Efficient Drug Delivery Research Articles

Exploring Protein-Based Carriers in Drug Delivery: A Review.

Drug delivery systems (DDSs) represent an emerging focus for many researchers and they are becoming progressively crucial in the development of new treatments. Great attention is given to all the challenges that a drug has to overcome during its journey across barriers and tissues and all the pharmacokinetics modulations that are needed in order to reach the targeting sites. The goal of these pathways is the delivery of drugs in a controlled way, optimizing their bioavailability and minimizing side effects. Recent innovations in DDSs include various nanotechnology-based approaches, such as nanoparticles, nanofibers and micelles, which provide effective targeted delivery and sustained release of therapeutics. In this context, protein-based drug delivery systems are gaining significant attention in the pharmaceutical field due to their potential to revolutionize targeted and efficient drug delivery. As natural biomolecules, proteins offer distinct advantages, including safety, biocompatibility and biodegradability, making them a fascinating alternative to synthetic polymers. Moreover, protein-based carriers, including those derived from gelatin, albumin, collagen, gliadin and silk proteins, demonstrate exceptional stability under physiological conditions, and they allow for controlled and sustained drug release, enhancing therapeutic efficacy. This review provides a comprehensive overview of the current trends, challenges, and future perspectives in protein-based drug delivery, focusing on the types of proteins adopted and the techniques that are being developed to enhance their functionality in terms of drug affinity and targeting capabilities, underscoring their potential to significantly impact modern therapeutics.

Modulating the Mucosal Drug Delivery Efficiency of Polymeric Nanogels Tuning their Redox Response and Surface Charge

AbstractMucus is a hydrated, viscoelastic, and adhesive gel that lubricates and protects the body from pathogens; however, its protective function hinders drug/nanomedicine diffusion and treatment efficiency. Therefore, novel drug delivery strategies are required to overcome challenging mucosal barriers. Here, multi‐responsive nanogels (NGs) are developed and explored their interaction with mucus. Specific NG features (e.g., surface charge, temperature responsiveness, and redox response) are evaluated in a typical mucus‐associated environment (i.e., mucin proteins and high glutathione concentrations). The results demonstrate that biocompatibility and the capacity to deliver a protein through mucosal barriers in different in vitro and in vivo models highlight the importance of specific NG design elements. Disulfide bonds are highlighted as redox‐sensitive cross‐linkers within the NG structure as critical for drug delivery performance; they function as degradation points that enable NG degradation and subsequent drug release and anchoring points to adhere to mucin, thereby enhancing their residence time at the desired site of action. Additionally, it is confirmed that surface charges impact interactions with mucin; positively charged NGs exhibit improved interactions with mucin compared to negatively charged and neutral NGs. Overall, the findings underline the importance of redox response and surface charge in NG design for reaching efficient mucosal drug delivery.

Natural Food Components as Biocompatible Carriers: A Novel Approach to Glioblastoma Drug Delivery.

Efficient drug delivery methods are crucial in modern pharmacotherapy to enhance treatment efficacy, minimize adverse effects, and improve patient compliance. Particularly in the context of glioblastoma treatment, there has been a recent surge in interest in using natural dietary components as innovative carriers for drug delivery. These food-derived carriers, known for their safety, biocompatibility, and multifunctional properties, offer significant potential in overcoming the limitations of conventional drug delivery systems. This article thoroughly overviews numerous natural dietary components, such as polysaccharides, proteins, and lipids, used as drug carriers. Their mechanisms of action, applications in different drug delivery systems, and specific benefits in targeting glioblastoma are examined. Additionally, the safety, biocompatibility, and regulatory considerations of employing food components in drug formulations are discussed, highlighting their viability and future prospects in the pharmaceutical field.

Anti-aging Metabolite-Based Polymeric Microparticles for Intracellular Drug Delivery and Bone Regeneration.

Alpha-ketoglutarate (AKG), a key component of the tricarboxylic acid (TCA) cycle, has attracted attention for its anti-aging properties. Our recent study indicates that locally delivered cell-permeable AKG significantly promotes osteogenic differentiation and mouse bone regeneration. However, the cytotoxicity and rapid hydrolysis of the metabolite limit its application. In this study, we synthesize novel AKG-based polymeric microparticles (PAKG MPs) for sustained release. In vitro data suggest that the chemical components, hydrophilicity, and size of the MPs can significantly affect their cytotoxicity and pro-osteogenic activity. Excitingly, these biodegradable PAKG MPs are highly phagocytosable for nonphagocytic pre-osteoblasts MC3T3-E1 and primary bone marrow mesenchymal stem cells (BMSCs), significantly promoting their osteoblastic differentiation. RNAseq data suggest that PAKG MPs strongly activate Wnt/β-catenin and PI3K-Akt pathways for osteogenic differentiation. Moreover, PAKG enables poly (L-lactic acid) and poly (lactic-co-glycolic acid) MPs (PLLA & PLGA MPs) for efficient phagocytosis. Our data indicate that PLGA-PAKG MPs-mediated intracellular drug delivery can significantly promote stronger osteoblastic differentiation compared to PLGA MPs-delivered phenamil. Notably, PAKG MPs significantly improve large bone regeneration in a mouse cranial bone defect model. Thus, the novel PAKG-based MPs show great promise to improve osteogenic differentiation, bone regeneration, and enable efficient intracellular drug delivery for broad regenerative medicine.

A review on nanotechnological aspects in medicinal textile

<p><span lang="EN-US" style="font-size: 10.0pt; line-height: 115%; font-family: 'Times New Roman',serif; mso-fareast-font-family: Calibri; color: windowtext; mso-ansi-language: EN-US; mso-fareast-language: EN-US; mso-bidi-language: AR-SA;">Nanoscience and Technology has become popular and touched almost every branch of science and technology. Textile engineering is also not exception. Various nanoparticles are being used in smart textiles and technical textile products. Medical textile is an important area and have much opportunities for innovation and discoveries. Therefore, nanomaterials are used in medical textiles to have exotic properties. Herein we have discussed several methods for the characterization of materials at nanoscale. The common spectroscopic techniques like UV-Visible spectroscopy and microscopic techniques like scanning electron microscopy and transmission electron microscope routinely used in material characterization are discussed in detail. In the last section of the article we discussed various applications of nanomaterials in modern medical textile. The nanomaterials are used in surgical gowns, sanitary napkins, UV protection appliances, antimicrobial coating, sutures etc. Some advanced nanomaterials can be used in disease diagnosis, flame retardants, efficient drug delivery systems etc.</span></p>

Enhancement of Temozolomide Stability and Anticancer Efficacy by Loading in Monopalmitolein-Based Cubic Phase Nanoparticles.

Temozolomide (TMZ) is a prodrug possessing a wide spectrum of anticancer activities. TMZ is pharmacologically inactive, but at a physiological pH, it is quickly converted to an active metabolite, 5-aminoimidazole-4-carboxamide, and a methyldiazonium cation. Due to its chemical nature, TMZ presents some capability of crossing the blood-brain barrier and therefore is used as a first-line agent in the treatment of gliomas. Here, we aimed to improve the anticancer effectiveness of TMZ by loading it into cubosomes, which are lipid nanoparticles recognized as efficient nano-based drug delivery systems. TMZ was incorporated into the monoolein (MO)- and monopalmitolein (MP)-derived cubic phases to improve its stability and half-life. It was considered that the drug release rate may vary between the MO and MP cubosomes, as the water channels of MP phases are larger than those of MO cubosomes. Therefore, we expected that due to the MPs' ability to entrap more drug molecules inside the mesophase, the concentration of TMZ available to cancer cells would be enhanced. This assumption was supported by biological analyses using the A-172 and drug-resistant T98G glioma-derived cell lines. The strongest reduction in viability was observed for A-172 cells treated with TMZ-loaded MP nanoparticles. Importantly, the TMZ-loaded MPs also caused a significant anticancer effect in the drug-resistant T98G glioma-derived cells. Both MO and MP empty cubic phases did not affect the survival of the tested cells. Concluding, TMZ-loaded cubosomes present strong anticancer properties. Encapsulating the drug within the lipid nanostructure helps to protect the drug from degradation and allows for greater accumulation of TMZ at the tumor site. Together with chemical-based features of mesophases related to increased cargo size and kinetic properties, we imply that MPs may be considered as a highly efficient nano-based drug delivery system to treat poorly curable tumors including gliomas.

Flow and heat transfer of non-miscible micropolar and Newtonian fluid in porous channel sandwiched between parallel plates

An analytical approach has been considered to inspect the flow and heat transfer of immiscible Newtonian and micropolar fluid in a porous medium. This study aims to elucidate the Darcy effect on the model in which isotropic porous regions with different permeability are used. The model of the current problem explains that the flow region is divided into two regions: Newtonian fluid flows in the upper layer, and micropolar fluid flows in the lower layer. Different constant temperatures imposed at boundary walls, heat transfer does not affect the pressure gradient. The governing equations are solved analytically by applying a linear differential equation (LDE). The effect of associated physical parameters such as material parameter, Darcy number, Eckert number, Prandtl number, and viscosity ratio on velocity, micro-rotation, heat transfer, flow rate, heat transfer rate, wall shear stress, and Nusselt number have been inspected. The most significant finding of this research work is that increasing the Darcy number signifies enhanced permeability, resulting in a higher flow rate. The heat transfer rate at the top occurs maximum when the material parameter’s range is minimum while raising the viscosity ratio leads to an increasing heat transfer rate at the bottom. Enhancement in material parameter influences Nusselt number and decreases in nature. The findings of our study are verified with the previously established results. The present work has a setup that is useful in petroleum extraction, transport problems in reservoir rock of an oil field, improving nutrient transport and thermal regulation in tissue engineering, and designing more efficient drug delivery systems and biomedical devices.

Synthesis of pH-sensitive polymeric micelle drug carries for potential cancer chemotherapy applications

Alpha mangostin, a natural xanthone derivative from mangosteen fruit pericarp, exhibits antiproliferative and apoptotic effects on different cancer cells by inhibiting cell cycle progression, inducing apoptosis, and modulating signaling pathways. However, this candidate is limited in medical treatment due to the poor water solubility. Nanoparticles have emerged as promising drug delivery systems to improve drug delivery efficiency but one of the problem of nanoparticles is the capability of endosomal escape. Therefore, pH-sensitive polymer nanosystems were utilized for targeted drug delivery, and enhanced efficacy by offering controlled release and endosomal escape capabilities. This study aimed to synthesize PEG- P(Asp-Hyd-Man) copolymer and create micelle for alpha mangostin delivery. The micelles were measured with particle size average of 80.2 ± 15 nm, and the PDI of 0.17. Additionally, the release behavior of alpha mangostin was examined in vitro that show pH-sensitive polymeric micelles rapidly release at pH 5.0 compared with the arterial pH 7.4. The findings of this study are significant in the development of an effective drug delivery system using alpha mangostin and other therapeutic agents.

Drug Delivery and Monitoring through Wearable Devices with Microneedles in the Field of the Health Care System

: Microneedles represent a revolutionary advancement in drug delivery and diagnostics, offering a minimally invasive approach to accessing the intricate biological environment of the human body. These micron-sized needles, typically ranging from 25 to 1000 micrometers in length, penetrate the outermost layer of the skin, creating microchannels that facilitate the transdermal administration of therapeutics or the extraction of interstitial fluid for analysis. This innovative technology holds great promise for enhancing patient compliance, reducing side effects, and improving the overall efficiency of drug delivery. Integrating microneedles with wearable devices further amplifies their potential impact. Wearable devices provide a seamless interface for monitoring and controlling microneedle-based systems, fostering real-time data collection and personalized healthcare. Such devices can be designed to administer precise drug doses at predetermined intervals, adapting treatment regimens to individual patient needs. : Additionally, the combination of microneedles and wearable devices enables continuous monitoring of biomarkers through the extraction of interstitial fluid, offering a non-invasive method for disease diagnosis and management. The review also provides a detailed overview of the mechanisms, types, fabrication techniques, applications, and patents for integrating microneedles with wearable devices. This symbiotic relationship between microneedles and wearables opens new paths for patient-centric healthcare, with the potential to transform chronic disease management and streamline therapeutic interventions. As these technologies continue to evolve, their integration may pave the way for personalized, on-demand healthcare solutions, accompanying a new era of patient well-being and treatment efficacy.

A biomimetic targeted nanosystem delivering synergistic inhibitors for glioblastoma immune microenvironment reprogramming and treatment

Efficient drug delivery across the blood-brain barrier is imperative for treating glioblastoma (GBM). This study utilized the GBM cell membrane to construct a biomimetic targeted nanosystem (GMNPs@AMD/RAPA) that hierarchically releases the CXCR4 antagonist AMD3100 and the mTOR pathway inhibitor rapamycin (RAPA) for reprogramming the tumor immune microenvironment and suppressing the progression of GBM. By initially inhibiting the CXCL12/CXCR4 axis, the tumor microenvironment (TME) was reprogrammed to enhance the infiltration of cytotoxic T lymphocytes (CTLs) into the TME while suppressing tumor cell survival, proliferation, and angiogenesis. Subsequently, through further cellular uptake and degradation of the nanoparticles, the mTOR pathway inhibitor RAPA was released, further suppressing the tumor progression. This study successfully combined chemotherapy and immunotherapy, achieving effective synergistic therapeutic effects, and suppressing the progression of GBM.

Chemically Powered Nanomotors with Magnetically Responsive Function for Targeted Delivery of Exosomes.

Janus structure plays a crucial role in achieving chemically driven nanomotors with exceptional motion performance. However, Janus-structured chemically driven nanomotors with magnetic responsiveness are commonly fabricated by sputtering metal films. In the study, a self-assembly technique is employed to asymmetrically modify the surfaces of magnetic silica (SiO2@Fe3O4) nanoparticles with platinum nanoparticles, resulting in the formation of this kind nanomotors. Compared to platinumfilm, platinum nanoparticles exhibit a larger surface area and a higher catalytic activity. Hence, the nanomotors demonstrate improved diffusion capabilities at a significantly lower concentration (0.05%) of hydrogen peroxide (H2O2). Meanwhile, exosomes have gained attention as a potential tool for the efficient delivery of biological therapeutic drugs due to their biocompatibility. However, the clinical applications of exosomes are limited by their restricted tropism. The previously obtained nanomotors are utilized to deliver exosomes, greatly enhancing its targetability. The drug doxorubicin (DOX) is subsequently encapsulated within exosomes, acting as a representative drug model. Under the conditions of H2O2 concentration at the tumor site, the exosomes exhibited a significantly enhanced rate of entry into the breast cancercells. The utilization of the nanomotors for exosomes presents a novel approach in the development of hybrid chemically and magnetically responsive nanomotors.

Key Challenges, Influencing Factors, and Future Perspectives of Nanosuspensions in Enhancing Brain Drug Delivery.

Many brain diseases pose serious challenges to human life. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common neurodegenerative diseases that seriously threaten human health. Glioma is a common malignant tumor. However, drugs cannot cross physiological and pathological barriers and most therapeutic drugs cannot enter the brain because of the presence of the Blood-brain Barrier (BBB) and Bloodbrain Tumor Barrier (BBTB). How to enable drugs to penetrate the BBB to enter the brain, reduce systemic toxicity, and penetrate BBTB to exert therapeutic effects has become a challenge. Nanosuspension can successfully formulate drugs that are difficult to dissolve in water and oil by using surfactants as stabilizers, which is suitable for the brain target delivery of class II and IV drugs in the Biopharmaceutical Classification System (BCS). In nanosuspension drug delivery systems, the physical properties of nanostructures have a great impact on the accumulation of drugs at the target site, such as the brain. Optimizing the physical parameters of the nanosuspension can improve the efficiency of brain drug delivery and disease treatment. Therefore, the key challenges, influencing factors, and future perspectives of nanosuspension in enhancing brain drug delivery are summarized and reviewed here. This article aims to provide a better understanding of nanosuspension formulation technology used for brain delivery and strategies used to overcome various physiological barriers.

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.

53976 Topical in-vitro delivery of a model drug from novel silicone polymer gel formulations providing efficient drug delivery and pleasant aesthetics

53976 Topical in-vitro delivery of a model drug from novel silicone polymer gel formulations providing efficient drug delivery and pleasant aesthetics

Development and characterization of a zeolite based drug delivery system: Application to cannabidiol oral delivery

The growing interest in the therapeutic potential of cannabidiol (CBD) has led to the need for effective and reliable delivery methods that overcome its low oral absorption. Zeolites, a class of porous nanoparticles, offer unique advantages as drug carriers due to their high surface area and adjustable pore size. In this study, a zeolite-based drug delivery system was developed for the encapsulation of CBD. The zeolite particles were characterized using various techniques such as Scanning Electron Microscopy (SEM), N2 adsorption analysis, Solid-state Fourier Transform Infrared (FTIR), Direct Light Scattering (DLS), X-ray diffraction (XRD) and thermogravimetric analysis (TGA) before and after the loading. The drug encapsulation efficiency, and the release profile of CBD from the zeolite matrix were evaluated in addition to in vitro dissolution experiments in the intestinal and gastric simulated fluids. The results showed that the loaded zeolite particles exhibited high encapsulation efficiency of 73.5 %. XRD analysis proved that the USY structure remained intact after loading with CBD. DLS and N2 adsorption analysis indicated that CBD was successfully loaded into the zeolite matrix. When compared to CBD containing particles in a commercialized capsule, the in-vitro dissolution rate of CBD loaded zeolite was significantly higher after 30 min in the simulated stomach (pH 1.8) and the intestinal (pH 6.8) fluids, 67.8 % versus 43.6 % and 62.6 % vs 38.4 % respectively. Our findings open new avenues for the use of zeolites as an efficient drug delivery system for drugs with low bioavailability like CBD.

Adaptive Size Evolution of an MOFs-in-MOF Nanovehicle for Enhanced Nucleus-Targeted Tumor Chemotherapy.

A metal-organic frameworks (MOFs)-in-MOF nanovehicle (160 nm), which was constructed with newly prepared ultrasmall Cu(I)Cu(II)-BTC MOFs (UCMs, 2.95 nm) loaded with doxorubicin (DOX) and a nuclear localization signal (NLS) peptide as multicores (UCMDNs) and ZIF-8 as the shell MOF, was proposed to cross layers of biological barriers with adaptive size evolution capacity for achieving efficient nucleus-targeted drug delivery. It first enhanced tumor tissue penetration through its larger nanosize effect. Then the acidic tumor environment made the ZIF-8 shell degrade, releasing small-sized UCMDNs to enter into the cell and into the nucleus under the guidance of NLS. Furthermore, due to the distinct surface structural characteristics of UCMs, UCMDNs remained stable in the cytoplasm and collapsed in the nucleus due to the DOX-DNA interaction to deliver DOX precisely. It showed superior performance in the nucleus-directed delivery of DOX (delivery efficiency up to 56.7%) and a high tumor growth inhibition rate (96.4%), offering promising prospects in tumor chemotherapy.

Modulation of blood-tumor barrier transcriptional programs improves intra-tumoral drug delivery and potentiates chemotherapy in GBM.

Glioblastoma (GBM) is the most common malignant primary brain tumor. GBM has an extremely poor prognosis and new treatments are badly needed. Efficient drug delivery to GBM is a major obstacle as the blood-brain barrier (BBB) prevents passage of the majority of cancer drugs into the brain. It is also recognized that the blood-brain tumor barrier (BTB) in the growing tumor represents a challenge. The BTB is heterogeneous and poorly characterized, but similar to the BBB it can prevent therapeutics from reaching effective intra-tumoral doses, dramatically hindering their potential. Here, we identified a 12-gene signature associated with the BTB, with functions related to vasculature development, morphogenesis and cell migration. We identified CDH5 as a core molecule in this set and confirmed its over-expression in GBM vasculature using spatial transcriptomics of GBM patient specimens. We found that the indirubin-derivative, 6-bromoindirubin acetoxime (BIA), could downregulate CDH5 and other BTB signature genes, causing endothelial barrier disruption in endothelial monolayers and BBB 3D spheroids in vitro. Treatment of tumor-bearing mice with BIA enabled increased intra-tumoral accumulation of the BBB non-penetrant chemotherapeutic drug cisplatin and potentiated cisplatin-mediated DNA damage by targeting DNA repair pathways. Finally, using an injectable BIA nanoparticle formulation, PPRX-1701, we significantly improved the efficacy of cisplatin in patient-derived GBM xenograms and prolonged their survival. Overall, our work reveals potential targets at the BTB for improved chemotherapy delivery and the bifunctional properties of BIA as a BTB modulator and potentiator of chemotherapy, supporting its further development.

Magnetized electroosmotic drug delivery of Au-SiO2 nanocarriers through blood-based jeffrey hybrid nanofluid in a microchannel: Caputo Fabrizio derivative modeling

Fractional calculus is emerging as a promising field to overcome the intricacies inherent in biological systems that prevent conventional techniques from producing optimal results. The present research emphasizes the impact of thermal radiation, chemical reactions, and radiation absorption on an electroosmotic magnetohydrodynamic (MHD) blood-based Jeffrey hybrid nanofluid flow in a microchannel, employing the novel Caputo-Fabrizio fractional calculus approach. This study is carried out on two models: ramped and constant boundary conditions with distinct zeta potentials. The graphs are drawn with the help of MATLAB software. Our results demonstrate that the fractional order significantly influences the drug dispersion, and for α=0.9 (fractional parameter), the blood flow becomes wavy. The presence of nanoparticles improves drug transport, hence enhancing the drug concentration in proximity to the target site. For α=0.1, the Jeffrey nanofluid with ramped conditions shows the highest velocity enhancement in the case of pressure-driven, natural convective flow. Electroosmotic force facilitates fluid flow and enhances drug transport efficiency. For Ha < 4, the blood velocity decreases in the vicinity of the plate y = 0, and reverse behavior is observed as it passes y = 0.5, which can aid in effective drug delivery. At y = 0, the heat transfer rate increases by a maximum of 199.18 % while skin friction decreases to 3.07 %, aiding in maintaining medications at the desired temperature and improving drug delivery efficiency. The temperature and velocity of the blood hybrid nanofluid are maximized under ramping wall settings compared to constant wall conditions.

Treatment of endophthalmitis using a novel methacrylic anhydride-modified hydroxypropyl methylcellulose hydrogels loaded with S-nitrosoglutathione: An ex-vivo keratitis model

Introductionpost-operative endophthalmitis (POE) following cataract surgery remains a significant concern due to its impact on vision and the associated socio-economic burden. S-Nitrosoglutathione (GSNO) shows promise due to its stability and antimicrobial properties. Hydroxypropyl methylcellulose (HPMC) is commonly used in eye drops for drug retention, while methacrylic anhydride (MA) modification enhances adhesion. In our study, we aimed to develop a novel GSNO-loaded HPMC-MA hydrogel, and used an ex-vivo corneal keratitis model to test the anti-inflammatory and anti-microbial effects of HPMC-MA hydrogels containing GSNO. Additionally, the study evaluated the irritative potential of the eye drop formulation containing GSNO-loaded HPMC-MA hydrogels on rabbit eyes. MethodWe prepared and tested the GSNO-loaded HPMC-MA hydrogels characters. Fourier Transform Infrared (FTIR) spectroscopy measurement to verify modification, cell viability assays, osmolality tests, in-vivo ocular irritation assessments, inflammatory cells genes expression using RT-PCR, bacterial concentration analysis with an ex-vivo S. aureus keratitis model were conducted. ResultsFTIR spectroscopy confirmed successful MA modification and GSNO incorporation. Cell viability experiments suggested optimal GSNO concentration at 80 μM. Osmolality tests indicated no significant changes in osmolality post-modification. Ocular irritation tests on rabbits showed no adverse reactions. In the ex-vivo keratitis model, GSNO-HPMC-MA reduced inflammation and inhibited bacterial growth, as reflected in gene expression and bacterial concentration analyses. ConclusionThe study demonstrates the successful development of GSNO-loaded HPMC-MA hydrogels with potential as a topical formulation for endophthalmitis treatment. This novel approach shows promise in addressing challenges related to drug delivery efficiency and antimicrobial efficacy in ocular infections.

The effect of decoupling humidity control on aerosol drug delivery during HFNC for infants.

Aerosol therapy is commonly used during treatment with high-flow nasal cannula (HFNC) in the intensive care unit (ICU). Heated humidification inside the HFNC tubing circuit leads to unwanted condensation, which may greatly limit the efficiency of drug delivery. In this study, we aimed to investigate whether a novel humidification system, which decouples temperature and humidity control, can improve the delivered dose. In a bench study setup, fluorescein sodium solution was nebulized using a vibrating-mesh nebulizer in an infant HFNC circuit to measure the delivered dose, with a conventional versus a novel decoupled humidifier. The deposition of fluorescein inside each breathing circuit component and a final collection filter at the end of the nasal cannula was collected and quantified with a UV-vis spectrometer. Droplet sizes at different sections of the breathing circuit were measured by laser diffraction. Three air flow rates: 5, 10 and 15 L/min, and two nebulizer positions: (1) at the humidifier and (2) after the inspiratory tube, were tested. The delivered dose decreased with increasing flow rate for the conventional setup and was higher when the nebulizer was placed after the inspiratory tube. Turning off the conventional humidifier 10 minutes before and during nebulization did not improve the delivered dose. The decoupled humidifier achieved a significantly higher (p = .002) delivered dose than the conventional setup. The highest delivered dose obtained by the decoupled humidifier was 62.4% when the nebulizer was placed after the humidifier, while the highest dose obtained for the conventional humidifier was 36.3% by placing the nebulizer after the inspiratory tube. In this bench study, we found that the delivered dose for an infant HFNC nebulization setup could be improved significantly by decoupling temperature and humidity control inside the HFNC circuit, as it reduced drug deposition inside the breathing circuit.