vitro drug release, and the kinetics of drug release. In silico docking and in vitro α-amylase inhibition activity was evaluated to assess the anti-diabetic potential of baicalein. The baicalein-loaded aquasomes were spherical with sizes ranging from 300-400 nm. FTIR analysis indicated no interaction between the components. The formulation exhibited drug entrapment efficiency of 94.04±0 4.01% and drug loading of 17.60 ± 01.03%. Drug release study showed sustained and complete (97.30 ± 02.06 %) release, following first-order kinetics. Docking analysis revealed comparable binding affinity to acarbose, while the α-amylase inhibition assay showed greater inhibition potential of the aquasomes compared to the baicalein solution. Aquasomes offer an alternative approach to conventional delivery methods. The selfassembling characteristics of aquasomes greatly simplify their preparation process, adding to their appeal as a drug delivery system.

50570 Irritation and sensitization potential of approved topical and transdermal delivery systems – A retrospective study

50570 Irritation and sensitization potential of approved topical and transdermal delivery systems – A retrospective study