Current Issue : July-September Volume : 2026 Issue Number : 3 Articles : 5 Articles
Background: Dry eye disease (DED) is characterized by tear film instability and a hyperosmolar ocular surface, which significantly impacts ocular health. Artificial tear solutions (ATSs) have been effective frontline treatments for DED, yet current commercially available products often provide only temporary relief, necessitating frequent daily administration. Significant efforts have been made to develop next-generation ATSs that can provide prolonged protective effects for DED. High-molecular-weight sodium hyaluronate (HA) is more commonly used in multi-dose preservative ATSs due to its longer chain lengths and rheological properties that can provide an enhanced retention time and clinical comfort and effects. The current methods to evaluate ATSs have largely focused on human biocompatibility and rheological testing and often overlook the dynamic nature of cellular phenotypes or the protective mechanisms at a cellular level. Therefore, this study developed novel in vitro mammalian cell assays involving human corneal epithelial cells (HCECs) to comprehensively assess ATSs with HA for biocompatibility and efficacy. Methods: We evaluated cellular viability across varying severities in two distinct DED models: desiccation and hyperosmotic stress. Simultaneously, time-lapse imaging coupled with computational image analyses quantified subtle, yet significant, cellular morphological changes under these stress condition. Results: Our assays revealed that ATSs provide significant, yet varying, protection against mild, medium, and harsh desiccation stress, as well as hyperosmotic conditions. This study also made a key insight that was the observation that DED conditions induce drastic HCEC morphological changes, including significant cellular monolayer breakage, which were effectively mitigated by the ATS products used in this work. Conclusions: The assays presented here provide a robust standard for ATS testing, ultimately guiding the selection of more effective next-generation therapies and aiding in a greater understanding of DED pathogenesis....
Drug–food interactions may compromise therapeutic efficacy, particularly for life- saving medications such as anticoagulants. Changes in gastric fluid properties, including pH modification and surface film formation, can alter drug dissolution and release. This study evaluated a potential interaction between clopidogrel and spinach and explored the underlying mechanisms. In vitro disintegration and dissolution studies were conducted using HCl and phosphate buffers with and without 5% and 7.5% spinach extract. Drug release was quantified by high- performance liquid chromatography (HPLC), with six media conditions analyzed in triplicate. Disintegration testing was performed in simulated gastric and intestinal fluids and in the presence of spinach leaves to assess the effect of film formation on tablet wetting and disintegration. In vitro–in vivo extrapolation (IVIVE) was assessed using GastroPlus software. Clopidogrel dissolution decreased with increasing spinach concentration in both media. In HCl buffer, dissolution declined from 99% to 94% and 89%, while in phosphate buffer it decreased from 71% to 66% and 56%. These effects were associated with increased pH (HCl: 1.91, 2.83, 2.98; phosphate: 6.81, 8.83, 6.84), increased solution viscosity, 17.63 to 17.67 and 17.70 in HCl buffer, and from 17.44 to 17.50 and 17.54 in phosphate buffer. Moreover, reduced fluid penetration was due to spinach leaves coverage. IVIVE analysis showed weak correlations (R2 = 0.74 in HCl and 0.69 in phosphate buffer). Spinach reduced clopidogrel dissolution in vitro, with statistically significant effects at 5% spinach in HCl buffer (ANOVA test, p- value 0.019) and 7.5% in phosphate buffer (ANOVA test, p- value < 0.001). This interaction appears to be mediated by pH alteration, physical film formation, and potentially metal–drug complexation. Confirmation through in vivo studies is warranted....
Objective: This study assessed the ability of capsule formulations to improve the oral delivery and retain activity of an acid-sensitive enzyme during gastrointestinal transit. Methods: The dissolution characteristics of five capsule formulations—single DRcaps® [DR], single Vcaps® Plus [VCP], and three DUOCAP® capsule-in-capsule combinations, DRcaps® inside DRcaps® (DR-in-DR), DRcaps® inside Vcaps® Plus (DR-in-VCP), and Vcaps® Plus inside DRcaps® (VCP-in-DR)—were evaluated in an in vitro simulation of a healthy human upper gastrointestinal tract under fasting and fed conditions using the Simulator of the Human Intestinal Microbial Ecosystem (SHIME)® platform. Capsules contained caffeine as a marker of capsule dissolution, and pancreatin as an active ingredient for which activity was determined by the conversion of tributyrin. Readouts included visual capsule scoring, the analysis of caffeine release, and the quantification of tributyrin-to-butyrate conversion at the end of each gastrointestinal tract segment. Results: The single VCP capsules had a high level of caffeine release at the end of the stomach incubation with low butyrate recovery (16–21%), suggesting the rapid release and gastric degradation of the unprotected enzyme. The single DR, DR-in-VCP, and VCP-in-DR formulations showed caffeine release at the end of the duodenum and/or jejunum and had high butyrate recovery, ranging from 53% to 87%. The DR-in-DR formulation had the most delayed release, with incomplete caffeine release and low-to-moderate butyrate recovery (10–36%). Conclusions: Fast capsule dissolution led to the reduced enzymatic activity of the active ingredient, while delayed dissolution resulted in inadequate time for the enzymatic conversion of tributyrin to butyrate. These results highlight that capsule selection should align with the intended use and targeted nutrient delivery, with DUOCAP® formulations being best suited for small intestinal (VCP-in-DR and DR-in-VCP) and colonic (DR-in-DR) delivery....
Background/Objectives: Lipid nanoparticles (LNPs) are a prominent example of delivery systems that are used to prevent the degradation of messenger ribonucleic acid (mRNA) and facilitate cell uptake. Improving LNP transfection efficiency requires careful selection of key formulation components, including the ionizable lipid and the coding sequence of the nucleic acid. Therefore, it is crucial to assess various options for the target cells, as results can differ significantly between cell types. Building on previous work investigating the effect of apolipoprotein E4 on LNP transfection of human monocyte-derived dendritic cells, we assess the impact of different ionizable lipids and compare modifications in the mRNA uridine to further optimize the delivery to these cells. Methods: LNPs containing eGFP mRNA with different uridine modifications were produced via microfluidic mixing and investigated for their in vitro transfection efficiency of human monocyte-derived dendritic cells. Transfection occurred in the presence of apolipoprotein E4 for different encapsulated mRNA concentrations. Delta mean fluorescence intensity and eGFP positive cells were measured by flow cytometry 48 h after transfection. Cell viability was assessed via AnnexinV/7-AAD staining, after comparing this method to LIVE/DEADTM Fixable Near-IR staining. Results: This study shows that a combination of SM-102 as the ionizable lipid with eGFP mRNA containing N1-methylpseudouridine enabled the transfection of human monocyte-derived dendritic cells with very high efficiency at low concentrations, allowed for dose sparing, and even led to the LNPs outperforming a specifically tailored electroporation protocol. Conclusions: Improvement of nucleic acid delivery to human monocyte-derived dendritic cells, known for their difficulty to be transfected, was achieved by LNP formulation tuning....
Background/Objectives: Iron deficiency and associated iron deficiency anaemia represent a major global health burden. Parenteral nutrition (PN) patients are at increased risk of iron deficiency due to inadequate iron supplementation. Currently, iron is added to all-in-one (AIO) PN mostly as low-dose ferric chloride in trace element solutions, limited to 1–2 mg in adults, to ensure emulsion stability and prevent lipid peroxidation. The objective of this study was to evaluate the compatibility and stability of selected, widely used complex-bound iron products added to AIO PN over a 48 h period. Methods: Ferric carboxymaltose and iron sucrose were added as non-biological complex intravenous iron oxide carbohydrate products to two different commercial AIO PN admixtures for adults. The iron concentrations used were 100 and 400 mg/L (1.79 and 7.16 mmol/L), corresponding to approximately 200 mg (3.58 mmol) of iron dose per PN bag. Free and complex-bound iron were separated using 100 kDa dialysis tubes. Free and complex-bound iron were assessed at 4, 24, and 48 h after admixing. pH was measured before and at 0, 4, 24, and 48 h after admixture. Iron quantification was performed by inductively coupled plasma mass spectrometry (ICP-MS). Results: No significant changes in complex-bound iron concentration were observed over the 48 h incubation period (p-value = 0.449; estimate 0.060 mg/L per h, 95% CI −0.089, 0.201 mg/L per h). The concentration of free iron was very low and increased only slightly over time. Iron recovery ranged from 95.8% to 103.9%. The addition of the alkaline iron sucrose significantly increased the pH of the AIO admixture (p-value = 0.033), whereas the addition of ferric carboxymaltose did not affect the pH (p-value = 0.351). After the initial increase, the pH of all conditions remained stable over the 48 h incubation period (p-value = 0.07). Conclusions: Ferric carboxymaltose demonstrated stable intravenous iron admixtures within the PN formulations tested. Before the clinical application of these findings, further studies should specifically evaluate the lipid peroxidation and stability of the lipid emulsions, the most sensitive and important PN compatibility and safety characteristics of AIO PN....
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