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Abstract Background TPN infusions are usually administered during a treatment period of 10–24 hours per day due to the metabolic capacity of the liver. During this time interval physicochemically stable TPN solution (emulsion) is needed for the treatment. The purpose of the present study was to examine how the kinetic stability features of ready-made total parenteral nutrition admixtures containing olive oil and soybean oil will change under the usage-modeling 24-hour application with and without overdose Ca2+. Methods Particle size analysis and zeta potential measurements were carried out to evaluate the possible changes in the kinetic stability of the emulsions. Results Our results indicate that in two of the four mixtures bimodal droplet-size distribution figures were detected and appearance of fat particles over 5 μm can not be disclosed. The tendency for separation of large diameter droplets in the two types of oil-based emulsion systems was different. In case of soybean containing emulsion second peak of droplets appeared in the bottom of the container in contrast to the olive oil containing emulsions where the second peak appeared in the surface layer. Interestingly this phenomenon is independent of calcium-content. Conclusions From therapeutic point the emulsions of the bigger droplets containing upper layer are safer because the potentially dangerous big droplets could remain in the infusion bag after the administration.

Abstract: The purpose of the present study was to formulate a novel thermoresponsive membrane controlled therapeutic system from Metolose® for possible transdermal application. Metolose® gel shows thermal gelation property, which can be characterized by two (T 1, T 2) temperatures. A sharp decrease of viscosity can be measured at T 1, but gelation can be observed at T 2. Different types of Metolose® polymers were compared considering their thermoresponsive behaviour. Only thermal gelation was observed in the case of Metolose® SM, while Metolose® SH showed a sudden decrease of viscosity at T 1. Since this temperature is above the body temperature, so it should be shifted to the skin temperature in case of possible transdermal application. Modulation of thermoresponsibility was followed by rheological method, and the thermoresponsive drug release from Metolose® gel was studied by static liberation test. Our results demonstrated that the effect of different salts (NaCl, NaHCO3, KCl) of various concentrations in Metolose® SH gel reduced T 1 to the skin temperature, which enabled enhanced drug release. [Copyright &y& Elsevier]

Due to their small size, flexibility, and adhesive properties, extracellular vesicles (EVs) hold promises as effective drug delivery systems. However, challenges such as the variability in vesicle types and the need to maintain their integrity for medical applications exist. Curcumin, a compound found in turmeric and known for its diverse health benefits, including anti-cancer and anti-inflammatory properties, faces obstacles in clinical use due to issues like low solubility, limited absorption, and rapid breakdown in the body. This study aimed to incorporate large-sized curcumin-loaded extracellular vesicles (lEVs) into fast-dissolving nanofibers made of poly(vinyl alcohol) (PVA) by electrospinning. By using aqueous PVA-based solutions for electrospinning, the presence of curcumin-loaded lEVs in the nanofibers was confirmed by confocal laser scanning microscopy. Furthermore, the release study demonstrated high concentrations of the drug in nanofibers containing lEVs. These findings are significant for advancing the development and utilization of active ingredient-loaded EV systems within nanofibrous formulations, potentially leading to improved patient outcomes., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: This study investigates combining 3D printing with traditional compression methods to develop a multicomponent, controlled-release drug delivery system (DDS). The system uses osmotic tablet layers and a semipermeable membrane to control drug release, similar to modular Lego® structures., Methods: The DDS comprises two directly compressed tablet layers (push and pull) and a semipermeable membrane, all contained within a 3D-printed frame. The membrane is made from cellulose acetate and plasticizers like glycerol and propylene glycol. Various characterization techniques, including Positron Annihilation Lifetime Spectroscopy (PALS), were employed to evaluate microstructural properties, wettability, morphology, and drug dissolution., Results: Glycerol improved the membrane's wettability, as confirmed by PALS. The system achieved zero-order drug release, unaffected by stirring rates, due to the push and pull tablets within the 3D-printed frame. The release profile was stable, demonstrating effective drug delivery control., Conclusion: The study successfully developed a prototype for a controlled-release osmotic DDS, achieving zero-order release kinetics for quinine hydrochloride after 2 h. This modular approach holds potential for personalized therapies in human and veterinary medicine, allowing customization at the point of care.

A novel ophthalmic delivery system utilizing levofloxacin-loaded, preservative-free, nanofiber-based inserts was investigated. Polyvinyl alcohol (PVA) and Poloxamer 407 (Polox)were employed as matrix materials, while hydroxypropyl-beta-cyclodextrin (HP-β-CD) was a solubilizer. The formulations were prepared via electrospinning and characterized for fiber morphology, drug dissolution, cytotoxicity, and antimicrobial activity. Scanning electron microscopy confirmed uniform fibrous structures. Fourier Transform Infrared spectroscopy and X-ray diffraction analyses demonstrated the amorphous state of levofloxacin within the fibers. In vitro dissolution studies revealed a rapid (within 2 min) and complete drug release, with higher HP-β-CD levels slightly delaying the release. Cytotoxicity tests showed increased HP-β-CD concentrations induced irritation, that was mitigated by sodium hyaluronate. The antimicrobial efficacy of the nanofibers was comparable to conventional eye drops, with lower minimum inhibitory concentrations for most tested strains. The nanofibrous formulation prepared from a PVA-Polox-based viscous solution of the drug:CD 1:1 mol ratio, containing 0.4% ( w / w ) sodium hyaluronate) was identified as a particularly promising alternative formulation due to its rapid and complete dissolution, good biocompatibility, and effective antimicrobial properties. Its gelling properties indicate that the residence time on the eye surface can be increased, potentially reducing discomfort and enhancing therapeutic outcomes. The nanofibrous formulations enhanced antimicrobial efficacy, providing a preservative-free alternative that minimizes the potential eye irritation that might occur because of the preservative agent and reduces the administrated dose frequency by extending the drug's retention time on the eye's surface. Subsequently, it improves patients' adherence, which would reflect positively on the bioavailability. The levofloxacin-HP-β-CD nanofibers demonstrate promise as an alternative to traditional eye drops, offering advantages in solubility, stability, and patient compliance for ocular infection treatment.

Nanofibers can be utilized to overcome the challenges faced by conventional ophthalmic formulations. This study aimed to develop and characterize cysteamine (Cys)-loaded nanofiber-based ophthalmic inserts (OIs) as a potential candidate for the treatment of ophthalmic cystinosis using water-soluble polyvinyl alcohol (PVA)/poloxamer 407 (PO-407) and water-insoluble tetraethoxysilane (TEOS)/PVA nanofibers. Plain and Cys-loaded fibers in different proportions were prepared by the electrospinning method and studied for their morphological, physicochemical, release study, cytocompatibility effects, and stability study. The fiber formation was confirmed by scanning electron microscopy, while Fourier transform infrared spectra showed the most critical peaks for the Cys and the excipients. The release of the Cys was fast from the two polymeric matrices (≤20 min). The release from TEOS/PVA nanofibers is characterized by Case II transport (0.75 < β < 1), while the release from PVA/PO-407 nanofibers follows Fickian diffusion (β < 0.75). The cytocompatibility of compositions was confirmed by hen eggs tested on the chorioallantoic membrane (HET-CAM) of chick embryos. All formulations remained stable under stress conditions (40 ± 2 °C, 75 ± 5% relative humidity) regarding morphology and physicochemical characteristics. The developed nanofibrous mats could be an excellent alternative to available Cys drops, with better stability and convenience of self-administration as OIs.

This systematic review offers a comprehensive analysis of plant-derived extracellular vesicles (PDEVs) as emerging drug delivery systems, focusing on original research articles published between 2016 and 2024 that exclusively examine the use of PDEVs for drug delivery. After a rigorous search across multiple databases, 20 relevant studies out of 805 initial results were selected for analysis. This review systematically summarizes the critical data on PDEV components, isolation methods, and drug-loading techniques. It highlights the potential of PDEVs to significantly enhance drug safety and efficacy, reduce dosage and toxicity, and align drug development with sustainable and environmentally friendly biotechnological processes. This review also emphasizes the advantages of PDEVs over mammalian-derived vesicles, such as cost-effectiveness, higher yield, and reduced immunogenicity. Additionally, it explores the synergistic potential between encapsulated drugs and bioactive compounds naturally present in PDEVs. This study acknowledges the challenges in standardizing isolation and formulation methods for clinical use. Overall, this review provides valuable insights into the current state and future directions of PDEV-based drug delivery systems, highlighting their promising role in advancing pharmaceutical research and development.

The global impact of drug shortages on healthcare systems is a concerning issue that needs urgent attention. These shortages not only jeopardize patient care, public health, and healthcare delivery but also pose distinct challenges for pediatric populations due to their specific medication requirements and vulnerabilities. It is imperative to address this issue to safeguard the health and wellbeing of this specific age group. This review Gaimed to conduct a systematic analysis of strategies for addressing drug shortages in pediatric care from 2014 to 2024. The search included five databases: PubMed, Reaxys, Embase, Scopus, and Science Direct, using the keywords "drug shortage" and "pediatric". The final protocol was developed following the guidelines outlined in the " The PRISMA 2020 statement: An updated guideline for reporting systematic reviews". In total, 234 publications were identified. After screening the search results and applying inclusion and exclusion measures, a total of 27 original research papers were included. The primary finding indicates that a comprehensive approach rooted in risk management can significantly mitigate drug shortages in pediatric settings. This approach should address underlying causes such as manufacturer and delivery challenges and focus on prevention through enhanced forecasting and vigilant shortage monitoring. The most prevalent response involved seeking alternative treatment options. It is imperative to implement institutional and national guidelines, foster communication, and provider education, and minimize waste to effectively mitigate drug shortages in pediatric settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rosário, Hankó and Zelkó.)