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4 papers

Covalent grafting of hyaluronic acid on drug nanocrystals for mucosal delivery.

Fuster MG et al. · Jul 1, 2026

Nanocrystals (NCs) represent an advanced drug delivery platform due to their nearly 100% drug loading capacity, enhanced solubility, and improved tissue penetration. The surface-rich structure of NCs enables chemical modifications, with covalent grafting emerging as a superior strategy to impart stability and introduce targeted functional groups. In this study, we explore the development of curcumin nanocrystals (CUR-NCs) covalently grafted with hyaluronic acid (HA). To enhance mucosal targeting and permeation, HA was chemically grafted to chitosan (CS) on the NCs' surface via EDC/NHS-mediated chemistry. This surface conjugation was confirmed through FTIR and 1 H-NMR analyses, validating the successful formation of HA-CS-CUR-NCs. The resulting nanoparticles exhibited an average particle size of 110 nm, remaining within the ideal range for mucosal delivery. Importantly, cytotoxicity assays on THP1 monocytes and NIH/3T3 fibroblasts revealed that the HA-CS-CUR-NCs possessed suitable biocompatibility properties. Ex vivo mucosal deposition studies using neonatal porcine tissue demonstrated significantly improved mucopenetration with HA-functionalized NCs, achieving 37.3 ± 2.6% drug deposition after 24 hours, compared to only 1.81 ± 1% for non-functionalized CUR-NCs. These findings position HA-CS-CUR-NCs as a promising platform for advanced mucosal drug delivery, combining nanoscale precision with bioresponsive surface chemistry to enhance therapeutic outcomes.

Pharmacology, Toxicology and Pharmaceutics

Combined electrospun fibre-microneedle patches for enhanced transmucosal delivery of benzodiazepines and proteins.

Berry C et al. · Jul 1, 2026

The oral mucosa is highly vascularised, which permits rapid drug uptake into the systemic circulation, avoiding first-pass metabolism for chemicals that penetrate the epithelial permeability barrier. Electrospun mucoadhesive patches have been developed for controlled drug delivery and although contact times and drug distribution are improved, transmucosal drug permeation is still limited to small lipophilic molecules. Incorporation of solid microneedles with an electrospun patch to physically disrupt the epithelial barrier whilst simultaneously delivering a payload, can overcome these issues whilst addressing the drug-loading limitations often experienced with microneedles. Here, we developed a mucoadhesive patch and microneedle composite for delivery of the benzodiazepine, midazolam hydrochloride, required for rapid, systemic delivery to treat status epilepticus and antigen-binding fragments (f(ab)), proteins too large to cross the epithelial permeability barrier. Solid polylactic acid microneedles were manufactured through reverse micromoulding, optimised for buccal permeation and imaged using optical coherence tomography. Electrospun mucoadhesive patches, loaded with midazolam hydrochloride or f(ab), were combined with the microneedles and permeation through tissue-engineered buccal mucosa quantified by high-performance liquid chromatography or immunoassay and imaged by fluorescence confocal microscopy. Microneedle-mediated patch delivery enhanced patch retention time, drug delivery rates and overall permeation when compared to patch-only controls, facilitating rapid delivery of time-sensitive midazolam within minutes, and a 15-fold increase in f(ab) permeation over 2 h, importantly delivering it through the epithelium into the underlying lamina propria. This study demonstrates that microneedle-mediated mucoadhesive patches can enhance transmucosal drug delivery for poorly-permeable drugs and holds significant potential when rapid, systemic drug delivery is required.

Pharmacology, Toxicology and Pharmaceutics

Accuracy of Patient-Reported Exposure to New Psychoactive Substances and Other Illicit Drugs in Australian Emergency Departments: Findings From the Emerging Drugs Network of Australia.

Nijmeijer MJ et al. · Jul 1, 2026

Introduction New psychoactive substances (NPS) present a unique challenge in clinical, public health and drug-policy contexts. Continued diversity, unknown potency and often unintentional exposure can limit the accuracy of self-reported data. This study examined the accuracy of patient-reported NPS and illicit drug exposure in Australian emergency departments (ED). Methods Patient-reported drug exposure, clinical and toxicology data were extracted from the Emerging Drugs Network of Australia Clinical Registry between 1 July 2021 and 30 June 2024 for patients presenting with severe and/or unusual illicit drug toxicity in the ED. Blood samples were analysed using mass spectrometry. Agreement between reported and confirmed exposure was assessed using Cohen's kappa, sensitivity, specificity and likelihood ratios. Logistic regression analysis identified factors associated with discrepancies between reported and confirmed exposures. Results There were 2044 presentations: 64.6% male, median age 33 years (Q1-Q3, 26-41). Complete agreement between patient-reported and confirmed drug exposures was 14.3% (n = 293). Agreement between reported and confirmed NPS exposure was poor (κ = 0.38). 1522 (74.5%) had more drugs detected than reported. Older age (OR 1.03 [CI 1.02, 1.04]) was associated with higher odds of discrepancy. Attendance from a licensed venue (OR 0.44 [CI 0.28, 0.70]) and Glasgow Coma Scale of 13-15 (OR 0.44 [CI 0.33, 0.57]) were associated with lower odds. Discussion and conclusions Poor agreement between patient-reported and analytically confirmed drug exposure highlights the need for continued partnerships between EDs, clinical toxicologists, and forensic laboratories to identify substances involved in acute intoxications and support public health and harm reduction responses.

Pharmacology, Toxicology and Pharmaceutics

Accelerating Subcutaneous Drug Development: A Mechanistic Absorption Model for the Open Systems Pharmacology Framework.

Pellowe M et al. · Jul 1, 2026

This study describes the implementation of a mechanistic subcutaneous (SC) injection model for the Open Systems Pharmacology platform. As the SC route of administration is gaining increased popularity, there is a growing need for tools to predict, analyze, and understand the SC absorption process and the mechanisms involved. The interplay between molecular, formulation, administration, and physiological properties influences both the rate and extent of drug appearance in circulation. The primary objective of this study was to provide a structural modeling basis for mechanistic simulations of drug absorption after SC administration, considering fundamental molecular properties and systemic disposition characteristics. A key aspect of the model design was the intention to support generalizability and translational application across drug characteristics and species, providing a consistent structure for both small molecules and biologics. The SC model was implemented leveraging the structure and parameterization of PK-Sim to allow unified integration to the whole-body physiologically based pharmacokinetic model. An input-response analysis and a set of case examples were conducted to visualize model responsiveness and illustrate potential application in drug development. The generic framework may also serve as the backbone for further implementations to describe complex injection and formulation dependencies. Collectively, this framework establishes a mechanistic foundation for the simulation of SC drug absorption of both small molecules and biologics, providing a basis for further development and informed evaluation across preclinical and clinical stages within the Open Systems Pharmacology platform.

Pharmacology, Toxicology and Pharmaceutics