Int J Pharm [JOURNAL]
Sun
200 papers
Artificial intelligence and CRISPR-based approaches for targeted delivery of bacteriophages.
Pradhan RR, Pati S, Samal SK
Int J Pharm · 2026 Jul · PMID 42402276 · Publisher ↗
The rapid emergence of multidrug-resistant (MDR) bacteria has increased interest in bacteriophage therapy as a promising alternative to conventional antibiotics. Bacteriophages are host-specific bacterial viruses that se...
The rapid emergence of multidrug-resistant (MDR) bacteria has increased interest in bacteriophage therapy as a promising alternative to conventional antibiotics. Bacteriophages are host-specific bacterial viruses that selectively infect and destroy pathogenic bacterial strains. Recent developments in artificial intelligence (AI) and CRISPR-based technologies offer innovative approaches to address challenges such as narrow host range, rapid immune clearance, phage instability, bacterial resistance, and biofilm penetration barriers. By integrating AI-driven structural modeling with CRISPR-mediated genome editing, these methods enable the targeted delivery of bacteriophages. This review focuses on next-generation approaches that combine AI-assisted phage identification, host prediction, and therapeutic optimization with CRISPR-based genome engineering for targeted phage delivery and improved safety. Overall, this review highlights the potential of AI- and CRISPR-assisted phage therapy for the treatment of MDR bacterial infections. This review provides a systematic overview of bacteriophage biology, life cycle, and mechanisms of action, highlighting the influence of phage morphology on therapeutic performance, recent advances, current clinical and preclinical studies, and future perspectives. Although phage therapy shows considerable potential against MDR bacterial infections, several challenges related to delivery, safety, and clinical translation remain. The integration of AI and CRISPR technologies may improve phage selection, targeting specificity, and therapeutic performance. Continued research, clinical validation, and regulatory development will be essential for translating these advances into practical antimicrobial therapies.
A "three-in-one" nose-to-brain delivery strategy: intranasal vancomycin spray achieves simultaneous clearance of pneumococcal colonization, bacteremia, and meningitis.
Wang G, Yi H, Kong X … +10 more , Ou J, Zhou Y, Tang X, Zhang K, Wang W, Zhao Z, Huang Y, Pan X, Wu C, Zhang X
Int J Pharm · 2026 Jul · PMID 42401303 · Publisher ↗
Bacterial meningitis caused by Streptococcus pneumoniae is a lethal central nervous system infection, yet conventional intravenous vancomycin struggles to cross the blood-brain barrier effectively. Interestingly, the nat...
Bacterial meningitis caused by Streptococcus pneumoniae is a lethal central nervous system infection, yet conventional intravenous vancomycin struggles to cross the blood-brain barrier effectively. Interestingly, the natural pathology of this pathogen originates from nasopharyngeal colonization, disseminates into systemic bacteremia, and ultimately breaches the meninges. Inspired by this sequential invasion, we hypothesized that administering vancomycin directly at the exact starting point via a nasal spray could achieve a simultaneous "three-in-one" eradication of all infection stages. To realize this goal and overcome the bottleneck of nasal delivery, we developed a vancomycin nasal spray using hydroxypropyl methylcellulose as a viscosity modifier. By systematically tuning the formulation viscosity, we achieved a synchronous optimization of the macroscopic spray morphology and microscopic droplet behavior. This aerodynamic balance minimized premature droplet impaction at the anterior nasal valve and prevented excessive gravitational settling in the main nasal meatus. Quantitative analysis in a 3D-printed human nasal cast demonstrated that the optimized formulation F4 maximized target site coverage, achieving a total nasal meatus deposition of 2491.7 μg and a peak olfactory deposition fraction of 5.06%. The optimized spray increased cerebrospinal fluid bioavailability by 2.93-fold and drastically reduced peripheral renal exposure by 74.93% compared to intravenous injection. In a pneumococcal infection rat model, the intranasal therapy demonstrated superior multidimensional bactericidal efficacy, clearing 89.81% of the local nasopharyngeal colonies, 97.11% of the systemic bacteremia, and 93.83% of the intracerebral bacterial load. This robust pathogen clearance was accompanied by the prompt resolution of localized neuroinflammation, systemic procalcitonin levels, and circulating leukocyte abnormalities. Ultimately, this aerodynamically engineered formulation provides an anatomically inspired and highly effective intervention paradigm for managing complex central nervous system infections.
10-Hydroxy-2-decenoic acid /matrine deep eutectic solvent encapsulated in hyalurosomes for enhanced transdermal delivery and antioxidant efficacy.
Gao C, Liu F, Yang S … +3 more , Wang Q, Yang C, Liang R
Int J Pharm · 2026 Jul · PMID 42401302 · Publisher ↗
As the primary functional constituent of royal jelly, 10-hydroxy-2-decenoic acid (10-HDA) exhibits potent anti-inflammatory, and antioxidant activities. However, its practical application in cosmetic formulations has bee...
As the primary functional constituent of royal jelly, 10-hydroxy-2-decenoic acid (10-HDA) exhibits potent anti-inflammatory, and antioxidant activities. However, its practical application in cosmetic formulations has been severely limited by poor aqueous and oily solubility. To overcome these drawbacks, a deep eutectic solvent composed of 10-HDA and matrine (designated HM-DES) was first prepared to improve its solubility. Furthermore, HM-DES was encapsulated into sodium hyaluronate-decorated liposomes named hyalurosomes (HA-HM-Lip) to further enhance its transdermal delivery efficiency. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and H nuclear magnetic resonance spectroscopy (H NMR) verified that 10-HDA and matrine formed a stable, amorphous, homogeneous system through intermolecular hydrogen bonding. The optimized HA-HM-Lip formulation was prepared at a 10-HDA-to-matrine molar ratio of 10:8. Zeta potential measurements and transmission electron microscopy (TEM) confirmed the successful coating of sodium hyaluronate onto the liposomal surface. The resulting formulation exhibited excellent stability under various physicochemical stresses, including different temperatures, freeze-thaw cycles, dilution, and high-ionic-strength environments. In vitro transdermal permeation studies revealed that HA-HM-Lip significantly enhanced the deposition of 10-HDA in the stratum corneum, viable epidermis and dermis compared with free 10-HDA, HM-DES, and HM-Lip. Moreover, the HA-HM-Lip system efficiently scavenged DPPH and superoxide anion radicals. Cellular assays revealed that HA-HM-Lip not only reduced intracellular ROS levels in HaCaT cells and markedly suppressed the secretion of pro-inflammatory cytokines (IL-1α, IL-6, and TNF-α), but also promoted HaCaT cell migration and effectively attenuated senescence in HFF-1 cells. In summary, the HA-HM-Lip nanodelivery system established in this study effectively improves the solubility and transdermal permeability of 10-HDA while enhancing its biological activities.
Dual-trigger hyaluronic acid nanoprodrug incorporating a 2-nitrobenzenesulfonyl linker for CD44-targeted and glutathione-responsive drug delivery.
Yukimura T, Seki T, Seki T
Int J Pharm · 2026 Jul · PMID 42401301 · Publisher ↗
Selective intracellular activation of anticancer agents while minimizing toxicity toward non-target tissues remains a major challenge in drug delivery systems (DDSs) and prodrug design. In this study, we designed a hyalu...
Selective intracellular activation of anticancer agents while minimizing toxicity toward non-target tissues remains a major challenge in drug delivery systems (DDSs) and prodrug design. In this study, we designed a hyaluronic acid-based prodrug system, HA-Ns-Dox, that integrates receptor-mediated cellular uptake with intracellular glutathione (GSH)-responsive activation. A doxorubicin (Dox) prodrug modified with a 2-nitrobenzenesulfonyl (Ns) group was synthesized and subsequently conjugated to hyaluronic acid (HA) via click chemistry to generate HA-Ns-Dox with both CD44-targeting capability and GSH-responsive activation properties. HA-Ns-Dox formed stable nanosized assemblies in aqueous solution and exhibited high stability under low-GSH conditions mimicking extracellular environments, whereas concentration-dependent activation of Dox was observed under high-GSH conditions mimicking intracellular reductive environments. In vitro studies demonstrated that HA-Ns-Dox was selectively internalized into the CD44-high human breast cancer cell line MDA-MB-231, accompanied by intracellular prodrug activation and nuclear accumulation of Dox. In contrast, cellular uptake and activation were minimal in the CD44-low cell line MCF-7, and cytotoxicity was significantly suppressed even at high concentrations. Cytotoxicity studies further revealed that HA-Ns-Dox exhibited significant antiproliferative activity in CD44-high cells while substantially reducing toxicity toward non-target cells. Collectively, these findings demonstrate the potential of combining CD44-targeted delivery with GSH-responsive prodrug activation to improve cancer cell selectivity.
Polymeric mixed micellar nanogel enhances dermal delivery and therapeutic efficacy of tofacitinib citrate.
Mahajan A, Sharma G, Sarwal A … +2 more , Singh B, Katare OP
Int J Pharm · 2026 Jul · PMID 42401300 · Publisher ↗
This study aimed to develop and evaluate a polymeric-surfactant stabilized mixed micellar (MM) gel of tofacitinib citrate (TFC) for localized management of rheumatoid arthritis (RA). TFC-MM gel was formulated via a simpl...
This study aimed to develop and evaluate a polymeric-surfactant stabilized mixed micellar (MM) gel of tofacitinib citrate (TFC) for localized management of rheumatoid arthritis (RA). TFC-MM gel was formulated via a simple and scalable cold dispersion self-assembly approach using Lipoid S75, Tween 80, and Poloxamer 407, incorporated into a Carbopol hydrogel matrix. The optimized formulation exhibited nanosized particles (i.e., 67.2 nm), narrow size distribution (PDI ∼ 0.11), and high drug entrapment (i.e., 80.7%). The developed micellar gel showed sustained kind of drug release (i.e., 98.6% in 12 h) compared to the marketed formulation (i.e., 58.2%). Ex vivo permeation and dermatokinetic evaluation using Wistar rat skin showed significantly higher drug deposition and skin retention than those observed with marketed formulations. Confocal imaging further supported improved penetration into deeper skin layers. In vivo pharmacological evaluation in BALB/c mice and Wistar rat models demonstrated superior antinociceptive, anti-inflammatory, and anti-arthritic efficacy vis-à-vis marketed tofacitinib and diclofenac gels. Importantly, mechanistic therapeutic validation was established through a significant reduction in key pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β), along with improvements in biochemical and haematological markers, including CRP, ESR, and leukocyte counts. The formulation also depicted good dermal compatibility and cellular safety. Overall, this study establishes a simple and scalable mixed micellar nanocarrier approach for topical delivery of TFC, demonstrating improved dermal bioavailability, enhanced therapeutic efficacy, and mechanistic anti-inflammatory validation. The findings highlight the potential of MM nanogels as clinically translatable nanocarrier systems for topical RA therapy.
Localized gold nanoparticles-mediated photothermal therapy for head and neck cancer: in vivo proof-of-concept.
Amaral MN, Pereira R, Rodrigues C … +11 more , Nunes D, Fortunato E, Martins R, Santos J, Matias MC, Catarino J, Faísca P, Ferreira HA, Coelho JMP, Gaspar MM, Reis CP
Int J Pharm · 2026 Jul · PMID 42401299 · Publisher ↗
Head and neck cancer (HNC) is the sixth most common cancer worldwide and remains associated with high mortality. Current therapeutic approaches are often aggressive and lead to functional impairment and disfiguration, re...
Head and neck cancer (HNC) is the sixth most common cancer worldwide and remains associated with high mortality. Current therapeutic approaches are often aggressive and lead to functional impairment and disfiguration, reducing quality of life. Minimally invasive and more localized treatment strategies are needed. Gold nanoparticles (AuNPs)-mediated photothermal therapy (PTT) has emerged as a promising approach due to the high photothermal conversion efficiency of AuNPs and their ability to generate localized heat upon near-infrared (NIR) irradiation. This study evaluates the potential of AuNP-mediated PTT for HNC as a proof-of-concept. For this, the physicochemical and optical properties of the AuNPs were characterized. They demonstrated long-term stability, up to one year, and photothermal stability, maintaining performance throughout four irradiation cycles. The efficacy of AuNPs-mediated PTT was assessed in vivo using two murine models differing in tumor location (neck or flank). Following intratumoral administration of AuNPs and repeated laser irradiation cycles, a clear photothermal effect was observed, associated with increased tumor necrosis and a trend toward reduced tumor progression. Biodistribution studies revealed an accumulation of the AuNPs at the tumor. Importantly, safety assessments showed no significant alterations, indicating the absence of systemic toxicity following treatment. Overall, the developed AuNPs demonstrated long-term physicochemical stability, robust photothermal performance, strong intratumoral accumulation and a favorable safety profile. These findings support the potential of AuNPs-mediated PTT as a localized and minimally invasive therapeutic strategy for HNC. Further studies will include the assessment of the long-term therapeutic outcomes to advance this approach towards clinical translation.
Design and evaluation of a pump-free ultrasonic atomization-driven hollow microneedle array for transdermal drug delivery.
Chen X, Niu Y, Zheng C … +4 more , Zhao K, Cai Z, Luo Z, You X
Int J Pharm · 2026 Jul · PMID 42398635 · Publisher ↗
A pump-free hollow microneedle drug delivery system driven by ultrasonic atomization was developed for continuous transdermal administration of liquid drugs. The device integrated an ultrasonic atomization unit, a silico...
A pump-free hollow microneedle drug delivery system driven by ultrasonic atomization was developed for continuous transdermal administration of liquid drugs. The device integrated an ultrasonic atomization unit, a silicone delivery chamber, and a stainless-steel hollow microneedle array. The influences of lumen diameter and chamber configuration on fluid transport performance were systematically evaluated. The results demonstrated that lumen diameter and the positional relationship between the atomizer outlet and needle inlet played critical roles in determining delivery initiation, flow stability, and transport efficiency. Optimized structural parameters enabled more sustained and controllable liquid delivery, while unfavorable geometries led to liquid accumulation and increased flow resistance. In vivo experiments in Sprague-Dawley rats further showed that insulin delivered by the system produced an evident hypoglycemic effect, confirming the feasibility of this platform for transdermal delivery of biomacromolecular therapeutics. These findings indicate that ultrasonic atomization provides an effective driving mechanism for hollow microneedle-mediated drug delivery and highlights its potential application in wearable transdermal therapeutic devices.
Predicting milling performance of pharmaceutical crystals from elastic modulus.
Sen S, Gao T, Xiang T … +3 more , Wang Z, Sun CC, Mara NA
Int J Pharm · 2026 Jul · PMID 42398634 · Publisher ↗
Predicting pharmaceutical milling outcomes from intrinsic material properties remains an unresolved challenge, with current approaches relying on empirically fitted population balance parameters or powder-scale mechanica...
Predicting pharmaceutical milling outcomes from intrinsic material properties remains an unresolved challenge, with current approaches relying on empirically fitted population balance parameters or powder-scale mechanical testing that obscures the role of crystal-level mechanics. This work establishes that a solitary nanoindentation-derived property, the reduced elastic modulus (E), measured on individual API single crystals, quantitatively predicts jet milling particle size reduction across chemically diverse pharmaceutical systems. Ten API single crystals spanning E = 6.3 to 19.0 GPa were characterized by nanoindentation and jet-milled under identical conditions. A Hertzian contact mechanics framework reveals that stiffer crystals generate higher peak contact stresses during particle-particle collisions, activating a greater fraction of pre-existing flaws and producing finer comminution products. Simple linear regression models achieve leave-one-out cross-validated errors below 5% while blind validation on withheld API systems yields relative errors of 1.5-4.2%, confirming genuine predictive capability beyond the training set. Crucially, the model extends to eight external literature systems spanning E = 7.2 to 43.3 GPa, encompassing five different studies with diverse milling equipment, and independently determined modulus values with mean relative errors below 5% for systems within the calibration range. A complementary fracture mechanics analysis demonstrates that coarse particle reduction (Δd%) is governed by the brittleness index (H/K) rather than E, delineating two mechanistically distinct comminution regimes: crack initiation-limited (fines, Er-governed) and crack propagation-limited (coarse tail, H/K-governed). This dual-regime framework provides the first physics-grounded, single-crystal-based predictive tool for pharmaceutical milling, requiring only milligrams of crystalline material.
Lipid digestion- driven drug fate as a key determinant of SNEDDS performance: Mechanistic basis of absorption and in vitro- in vivo disconnect.
Chhetri P
Int J Pharm · 2026 Jul · PMID 42392240 · Publisher ↗
Self-nanoemulsifying drug delivery systems (SNEDDS) represent a major class of lipid-based nanomedicines that are primarily utilised for the enhancement of oral delivery of poorly water-soluble drugs. However, their clin...
Self-nanoemulsifying drug delivery systems (SNEDDS) represent a major class of lipid-based nanomedicines that are primarily utilised for the enhancement of oral delivery of poorly water-soluble drugs. However, their clinical translation remains inconsistent due to a sustained divergence between in vitro performance and in vivo bioavailability. Although substantial literature exists, a unified mechanistic framework linking these outcomes is still seen to be lacking. This review critically examines the underlying causes of the translational gap, emphasising identifying key limitations in current evaluation strategies and the misalignment between standard formulation metrics and processes relevant to absorption. It reconceptualises SNEDDS as a dynamic, digestion-mediated system in which drug fate is dictated by time-dependent interactions between lipid transformation, drug redistribution, and physiological variability. Particular focus is given to the underexplored determinants, including supersaturation persistence, post-digestion drug redistribution, and constraints in lymphatic transport. A predictive, mechanism-based design framework is proposed linking drug properties, lipid behaviour, and physiological constraints together. Future directions highlight the potential of adaptive in vitro systems, multi-scale modelling, and artificial intelligence-driven optimisation to ensure more reliable, context-aware SNEDDS development and also improved clinical translation.
Redox-responsive nanomedicine beyond glutathione: harnessing reactive oxygen species and emerging endogenous triggers for precision drug delivery.
Swain K, Maity A, Pattnaik S
Int J Pharm · 2026 Jul · PMID 42391851 · Publisher ↗
Redox-responsive nanomedicine has emerged as a promising approach for site-selective drug delivery by leveraging pathological redox imbalances. Nevertheless, the majority of systems predominantly depend on glutathione (G...
Redox-responsive nanomedicine has emerged as a promising approach for site-selective drug delivery by leveraging pathological redox imbalances. Nevertheless, the majority of systems predominantly depend on glutathione (GSH) as a universal trigger, an assumption that frequently fails to account for the complexity and heterogeneity of endogenous redox biology across various diseases. This review critically evaluates redox-responsive nanomedicine beyond GSH, emphasizing emerging endogenous redox triggers such as reactive oxygen species (ROS), thioredoxin systems, NADPH-dependent pathways, hypoxia, and disease-specific oxidative signatures. We discuss advancements in redox-responsive chemistries, logic-gated and multi-trigger nanocarrier designs, and disease-adapted delivery strategies across oncology, inflammatory, metabolic, cardiovascular, and neurodegenerative disorders. Importantly, we analyze translational bottlenecks responsible for bench-to-bedside attrition and propose design principles to enhance biological relevance, safety, and clinical success. By integrating redox biology with nanocarrier engineering, this review outlines a roadmap toward precision redox-responsive drug delivery.
Preventing tablet defects through vacuum-assisted deaeration of a powder bed.
Thiele K, Randall E, Klinzing GR … +1 more , Howard M
Int J Pharm · 2026 Jul · PMID 42385991 · Publisher ↗
Lamination is a common defect observed during pharmaceutical tablet compression and can be attributed to air entrapment (lamination type 1) within the powder bed. In this study, a novel vacuum-inducing chamber was implem...
Lamination is a common defect observed during pharmaceutical tablet compression and can be attributed to air entrapment (lamination type 1) within the powder bed. In this study, a novel vacuum-inducing chamber was implemented to remove air from the powder bed prior to compaction, thereby enabling, for the first time, a systematic investigation of lamination type 1 while decoupling air entrapment from other contributing factors. Microcrystalline cellulose (MCC) was compacted on a Huxley Bertram compaction simulator equipped with a vacuum chamber under systematically varied compressive stresses, strain rates, and ambient air pressures. Consistent with established findings, reducing compressive stress and strain rate decreased the frequency and severity of lamination defects, supporting the role of process parameters in defect formation. However, when the ambient air pressure surrounding the die and punches was sufficiently reduced, lamination defects were reduced or eliminated across the range of process parameters studied. These findings provide direct experimental evidence that modulating ambient air pressure can influence lamination defects due to air entrapment in MCC tablets. Furthermore, numerical simulations of air pressure evolution upon compression showed that altering air pressure can have a greater impact on air pressure reduction than processing conditions. The novel vacuum chamber approach offers an experimental platform for studying defect formation and suggests that control of ambient pressure during compaction may represent an effective strategy for mitigating lamination type 1 during pharmaceutical tablet manufacturing.
Approaches for enhancing bioavailability of macromolecular drugs.
Xiao Z, Wang S, Han J … +7 more , Zou Z, Xing B, Wang J, Feng J, Jin Y, Cheng M, Tu L
Int J Pharm · 2026 Jun · PMID 42379329 · Publisher ↗
Compared with small-molecule drugs, macromolecular drugs offer advantages such as high safety, strong specificity, and low immunogenicity. Although macromolecular drugs suffer from inherently low bioavailability and face...
Compared with small-molecule drugs, macromolecular drugs offer advantages such as high safety, strong specificity, and low immunogenicity. Although macromolecular drugs suffer from inherently low bioavailability and face multiple physiological barriers, a systematic review that comprehensively summarizes the strategies to overcome these challenges is still lacking. Therefore, developing effective strategies to enhance the bioavailability of macromolecular drugs represents a highly promising research direction. Numerous studies have shown that macromolecular drugs prepared through biotechnology can be used in combination with various biological carriers to activate the immune system by inducing the production of immune cells and immune factors, thereby achieving disease prevention and treatment. This article reviews the multiple absorption barriers encountered by macromolecular drugs, such as peptides and proteins, in different delivery systems, as well as the strategies to improve their bioavailability and the technical approaches to overcome the related delivery challenges, aiming to provide theoretical references and a foundation for the design of novel macromolecular drug delivery systems.
Characteristics of asymmetric microcrystalline solidification pellets and a better prediction for bioequiavailability based on solubility-permeability theory.
Wang Y, Xiao P, Wei N … +7 more , Zhou Y, Yin T, Zhang Y, He H, Gou J, Wang Y, Tang X
Int J Pharm · 2026 Jun · PMID 42379328 · Publisher ↗
Controlled release of poorly soluble drugs and the impact of solubilization on in vivo oral absorption remain pivotal concerns in pharmaceutical research. This study developed asymmetric microcrystalline solidified pelle...
Controlled release of poorly soluble drugs and the impact of solubilization on in vivo oral absorption remain pivotal concerns in pharmaceutical research. This study developed asymmetric microcrystalline solidified pellets (AMSPs) with excellent stability, capable of precisely regulating the in vitro release of poorly soluble drugs. Based on the solubility-permeability theory, an effective method was proposed to predict the in vivo absorption behavior of these pellets. Using fenofibrate (FBT) as the model drug, a microcrystalline suspension was prepared via wet grinding to enhance the dissolution rate. The resulting suspension was then solidified onto the surface of blank pellets using an asymmetric layered loading strategy, yielding AMSPs that enhance the stability of the microcrystalline suspension while enabling controlled drug release. The surface structure of the steady-state crystals within the suspension was characterized as a dynamically equilibrated semi-solid phase using colorimetry and H NMR spectroscopy. By varying drug loading density and mass ratios across different drug-loaded compartments, the release behaviors of different AMSP configurations were systematically analyzed to achieve precise in vitro controlled release. Further more, sodium taurocholate (STC) was selected as a representative compound to investigate the relationship between solubility and permeability, leading to the development of a predictive model for evaluating the effects of food and surfactants on drug absorption. Validated by single-pass jejunal perfusion and bioavailability studies, the model demonstrated strong potential to reduce the cost and experimental burden of in vitro and in vivo investigations while improving the prediction of oral bioavailability. In summary, this research provides valuable insights into the controlled release and oral absorption enhancement of poorly soluble drugs, contributing to their development in pharmaceutical sciences.
A CFPD-FSI analysis of the impact of nasal hairs on airflow patterns, nasal resistance, and particle filtration in a realistic human nasal airway.
Fatahi H, Dastan A, Aghaei A … +2 more , Sadrizadeh S, Abouali O
Int J Pharm · 2026 Jun · PMID 42372839 · Publisher ↗
Human nasal hair has a potential capability to maintain respiratory health, yet its functional significance is frequently underappreciated due to cosmetic preferences. Despite its physiological relevance, the mechanical...
Human nasal hair has a potential capability to maintain respiratory health, yet its functional significance is frequently underappreciated due to cosmetic preferences. Despite its physiological relevance, the mechanical influence of nasal hair on airflow dynamics and particle deposition remains inadequately understood. This study used computational fluid-particle dynamics and fluid-structure interaction (CFPD-FSI) simulations to analyze three distinct nasal hair configurations in a realistic human nasal airway model under steady laminar flow conditions (5 and 10 L/min per cavity). The Discrete Phase Model (DPM) was utilized to predict the transport and deposition of microparticles in the nasal cavity with and without nasal hairs. The one-way coupled CFD-FSI study showed that the investigated airflow rates lead to a negligible deformation in hairs (in the worst-case scenario, 7.8 μm at the hair tip), which implies that the rigid hair assumption can be confidently used for the nasal hairs in the laminar regime. The findings also revealed that the presence of nasal hair can increase nasal resistance by approximately 20-80% while enhancing micro-particle filtration efficiency by 12-38%, depending on the morphological configuration. Furthermore, the results demonstrated that nasal hair alters local airflow patterns in the anterior part of the upper airways, specifically by enhancing swirling flows in the nasal valve region, thereby increasing deposition fraction in this zone. These findings provide quantitative evidence of the physiological role of nasal hair as a protective filtration mechanism and its simultaneous unfavorable impact on nasal resistance and intranasal drug delivery.
Transient hydrate formation during disintegration of film-coated pharmaceutical tablets.
Ma M, Zeng X, Powell D … +4 more , Nassar M, Teckoe J, Markl D, Zeitler JA
Int J Pharm · 2026 Jun · PMID 42372838 · Publisher ↗
The transformation of anhydrous tablet excipients into their hydrated forms occurs simultaneously with film coating dissolution, yet the kinetics of this process remain poorly understood. Water molecules diffuse through...
The transformation of anhydrous tablet excipients into their hydrated forms occurs simultaneously with film coating dissolution, yet the kinetics of this process remain poorly understood. Water molecules diffuse through the immediate release film coating and form hydrogen bonds with the anhydrous components within the tablet core, creating a thermodynamic driving force that competes with the hydration of the coating polymer. This study investigates the influence of film coating properties, including the base polymer (polyvinyl alcohol versus hydroxypropyl methylcellulose), coating thickness, and coating density, alongside tablet core properties such as porosity and excipient type. Using polymer-coated tablets containing anhydrous lactose or magnesium sulphate, we demonstrate that terahertz pulsed imaging (TPI) captures this diffusion process non-destructively. We characterise the anhydrous-to-hydrate transformation based on subtle refractive index changes at the interface. We identify distinct hydration mechanisms for channel hydrates versus ion-coordinated hydrates, providing further evidence that the core formulation actively regulates water ingress prior to coating failure. These findings offer critical insights for the predictive modelling of film-coated tablet disintegration and dissolution.
Erratum to "In vitro - In vivo correlation modeling of an oxcarbezapine extended-release formulation using numerical deconvolution" [Int. J. Pharm. 699 (2026) 126952].
Kakhi M, Chen H, Chittenden J
Int J Pharm · 2026 Jun · PMID 42372647 · Publisher ↗
Abstract loading — click title to view on PubMed.
Use of a hydrophilic excipient to modulate the release of dapivirine, copper ions and zinc ions from a matrix-type vaginal ring.
Shen X, Zhao X, Boyd P … +4 more , Dallal Bashi YH, McCoy CF, Murtadha RZ, Malcolm RK
Int J Pharm · 2026 Jun · PMID 42364791 · Publisher ↗
Two major challenges for developers of drug-releasing vaginal rings are (i) the formulation and release of hydrophilic water-soluble actives, which generally require novel ring designs, very high drug loadings, and/or in...
Two major challenges for developers of drug-releasing vaginal rings are (i) the formulation and release of hydrophilic water-soluble actives, which generally require novel ring designs, very high drug loadings, and/or inclusion of substances to modify the release mechanism and enhance release, and (ii) the incorporation and release of multiple actives, particularly when the actives have very different solubility/permeability characteristics. In this study, as part of ongoing efforts to develop inexpensive and easily-manufactured multipurpose vaginal rings for HIV prevention, non-hormonal contraception, and prevention of bacterial and viral sexually transmitted infections, we describe formulation development and testing of matrix-type silicone elastomer rings containing combinations of three actives-dapivirine (D), copper sulfate anhydrous (C), and zinc sulfate monohydrate (Z)-and the hydrophilic excipient hydroxypropyl methylcellulose (H). Inclusion of H significantly impacted in vitro release and the properties of the vaginal rings, including mechanical performance, ring dimensions, and swelling. Preliminary testing of a lead candidate triple-active DCZH ring prototype showed good stability.
Reprogramming chronic wounds: the emerging role of microbiome-targeted therapies in diabetic foot ulcers.
Kamal R, Chauhan A, Bhargava SK … +4 more , Dhiman S, Singh TG, Kumar D, Awasthi A
Int J Pharm · 2026 Jun · PMID 42364790 · Publisher ↗
Diabetic foot ulcers (DFUs) represent one of the most severe complications of diabetes mellitus, frequently leading to chronic infection, delayed wound healing, and lower-limb amputations. Despite advances in wound care,...
Diabetic foot ulcers (DFUs) represent one of the most severe complications of diabetes mellitus, frequently leading to chronic infection, delayed wound healing, and lower-limb amputations. Despite advances in wound care, current therapeutic strategies largely rely on broad-spectrum antibiotics and mechanical interventions, which often fail to address the complex biological environment of non-healing wounds. Emerging evidence indicates that DFUs are strongly associated with alterations in the wound microbiome, including microbial dysbiosis, polymicrobial biofilm formation, and persistent inflammatory responses. These factors collectively contribute to impaired tissue regeneration and resistance to conventional therapies. Consequently, microbiome-targeted therapeutic strategies are gaining increasing attention as a promising approach for DFU management. Novel interventions such as bacteriophage therapy, probiotic and postbiotic-based wound dressings, and CRISPR-mediated genome editing provide precise tools for disrupting pathogenic biofilms, attenuating microbial virulence, and overcoming antimicrobial resistance while preserving beneficial microbial communities. In parallel, advances in rapid microbiome diagnostics, smart wound dressings, nanotechnology-based drug delivery systems, and data-driven personalized treatment platforms are enabling more adaptive and targeted wound management. By shifting the perspective from treating DFUs as simple infections to understanding them as complex microbial ecosystems, these emerging strategies offer new opportunities to enhance healing outcomes.
Fabrication of Spanlastics as a potential transdermal delivery of lornoxicam for efficient management of osteoarthritis and side effect mitigation: Formula optimization, in vitro characterization, ex vivo, and in vivo assessments.
El-Dahmy RM, El-Mallahy NM, Teaima MH … +2 more , Awny MM, El-Mancy SS
Int J Pharm · 2026 Jun · PMID 42362001 · Publisher ↗
Lornoxicam (LRX) is a strong non-steroidal anti-inflammatory drug used for managing osteoarthritis (OA). LRX has low oral bioavailability because of its low water solubility and extensive first-pass effect. This study ai...
Lornoxicam (LRX) is a strong non-steroidal anti-inflammatory drug used for managing osteoarthritis (OA). LRX has low oral bioavailability because of its low water solubility and extensive first-pass effect. This study aimed to develop spanlastics (SPs) for sustained transdermal delivery of LRX to enhance its solubility, permeability, anti-osteoarthritic efficacy, and minimize its oral side effects. LRX-SPs were prepared using the ethanol injection method based on a D-optimal design. The optimized SP formula (F4) consisted of LRX (10 mg), Kolliphor RH40 (200 mg), Span 60 (500 mg), and oleic acid (200 mg). It showed the least particle size (137.8 ± 6.93 nm), polydispersity index (0.23 ± 0.02), and the highest entrapment efficiency% (88.7 ± 4.01%), zeta potential (-34.6 ± 3.58 mV). F4 enhanced LRX release and ex vivo permeation by 1.69- and 2.04-fold compared to LRX suspension, respectively. Then F4 was converted to gel by adding 1% Carbopol, which boosted LRX release and ex vivo permeation by 1.52- and 1.78-fold, respectively, compared with free LRX gel. In vivo evaluation of anti-inflammatory activity of SP gel by MIA-induced OA in rats has verified significant inhibition of knee joint edema, oxidative stress/inflammatory cascades, as compared with free LRX gel and market tablet. Besides, the SP gel has reverted MIA-induced alteration of joint degradation/regeneration and apoptotic markers. These findings were mirrored in animals' motor performance tests and histopathological investigations, confirming the SP gel's efficacy in reducing OA deterioration without halting gastroprotective prostaglandin E2 levels. Therefore, it could be considered a promising approach for transdermal delivery of LRX for managing OA.
Cyclodextrin inclusion as a pharmaceutical reaction field: kinetic, pathway and structural control beyond equilibrium.
Hiroshige R, Goto S
Int J Pharm · 2026 Jun · PMID 42362000 · Publisher ↗
Cyclodextrins (CDs) are widely used pharmaceutical excipients typically evaluated within equilibrium thermodynamic frameworks. However, many degradation processes, including radical-driven oxidation, photochemical reacti...
Cyclodextrins (CDs) are widely used pharmaceutical excipients typically evaluated within equilibrium thermodynamic frameworks. However, many degradation processes, including radical-driven oxidation, photochemical reactions, and tautomerism-coupled instability, proceed under nonequilibrium conditions that cannot be fully explained by binding constants alone. This review presents CDs as molecular-scale reaction fields that modulate kinetic accessibility, pathway competition, and structural population distributions. Using three representative systems, we illustrate distinct modes of control: kinetic suppression of radical encounters in edaravone oxidation, pathway reorganization in ketoprofen photochemistry revealed by singular value decomposition (SVD), and structural equilibrium bias in avobenzone. By integrating kinetic analysis, time-resolved spectroscopy, and multivariate approaches, we present evidence that CDs can regulate reaction behavior beyond equilibrium complexation. This framework provides a basis for understanding formulation-dependent stability and offers design principles for CD-enabled stabilization strategies under nonequilibrium conditions.
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