Supraparticles (SPs) are secondary particles formed through nanoparticle self-assembly with porous architectures and bioinspired structural features suitable for drug delivery applications. Although binder-mediated structural control influences SP assembly, how different loaded drugs systematically alter amyloid nanofibril (ANF) and SP structures remains unclear. In this study, neutral, basic, and acidic model drugs-acetaminophen (ACP), fluconazole (FCZ), and proglumide (PGM), respectively-were incorporated into spray-dried SPs composed of silica nanoparticles (SiNPs) and ANFs to investigate the effects of drug properties on SP structure and release behavior. All drugs exhibited nearly 100% loading efficiency, and powder X-ray diffraction analysis revealed that they were in an amorphous state within the SPs. ACP- and FCZ-loaded SPs maintained their characteristic ANF-induced wrinkled morphology, whereas PGM-loaded SPs exhibited a pronounced loss of wrinkling at pH 2, indicating that acidic drugs can disrupt ANF-mediated assembly during SP formulation. Drug release studies further showed that ANFs suppressed the initial burst release and slowed the overall release by restricting diffusion pathways within the SP structures. This suppression was the most pronounced in PGM-loaded SPs, likely owing to drug retention within the assembled ANF domains. These findings demonstrate that drug acid-base properties critically modulate SP morphology and release behavior, highlighting the importance of drug-biomaterial interactions in designing SP-based delivery platforms.

Percutaneous absorption is essential in the safety assessment of topical drugs and cosmetic products, but the potential impact of skin pigmentation on dermal absorption remains understudied. Here, a novel framework integrating quantitative pigmentation characterization, barrier function assessment, and in vitro permeation testing (IVPT) to investigate the role of melanin in percutaneous absorption using both excised and reconstructed human skin models was established. Abdominal excised human skin (EHS) from female donors of Fitzpatrick phototypes (FP) I/II and FP V/VI and reconstructed human pigmented epidermis (RHPE) with melanocytes derived from Caucasian and African American donors were tested. RHPEs were cultured for 15 days in basal or melanogenesis-stimulating media. Skin pigmentation level, transepidermal water loss (TEWL), and the in vitro permeation of radiolabeled caffeine, salicylic acid, testosterone, mannitol, hydroquinone, and ciprofloxacin were evaluated in EHS and RHPE samples. Melanin quantification assays and histological analyses confirmed higher pigmentation in EHS of FP V/VI versus FP I/II donors, in RHPE from African American versus Caucasian donors, and in RHPEs cultured under melanogenesis-stimulating versus basal conditions, especially in tissues from African American donors. No significant differences in TEWL were observed between EHS groups or across RHPE groups. In general, no statistically significant differences were observed in the cumulative amount, flux, and mass distribution of test chemicals between EHS groups or across RHPE groups. The study demonstrated the feasibility of using a standardized toolkit and pigmented human skin models to investigate the role of melanin in percutaneous absorption in vitro. The ability to modulate pigmentation levels in RHPEs within the same donor background supports their utility as a reproducible model for evaluating melanin-associated variability in dermal safety assessments, particularly for compounds that may interact with melanin.

Poisoning by acetaminophen is a serious public health concern because of its accessibility and the ease with which overdoses can occur accidentally or on purpose. The liver metabolizes acetaminophen, and when taken in excess, it is transformed into a poisonous metabolite that seriously damages the liver and may result in hepatic failure and death. The cornerstone of treatment is the early administration of N-acetylcysteine, which is most effective within 8 hours of ingestion. Co-ingestants, therapy timing, and pre-existing liver diseases are some of the factors that affect toxicity. Both unintentional overdoses and deliberate poisonings have legal and forensic ramifications, especially where minors or self-harm are involved. In fatal cases, a toxicological investigation is essential to identify the cause of death and differentiate acetaminophen poisoning from other possible causes. Regulations such as age restrictions, pack-size constraints, and improved labeling have demonstrated the potential to reduce the prevalence of acetaminophen toxicity. Intentional and accidental overdoses can be avoided in part by raising public awareness and educating healthcare professionals. To lessen the impact of acetaminophen poisoning on public health systems, more research is required to enhance early identification, improve treatment techniques, and guide policy decisions. This review aims to familiarize clinicians and forensic professionals with the pharmacology, clinical presentation, management, and medicolegal aspects of acetaminophen toxicity..

Achieving a uniform powder mixture in low-dose and complex formulations is inherently challenging and can undermine downstream process performance and product quality. This study aimed to assess the extent to which twin-screw wet granulation (TSWG) can mitigate upstream blend variability caused by short and less intensive mixing conditions. Two low-dose formulations, containing either a highly water-soluble (metformin.HCl) or a sparingly water-soluble (caffeine anhydrous powder) Active Pharmaceutical Ingredient (API), were studied. Granulator parameters, including liquid-to-solid (L/S) ratio and screw speed, were evaluated using a two-factor screening design to identify conditions yielding the most uniform API concentration across different granule sizes. To assess the impact of semi-continuous blender parameters on blend uniformity, impeller speed, blending time, and fill level were systematically varied using a central composite orthogonal (CCO) design. Subsequently, blends exhibiting progressively increasing relative standard deviation (RSD) values were granulated to evaluate how upstream blend uniformity affects downstream API distribution. High L/S ratios and screw speeds narrowed the granule size distribution and improved API distribution across granule size fractions. Blend uniformity improved with increasing blending time and impeller speed, whereas higher fill levels reduced mixing performance. For the investigated formulations, no statistically significant changes in API concentration across different granule sizes were observed at blend RSD levels up to 9.2% for the metformin.HCl formulation and 3.0% for the caffeine formulation. These findings demonstrate that TSWG can compensate for moderate up-stream variability, highlighting its potential to enable robust continuous manufacturing of low-dose formulations at high throughput.

Idiopathic hypersomnia (IH) is a chronic central disorder of hypersomnolence characterized by excessive daytime sleepiness despite adequate or prolonged sleep, with potentially substantial effects on occupational functioning, cognition, and driving safety. Pharmacologic management may be challenging when treatment is limited by inadequate efficacy or adverse effects. We report a young woman with severe hypersomnolence and a diagnosis of IH supported by clinical history and objective sleep testing. Multiple sleep latency testing demonstrated a mean sleep latency of one minute and 22 seconds, with no sleep-onset rapid eye movement periods (SOREMPs). Her Epworth Sleepiness Scale (ESS) score was 18/24, and symptoms included prolonged sleep duration, extended daytime naps, occupational impairment, and drowsy driving. Modafinil initially produced substantial benefit but subsequently lost efficacy despite dose escalation. Sequential trials of armodafinil, solriamfetol, mixed amphetamine salts, and methylphenidate were limited by tachycardia, inadequate efficacy or poor tolerability, paranoia, and persistent late-day sleepiness, respectively. Lower-sodium oxybate was subsequently initiated at 3 g once nightly but was reduced to 2.25 g because of significant nausea. With slower, individualized titration to 5.5 g once nightly, the patient reported substantial improvement in daytime sleepiness and functioning. Her ESS score decreased from 18/24 to 4/24, scheduled methylphenidate and caffeine were no longer required, and daytime napping was markedly reduced. This case illustrates the challenges of longitudinal pharmacologic management of IH and highlights the importance of individualized treatment selection, tolerability-guided oxybate titration, and assessment of functional outcomes beyond standardized sleepiness scores.

The improper disposal of pharmaceuticals such as paracetamol and propranolol represent a significant environmental concern due to their high persistence in the environment and low removal efficiency by conventional wastewater treatment processes. In this context, this work aimed to develop and evaluate five adsorbents derived from peanut shells precursor for removal of paracetamol and propranolol in a binary mixture (228 and 279 nm), an application that has not yet been explored for this bioresidue. Among the produced adsorbents, phosphoric-acid-modified activated carbon (CAH3PO4) presented the best performance, achieving removal efficiencies of 99.40% and 99.47% at wavelengths of 228 and 279 nm, respectively. This result can be attributed to its high specific surface area (547 m[2] g [-1]) and the presence of oxygenated and phosphorylated functional groups on the CAH3PO4 surface, formed through thermochemical treatment. The kinetic data were best fitted to pseudo-second order model, indicating the predominance of chemical interactions between adsorbate and adsorbent. In the equilibrium study, the data best fitted the Sips model, suggesting a surface with both homogeneous and heterogeneous adsorption sites. Thermodynamic analysis revealed that the adsorption process is exothermic, indicating spontaneous and energetically favorable interactions. These results highlight the high adsorption potential of CAH3PO4 as an effective and viable alternative for the treatment of pharmaceutical-contaminated effluents.

Objective: To describe the timing, frequency, and accessibility of Instagram posts from pediatric health institutions during the 2025 acetaminophen-autism controversy.Methods: Cross-sectional audit of public Instagram accounts of 62 pediatric health institutions from September 22 to November 15, 2025. The a priori sampling frame comprised the top 50 US children's hospitals for pediatric behavioral health, the top 10 Honor Roll children's hospitals (US News and World Report), 5 national medical societies, and health departments of the 10 states with the largest pediatric populations. Posts were extracted with a web-scraping tool and manually verified. Two reviewers independently coded relevant posts for prespecified content and accessibility features. Readability was assessed with two validated measures.Results: Twelve of 62 institutions (19%) posted relevant content. The American Academy of Pediatrics and the American College of Obstetricians and Gynecologists posted on day 0, while hospital time to first post ranged from 3 to 51 days. No state health department posted. Nonresponding institutions remained active: 1 hospital published 108 unrelated posts. The 26 relevant posts had a mean Flesch-Kincaid Grade Level of 11.4 and SMOG Index of 10.2. Among coded features, 88% included resource links, 73% directed audiences to a health care provider, 46% featured a named clinician, 42% discussed risks and benefits, and none were multilingual.Conclusions: Most sampled institutions published no relevant content during an active health controversy despite remaining active. Readability of relevant posts exceeded recommended targets, and none were multilingual. These gaps in institutional communication infrastructure could be addressed.

Recent studies indicate that injury-induced dedifferentiation generates transient regenerative progenitors (TRPs), which support tissue repair across multiple organs, including the liver. In vivo partial reprogramming using Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc; OSKM) produces intestinal TRPs closely resembling those arising from injury-induced dedifferentiation, but transgenic or viral approaches raise safety concerns because of prolonged expression. Here, we show that transient OSKM induction generates two distinct liver progenitor-like cell (LPLC) populations without injury and with limited activation of injury-associated immune responses. Single-nucleus RNA sequencing shows that one population resembles injury-induced LPLCs observed in acetaminophen-injured mouse and human livers. To develop a temporally controlled regenerative strategy, we establish a liver-targeted lipid nanoparticle system for OSKM mRNA delivery. OSKM mRNA-LNP treatment induces hepatocyte dedifferentiation and Sox9[+] LPLC-like cell formation and is associated with enhanced regeneration after acetaminophen-induced injury. Together, these findings identify transient hepatic reprogramming as a strategy for inducing regenerative plasticity and support liver-targeted OSKM mRNA delivery as a potential approach for acute liver injury.