Harendra S. Parekh

Intranasal phase-transforming thermoresponsive gels provide extended nasal residence, supporting a range of nose-to-brain therapeutic and diagnostic applications, including imaging. However, quantitative and real-time release characterisation for multi-modal probes for imaging remains limited. Here, we developed a poloxamer-based sol-gel and established a hybrid PET/MRI framework to quantify the release of PET tracers and an activatable MnO2 nanoflower into simulated nasal fluid. The formulations transformed from solution-to-gel at ~28–29 °C with an elastic moduli of 8.2−9.5 kPa attained at typical nasal cavity temperature (34 °C), while maintaining a nasal-compatible pH. PET imaging with an extended time window demonstrated diffusion-dominated release with clear size dependence: ionic [64Cu]Cu2+ reached 30.0 ± 3.0% cumulative release at ~42 h, whereas [64Cu]Cu-Sar-OP only released 15.6 ± 3.1% under the same simulated conditions. PEGylated MnO2 nanoflowers exhibited negligible apparent release in simulated nasal fluid without reductant due to the absence of redox-triggered MnO2 dissolution to soluble Mn2+ and electrolyte-induced nanoparticle aggregation trapping, which restricts diffusion out of the gel; but with GSH-supplementation, quantitative T1/T2 mapping enabled relaxivity-calibrated tracking of Mn2+ generation, reaching 13.9 ± 0.7% release (T1-based) at ~24 h. Kinetic modelling (Higuchi and Korsmeyer−Peppas) suggested Fickian diffusion for all probes, with minor anomalous diffusion characteristics for the redox-responsive PEGylated MnO2 system. Overall, our integrated PET/MRI platform provides a quantitative framework for selecting imaging agents, acquisition windows and sol-gel design parameters for developing intranasal PET/MR agents spanning molecular and nanoscale payloads.

The all-wine industry is projected to generate over US$528 billion in sales globally by 2025, and like many mass-producing industries, it too generates significant waste and by-products, much of which ends up in landfill. Among the various agricultural and industrial by-products, residues from winemaking stand out for their exceptionally rich and diverse bioactive compound content, primarily originating from grape skins, seeds and stems, all of which are rich in polyphenols, organic acids and tannins. These compounds have remarkable antioxidant, antimicrobial and anti-inflammatory properties and can therefore be diverted to agricultural, food preservation, cosmetic and pharmaceutical industries. The mechanism of action of the array of bioactive compounds includes disruption of microbial cell membranes, reduction of oxidative stress, and modulation of inflammatory responses. The current literature is limited to highlights of the scale of waste generated, and the application of its bioactive agents, however, it is notably absent of critical appraisal and discussion in sustainable avenues for development and value-added products, which are comprehensively elaborated herein.

Purpose: Antimicrobial resistance (AMR) associated with sexually transmitted infections (STIs) is a serious public health concern that has resulted in the failure of available treatment options and necessitated the use of innovative drug delivery platforms. Herein, linezolid (LzD)-infused sol-gels have been prepared for intravaginal drug delivery in drug-resistant STIs. Methods: Sol-gel formulations were prepared using poloxamer 407 (P407), poloxamer 188 (P188), hydroxypropyl methyl cellulose E4M (HPMC E4M), and methyl paraben (MP) in citrate buffer (CB). The rheomechanical properties, in vitro drug release, and stability of optimised sol-gels were investigated. Further, ex vivo bovine vaginal tissue permeation and tissue deposition, HeLa-cell-based toxicity evaluation, and antimicrobial screening against methicillin-sensitive and methicillin- and oxacillin-resistant Staphylococcus aureus (S. aureus) were carried out with the lead sol-gel. Results: The sol-gels demonstrated a gelation temperature (T _sol-gel ) of 26–28 °C, an osmolality < 1200 mOsm/kg, and a pH of ~ 4.0, while displaying a sustained in vitro drug release (54–59 % release at 72 h). LzD and rheological stability was maintained during the study period. The lead sol-gel (F10) displayed low tissue permeability (~4.5%) and favourable tissue deposition (202.55 ± 9.50 µg/g) at 6 h, HeLa cell compatibility, and notable antimicrobial activity against both methicillin- and oxacillin-resistant strains of Staphylococcus aureus (S. aureus). Conclusion: These studies demonstrate that the sol-gel platform has immense potential for managing drug-resistant STIs, with a low risk of AMR due to localised drug delivery, minimal systemic exposure, dose reduction ( c.f. oral delivery), and increased patient compliance.

Heat‐shock protein 70 (HSP70) and nanotechnology have emerged as promising avenues in glioblastoma multiforme (GBM) therapy, addressing the critical challenges posed by its aggressive nature and therapeutic resistance. HSP70’s dual role in cellular stress response and tumour survival emphasises its potential as both a biomarker and therapeutic target. This review explores the innovative integration of HSP70 with nanotechnology, emphasising advancements in imaging, drug delivery and combination therapies. Nanoparticles, including SPIONs, liposomes, gold nanoparticles and metal–organic frameworks, demonstrate enhanced targeting and therapeutic efficacy through HSP70 modulation. Functionalized nanocarriers exploit HSP70’s tumour‐specific overexpression to improve drug delivery, minimise off‐target effects and overcome the blood–brain barrier. Emerging strategies such as chemophototherapy, immunotherapy and photothermal therapy leverage HSP70’s interactions within the tumour microenvironment, enabling synergistic treatment modalities. The review also highlights translational challenges, including heterogeneity of GBM, regulatory hurdles and variability in the enhanced permeability and retention (EPR) effect. Integrating computational modelling, personalised approaches and adaptive trial designs is crucial for clinical translation. By bridging nanotechnology and molecular biology, HSP70‐targeted strategies hold transformative potential to redefine GBM diagnosis and treatment, offering hope for improved survival and quality of life. Trial Registration: ClinicalTrials.gov identifier: NCT00054041 and NCT04628806

Bioactive glasses (BGs) are widely used in orthopedic and dental applications for their ability to stimulate endogenous bone formation and regeneration. BG applications more recently broadened to include soft tissue conditions, based on their ability to stimulate angiogenesis, soft tissue regeneration, and wound healing. Sol-gel synthesis has helped facilitate this expansion, allowing formulators to tailor the morphological characteristics of the BG matrix. The effectiveness of BGs in skin wound healing is viewed as a gateway for their use as both a therapeutic and drug delivery platform in other soft tissue applications, notably gastrointestinal (GI) applications, which form the focus of this review. Recent changes in international guidelines for GI conditions shifted clinical objectives from symptom management to mucosal wound healing. The additional scrutiny of proton pump inhibitor (PPI) safety, increasing burden of disease, and financial costs associated with gastroesophageal reflux disease (GERD), peptic ulcer disease (PUD), and inflammatory bowel disease (IBD) open new clinical possibilities for BG. This narrative literature review intersects materials engineering, formulation science, and clinical practice, setting it apart from prior literature. Broadly, current evidence for BG applications in GI conditions is sparse and under-developed, which this review directly addresses. It explores and synthesizes evidence that supports the potential use of sol-gel-derived BG for the efficacious treatment of soft tissue applications, with specific reference to GI conditions. An overview with comparative analysis of current BG synthesis techniques and associated challenges is presented, and influences of composition, biologically active ions, and morphological characteristics in soft tissue applications are explored. To contextualize this, sol-gel-derived BGs are proposed as a dual, tailorable therapeutic and drug delivery platform for upper and lower GI conditions. Future directions for this largely untapped area of translational research are also proposed, based on extant literature.

Ultrasound has long been identified as a promising, non-invasive modality for improving ocular drug delivery across a range of indications. Yet, with 20 years of learnings behind us, clinical translation remains limited. To help address this, and in accordance with PRISMA guidelines, the various mechanisms of ultrasound-mediated ocular drug delivery have been appraised, ranging from first principles to emergent applications spanning both ex vivo and in vivo models. The heterogeneity of study methods precluded meta-analysis, however an extensive characterisation of the included studies allowed for semi-quantitative and qualitative assessments.