Int J Pharm [JOURNAL]
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200 papers
Development and validation of an in vitro permeation test method for rectal mesalamine suppositories.
Xie L, Kelchen M, Ghosh P … +3 more , Niu M, Raney SG, Shen J
Int J Pharm · 2026 Jun · PMID 42155617 · Full text
For locally-acting rectal drug products, an assessment of bioequivalence has traditionally necessitated an in vivo comparative clinical endpoint bioequivalence study. By contrast, for locally-acting dermal drug products,...
For locally-acting rectal drug products, an assessment of bioequivalence has traditionally necessitated an in vivo comparative clinical endpoint bioequivalence study. By contrast, for locally-acting dermal drug products, an in vitro permeation test (IVPT) using excised skin has become a useful tool to evaluate and compare topical bioavailability as a component of bioequivalence approaches for products applied to the skin. However, whether an IVPT study using excised mucosal tissue could be used in a similar manner to efficiently evaluate the rate and extent of local bioavailability for transmucosal drug products (e.g., rectal drug products) was unknown. To explore this, the present research thoroughly investigated the key considerations such as mucosal tissue handling procedures, study duration, individual animal donor tissue variation as well as method validation strategies for IVPT studies with locally-acting rectal drug products, using mesalamine rectal suppositories as model transmucosal drug products. A reproducible and discriminatory IVPT method using excised porcine rectal tissues mounted in a vertical diffusion cell (VDC) was successfully developed and IVPT method validation strategies were investigated. The established IVPT method was capable of detecting differences in drug permeation resulting from differences in strength, dose duration, and dosage form (suppository vs. solution) under the conditions evaluated. A comparative IVPT study was conducted to characterize the rate and extent of drug permeation behavior for the marketed reference listed drug (RLD) product and laboratory-made (LM) mesalamine rectal suppositories using excised porcine rectal tissues from multiple donors. The results of our research demonstrated the feasibility of utilizing IVPT studies with mucosal tissues to evaluate the in vitro performance of locally-acting rectal semisolid drug products. Data from such studies are in vitro surrogates that are expected to enhance our understanding of local drug bioavailability from these drug products and may contribute to an overall assessment of bioequivalence in the future.
Improving the palatability of Platycodonic Radix for pediatric use: Integrating LC-MS-based bitter component profiling with an HP-β-Cyclodextrin/xylitol taste-masking strategy.
Zhou Z, Zhang S, Fang C … +9 more , Cheng H, Yasheng M, Yuan J, Cai W, Fang Z, Wu F, Wang Y, Xue Z, Zhang X
Int J Pharm · 2026 Jun · PMID 42155616 · Publisher ↗
Platycodonic Radix (PR) is a key herb in traditional Chinese prescriptions for pediatric respiratory disorders. However, its intense bitterness and persistent throat astringency reduce treatment compliance. This study es...
Platycodonic Radix (PR) is a key herb in traditional Chinese prescriptions for pediatric respiratory disorders. However, its intense bitterness and persistent throat astringency reduce treatment compliance. This study established a mechanism-informed taste-masking strategy integrating chemical profiling, sensory evaluation, and formulation optimization. PR sensory characteristics were first quantified using human panels and an electronic tongue. Subsequently, PR water extracts were characterized by non-targeted profiling based on liquid chromatography-mass spectrometry (LC-MS). Putative bitter constituents were further screened using BitterX-assisted TAS2R molecular docking. The optimized formulation was then validated in two representative pediatric formulas containing the classical "PR-Glycyrrhiza uralensis Fisch." herb pair. LC-MS tentatively identified 308 compounds in PR decoctions, mainly carbohydrates and glycosides. Docking results indicated that platycodigenin, polygalacic acid, lactone-type platycodins, luteolin, and lignans show high affinity for human bitter taste receptors TAS2R14, TAS2R44, and TAS2R47, confirming a multi-component basis for PR bitterness. Among the excipients tested, 2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) and xylitol were most effective. Mechanistically, HP-β-CD primarily suppressed residual bitterness and astringency, whereas xylitol improved initial mouthfeel. An optimized combination of 6.5 % HP-β-CD plus 10 % xylitol (w/w relative to PR) successfully transformed PR decoctions from "difficult to accept" to "sweet with no lingering bitterness", a shift corroborated by electronic tongue DFA plots. This strategy improved palatability in two representative pediatric formulas without altering the herbal composition. These findings demonstrate that 6.5 % HP-β-CD plus 10 % xylitol effectively alleviates both initial bitterness and throat irritation, offering a practical, non-destructive solution to enhance pediatric medication adherence in traditional phytotherapy.
Development and in vivo evaluation of novel bioresponsive nanocubosomal in-situ gelling system for ophthalmic delivery of Amphotericin B.
Sanjana SP, Shivakumar HN, Shinde R … +2 more , Kumar R, Hariprasad MG
Int J Pharm · 2026 Jun · PMID 42150646 · Publisher ↗
Amphotericin B (AmB), the drug of choice for fungal keratitis, displays poor aqueous solubility, physiological instability, and pH-dependent aggregation causing ocular irritation. This study aimed to develop novel recons...
Amphotericin B (AmB), the drug of choice for fungal keratitis, displays poor aqueous solubility, physiological instability, and pH-dependent aggregation causing ocular irritation. This study aimed to develop novel reconstitutable bioresponsive Nanocubosomal in situ gelling system (NCG) of AmB to address the above-mentioned limitations. Initially, 13 batches of Nanocubosomal Dispersion (NCD) were formulated using Quality by Design-driven central composite design with glyceryl monooleate as lipid, poloxamer 407 as surfactant, and dimethyl sulfoxide as solvent, employing high-shear homogenization and ultrasonication. The optimised NCD exhibited nanoscale size (158.9 ± 2.6 nm), low polydispersity (0.162 ± 0.007), high entrapment efficiency (91.2 ± 1.1%), and colloidal stability (zeta potential -32.8 ± 1.3 mV). Due to low pH-solubility (0.2 ± 0.03 µg/mL) at pH 7.4 and moderate lipophilicity (log P: 0.46 ± 0.01), AmB would get preferentially localised in lipid domain. The optimised batch of NCD was finally lyophilised with Carbopol 934 (0.3%w/v) and mannitol (5%w/v) before gamma sterilisation to obtain NCG. NCG demonstrated bioresponsive behaviour, maintaining low pre-instillation viscosity (12 ± 0.9 mPa.s) while instantly transforming into resilient pseudoplastic gel (22,230 ± 310 mPa.s) at ocular pH that is likely to prolong ocular retention. The in-vitro drug release from NCG at 24 h was found to be significantly lower compared to marketed lyophilised Amfocare® (p < 0.0001), indicating sustained release behaviour. NCG displayed significantly enhanced (p < 0.01) antifungal activity against Candida albicans compared to Amfocare®. Draize testing in rabbits ruled out possibility of ocular irritation, demonstrating improved tolerability of NCG. Overall, NCG, by its ability to maintain AmB in monomeric form, represents a promising, stable, effective, irritation-free in situ gelling lipid-based platform for treatment of fungal keratitis.
Apparent interfacial bonding strength in hybrid overprinted bilayer tablets: influence of 3D printing parameters on mechanical integrity.
Xu H, Ebrahimi F, Gong K … +3 more , Liu H, Fuenmayor E, Major I
Int J Pharm · 2026 Jun · PMID 42150645 · Publisher ↗
Hybrid manufacturing by overprinting, in which 3D-printed layers are deposited directly onto injection-moulded substrates, offers a promising route to personalised oral solid dosage forms. A key challenge is achieving su...
Hybrid manufacturing by overprinting, in which 3D-printed layers are deposited directly onto injection-moulded substrates, offers a promising route to personalised oral solid dosage forms. A key challenge is achieving sufficient adhesion between the moulded substrate and the printed layer to minimise delamination during handling and downstream processing. This study investigated the influence of fused filament fabrication parameters, including printing speed, layer height, nozzle temperature, infill density, and infill pattern, on the apparent interfacial bonding strength of overprinted bilayer tablets composed of polycaprolactone and PVP-VA. Adhesion was evaluated by tensile pull-off testing, supported by fracture-surface analysis using digital microscopy and internal defect mapping by computed tomography. Lower printing speed (10 mm/s), reduced layer height (0.15 mm), elevated nozzle temperature (185 °C), and specific infill strategies, particularly high initial density and a wiggle pattern, significantly increased pull-off strength. In contrast, higher porosity and incomplete filament fusion promoted fracture within the printed region and reduced apparent bond strength. CT analysis showed that reduced defect fraction correlated with higher pull-off strength and altered failure mode. These findings establish a clear process-structure-property relationship and support optimisation of overprinting conditions for mechanically robust hybrid bilayer tablets.
Formulation of poorly water-soluble drugs in lipid nanocarriers: a suitable approach for taste masking or bitter-taste enhancing?
Scholten J, Pein-Hackelbusch M, Sokolowsky M … +2 more , Park J, Steiner D
Int J Pharm · 2026 Jun · PMID 42150644 · Publisher ↗
The taste of a drug formulation, especially of orodispersible and liquid dosage forms, is of crucial importance due to its direct contact with the human taste buds. In order to achieve high patient acceptance with these...
The taste of a drug formulation, especially of orodispersible and liquid dosage forms, is of crucial importance due to its direct contact with the human taste buds. In order to achieve high patient acceptance with these formulations, drugs with an unpleasant, predominantly bitter taste have to be masked. One strategy for masking taste particularly suitable for lipophilic drugs is to dissolve the drug molecules in lipid carrier systems, such as nanoemulsions. Although this strategy has often proven effective as a formulation strategy for improving bioavailability and masking an unpleasant taste, our study indicates that embedding the three poorly water-soluble model drugs fenofibrate, simvastatin, and naproxen in nanoemulsions led to newly created or increased bitterness compared to the non-formulated drug powders. We proved this using both an analytical taste sensor system, specifically an electronic tongue (e-tongue), and a sensory study with a human taste panel. Hereby, complete agreement between the e-tongue measurements and the sensory study was found despite the non-ionic character of fenofibrate and simvastatin. We hypothesize that the changed bitter taste impressions were due to the location of the drug molecules at the oil/water interfaces, which resulted in an increased bitter taste intensity and prolonged duration of the bitter taste. In summary, the study shows that incorporating drugs into lipid nanocarriers tended to worsen the taste rather than mask it.
Combined antimicrobial and pro-healing effects of cathelicidins in a polysaccharide-based hydrogel scaffold: treatment of carbapenemase-resistant Pseudomonas aeruginosa wound infections in a porcine model.
Pavelka A, Lipový B, Janda L … +14 more , Brtníková J, Knoz M, Holoubek J, Váňa V, Jeklová E, Straková P, Makovický P, Šefranko M, Kleknerová DP, Volný F, Chamradová I, Vojtová L, Růžička F, Vacek L
Int J Pharm · 2026 Jun · PMID 42150643 · Publisher ↗
Given the global rise in antibiotic resistance, this study focuses on developing an alternative treatment for deep skin and soft tissue infections (SSTIs) caused by a carbapenem-resistant Pseudomonas aeruginosa. An injec...
Given the global rise in antibiotic resistance, this study focuses on developing an alternative treatment for deep skin and soft tissue infections (SSTIs) caused by a carbapenem-resistant Pseudomonas aeruginosa. An injectable hydrogel composed of polyvinyl alcohol and chitosan was developed as a stable carrier for the porcine cathelicidins PR-39 and Protegrin-1. In vitro tests demonstrated that the addition of 8 mM EDTA fully restores the activity of antibacterial peptides in fetal bovine serum and eliminates the influence of divalent cations. In a porcine model, the application of this hydrogel resulted in a significant reduction in bacterial load after only two doses, with levels dropping below 10 CFU/g of tissue. In addition to eliminating the infection, the treated group showed early granulation tissue formation, reduced necrosis and inflammation, and the development of a continuous epidermis, all of which were completely absent in the untreated group. The research confirms that the combination of cathelicidins and EDTA in a hydrogel carrier represents a highly effective approach for treating complicated bacterial infections.
Evaluation of media for cell differentiation in a nasal mucosa model based on the epithelial cell line Cl-pNaEC for preclinical drug testing.
Klintz LPI, Reichl S
Int J Pharm · 2026 Jun · PMID 42144168 · Publisher ↗
The reliable transferability of preclinical testing is crucial for reducing cost and time in the implementation of new active substances and formulations. Therefore, in vitro models can replace animal testing, if the mod...
The reliable transferability of preclinical testing is crucial for reducing cost and time in the implementation of new active substances and formulations. Therefore, in vitro models can replace animal testing, if the model is reliable, fully characterized and able to replicate the physiological characteristics accurately. Recently, the porcine nasal epithelial cell line CI-pNaEC was introduced as a candidate for a suitable in vitro model of nasal mucosa, as it shows mucociliary differentiation and appropriate permeation properties. In this study, CI-pNaEC was exposed to seven commercially available culture media (huNASA, PneumaCult, BEGM, BEpiCM, LHC-9, AECGM and mAir) at air-liquid interface and tissue-specific differentiation of the resulting nasal mucosa models was evaluated in terms of histology, mucus quality and quantity, barrier properties and ciliation. Mucus expression was analyzed quantitatively and the mucus diffusion barrier was studied using fluorescence recovery after photobleaching. Epithelial barrier formation was tested by determination of transepithelial electrical resistance and permeation studies using marker molecules. Differentiation of ciliated cells was studied microscopically and using immunostaining method. For huNASA and PneumaCult, features that closely mirror the in vivo characteristics of nasal epithelium such as abundant mucus expression and ciliation were expressed. In contrast, BEpiCM and mAir cultures showed diminished mucus production and reduced ciliation, while nasal mucosa constructs cultivated in BEGM, LHC-9, and AECGM exhibited only minimal mucus expression, no ciliation, and markedly higher barrier resistance. The study demonstrates a clear impact of the culture media examined on the expression of tissue-specific characteristics and thus on the suitability of the constructs as alternatives to animal testing, with huNASA and PneumaCult appearing to be the more suitable media.
In vitro - In vivo correlation modeling of an oxcarbezapine extended-release formulation using numerical deconvolution.
Kakhi M, Chen H, Chittenden J
Int J Pharm · 2026 Jun · PMID 42144167 · Publisher ↗
An in vitro - in vivo correlation (IVIVC) for an oxcarbazepine (OXC) extended-release formulation, originally submitted as part of a regulatory submission and found to be inadequate, was re-evaluated using two-stage nume...
An in vitro - in vivo correlation (IVIVC) for an oxcarbazepine (OXC) extended-release formulation, originally submitted as part of a regulatory submission and found to be inadequate, was re-evaluated using two-stage numerical deconvolution and found to be predictively robust by meeting internal and external validation criteria. This result was achieved by enhancing the unit impulse response (UIR) characterization and using nonlinear IVIVC mapping functions. The predictive IVIVC was then applied to determine dissolution acceptance criteria, which showed good agreement with the currently approved criteria for the lower bound of dissolution. Furthermore, IVIVCs that linked in vitro drug release of OXC to the in vivo response of the active metabolite showed higher overall accuracy compared to IVIVCs that linked OXC's in vitro drug release to its own in vivo response. This finding was attributed to the stronger rank-order correlation between the active metabolite's pharmacokinetics and the in vitro data.
Discrete element analysis of the effect of particle cohesion on die filling behaviour of pharmaceutical powders in a rotary tablet press.
Alizadeh Behjani M, De Souter L, Zheng C … +3 more , Nitert BJ, De Beer T, Wu CY
Int J Pharm · 2026 Jun · PMID 42144166 · Publisher ↗
This study investigates the effect of particle cohesion on die filling behaviour in a rotary tablet press using a combined Discrete Element Method (DEM) and experimental approach. This DEm model can support decision maki...
This study investigates the effect of particle cohesion on die filling behaviour in a rotary tablet press using a combined Discrete Element Method (DEM) and experimental approach. This DEm model can support decision making for tablet formulations during drug product development when availability of active substance materials is limited and pilot scale trials are not feasible. Microcrystalline Cellulose (MCC) spheres were characterised experimentally and used as the model powder. A validation study is conducted where tablet weight and its variability, obtained from DEM simulations, and corresponding experiments are compared. In addition, Residence Time Distribution (RTD), with both pulse and step change inputs, are obtained numerically and experimentally to further validate the DEM models. A satisfactory agreement between the DEM and experimental results was obtained. Systematic DEM simulations are then performed to explore the influence of powder cohesion on die filling behaviour. The results revealed that increasing powder cohesion reduces tablet weight (uniformity) considerably under constant fill depth. Additionally, more cohesive powders have a propensity to remain in the feed frame for a longer time under similar process conditions. It is also shown that optimal tablet weight with minimal variability could be obtained at intermediate turret speeds, whereas high turret speeds (90 rpm) are associated with lower tablet weight uniformity. Additionally, at low turret speeds, increasing paddle speed to an intermediate level improve process efficiency, notably through increases in mean tablet weight and tablet weight uniformity when fill depth is kept constant. These simulations elucidate the critical factors affecting tablet manufacturing, allowing for the optimisation of process parameters to maximise weight uniformity and performance while minimising experimental burden.
Mesoporous polydopamine-based biomimetic nanodelivery systems: recent advances in precision therapy.
Tao C, Lu S, Wang K … +6 more , Chen W, Li R, Mao S, Zhou M, Shang J, Luo H
Int J Pharm · 2026 Jun · PMID 42142678 · Publisher ↗
Mesoporous Polydopamine (MPDA) integrates a mesoporous architecture with dopamine chemistry, offering a high specific surface area, tunable pore size, abundant surface reactive sites, together with good biocompatibility...
Mesoporous Polydopamine (MPDA) integrates a mesoporous architecture with dopamine chemistry, offering a high specific surface area, tunable pore size, abundant surface reactive sites, together with good biocompatibility and excellent photothermal conversion efficiency, which collectively confer distinct advantages for drug delivery. However, unmodified MPDA is readily cleared by the immune system in vivo and lacks active targeting capability, limiting its therapeutic potential. Introducing biomimetic modifications, such as biological membrane coatings, can endow MPDA with prolonged circulation, immune evasion, and targeting capability, thereby markedly improving its stability and delivery efficiency in complex in vivo environments. This review systematically summarizes the structural design, biological functions, and research progress of MPDA-mediated biomimetic nanodelivery systems, with emphasis on their applications in tumors, inflammation, wound healing, antifibrotic therapy, and antiatherosclerotic therapy, encompassing multimodal strategies including chemotherapy, radiotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, and immunotherapy. With continued advances in biomimetic membrane engineering, biomanufacturing, and imaging technologies, MPDA-based biomimetic nanodelivery systems are expected to provide new avenues for precision medicine.
Hyaluronic acid-modified nanoparticles with Fe/ HO supply and GSH depletion capabilities to improve breast cancer therapy via induction of ferroptosis.
He C, Zhao Y, Mo M … +5 more , Su Y, Qi Z, Chen XD, Zhou W, Yu F
Int J Pharm · 2026 Jun · PMID 42142677 · Publisher ↗
Ferroptosis is an iron-dependent programmed cell death modality characterized by the massive accumulation of lipid peroxides (LPO). However, the efficiency of ferroptosis is commonly limited by insufficient supply of iro...
Ferroptosis is an iron-dependent programmed cell death modality characterized by the massive accumulation of lipid peroxides (LPO). However, the efficiency of ferroptosis is commonly limited by insufficient supply of iron ions and endogenous hydrogen peroxide (HO) in the tumor cells. To overcome these drawbacks, MIL-100 NPs were synthesized via a microwave-assisted method to encapsulate β-lapachone (Lap), followed with the hyaluronic acid (HA) surface modification (designated as LMH NPs). LMH NPs exhibited GSH-responsive degradation in the tumor cells to release Lap and Fe. The released of Lap could generate HO via catalysis by tumor-overexpressed quinone oxidoreductase 1 (NQO1), leading to increased intracellular HO levels. The abundant production of HO could supply substrates for Fe-mediated Fenton reactions to produce toxic hydroxyl radicals (·OH), thereby promoting LPO accumulation and enhancing ferroptosis. Meanwhile, Fe released from LMH NPs was reduced to Fe through GSH consumption, which could diminish glutathione peroxidase 4 (GPX4) activity. In vitro and in vivo experiments confirmed that LMH NPs possessed effective targeted uptake and exhibited optimal tumor inhibition without significant toxic side effects. Overall, the integrated strategy presents a novel ferroptosis-based clinical approach for enhanced breast cancer therapy.
Effect of vascular disrupting therapy by lipid nanoparticles on the tumor microenvironment.
Nagaoki T, Endo R, Ueda T … +3 more , Sato Y, Yamada Y, Nakamura T
Int J Pharm · 2026 Jun · PMID 42142676 · Publisher ↗
Tumor vascular disruption represents an attractive yet underexplored therapeutic strategy in cancer nanomedicine. We previously developed a lipid nanoparticle (LNP)-based vascular disrupting strategy combining cyclic RGD...
Tumor vascular disruption represents an attractive yet underexplored therapeutic strategy in cancer nanomedicine. We previously developed a lipid nanoparticle (LNP)-based vascular disrupting strategy combining cyclic RGD peptide-modified LNPs delivering siRNA against Fas ligand (cRGD-LNP/siFasL) to tumor endothelial cells with STING agonist-loaded LNPs (STING-LNPs), which cooperatively induce tumor vascular collapse through type I interferon-dependent mechanisms. However, the determinants of therapeutic responsiveness remain poorly defined. Here, we elucidated tumor microenvironmental factors governing heterogeneous therapeutic responses across syngeneic tumor models. While the combination therapy elicited robust vascular disruption and antitumor efficacy in CT26 and Renca tumors in BALB/c mice, its efficacy was markedly attenuated in B16-F10 and LLC tumors in C57BL/6 mice, independent of host genetic background. In refractory LLC tumors, the gene silencing efficiency in tumor endothelial cells was substantially lower (∼40% vs. ∼79% in responsive tumors), resulting in limited vascular disruption. Transcriptomic profiling suggested that the enhanced extracellular matrix remodeling and augmented innate immune activation within the tumor microenvironment may increase the susceptibility of tumor vasculature to the combination therapy. Flow cytometric analyses demonstrated significantly higher expression of IFNAR1, mediating type I interferon signaling, in responsive tumors. Collectively, this study suggests the tumor-intrinsic immune and stromal features that dictate responsiveness to LNP-mediated vascular disrupting therapy and provides a mechanistic framework for optimizing next-generation vascular-targeted nanomedicines.
Self-enhanced copper-doped Prussian blue nanoplatform for amplifying enzyme-like activity and photothermal effects.
Chen Y, Hu B, Liu L … +5 more , Wang X, Qi Z, Zhang J, Sun Y, Yuan Y
Int J Pharm · 2026 Jun · PMID 42142675 · Publisher ↗
Chemodynamic therapy (CDT) has emerged as a promising anticancer strategy, yet its therapeutic efficacy is significantly hampered by the elevated glutathione (GSH) levels in the tumor microenvironment (TME) and the limit...
Chemodynamic therapy (CDT) has emerged as a promising anticancer strategy, yet its therapeutic efficacy is significantly hampered by the elevated glutathione (GSH) levels in the tumor microenvironment (TME) and the limited catalytic efficiency of conventional Fenton reactions. To address these challenges, we developed copper-doped Prussian blue nanoparticles (CPB NPs) for encapsulating curcumin (CUR) and further modified their surface with the active targeting molecule hyaluronic acid (HA), forming CPB@CUR-HA NPs. Notably, this nanoformulation significantly enhances solubility and bioavailability of CUR. In the constructed system, Prussian blue (PB) serves a dual function as an effective photothermal agent: it not only induces tumor cell ablation through photothermal effects but also amplifies CDT efficacy via localized temperature elevation. The incorporated copper ions play crucial roles in depleting excessive GSH and catalyzing Fenton-like reactions, thereby boosting the peroxidase-like activity of PB. Furthermore, copper doping synergistically improves the photothermal conversion efficiency of PB. The mutually reinforcing interplay between CDT and photothermal therapy (PTT), combined with the natural anticancer agent CUR, enables a powerful trimodal therapeutic approach integrating chemotherapy, CDT, and PTT, ultimately achieving remarkable tumor growth inhibition.
Chondroitin sulfate-functionalized GSH-responsive lipid-nanoparticle inhibits melanoma metastasis through suppressing STAT3 activation.
Yao Y, Zhang M, Xu S … +4 more , Wu G, Meng X, Li J, Yu H
Int J Pharm · 2026 Jun · PMID 42142674 · Publisher ↗
Tumor metastasis results in high mortality rate in patients with advanced melanoma. The hyperphosphorylation of signal transducer and activator oftranscription3 (STAT3) is closely associated with the proliferation and me...
Tumor metastasis results in high mortality rate in patients with advanced melanoma. The hyperphosphorylation of signal transducer and activator oftranscription3 (STAT3) is closely associated with the proliferation and metastasis of melanoma. Here, we proposed a lipid-nanoparticle (CSD@DNLP) derived from the chondroitin sulfate (CS)-conjugated deoxycholic acid (DOCA) polymer (CS-ss-DOCA, CSD) for the co-delivery of doxorubicin (DOX) and STAT3 inhibitor nifuroxazide (NIF) in metastatic melanoma treatment. The superior affinity between CS and overexpressed CD44 receptors in B16F10 cells resulted in 3.3-fold enhancement of cellular uptake compared to free DOX. CSD@DNLP maintained structural stability in physiological conditions, while achieving 75.15% cumulative release within 48 h under a tumor-mimic concentration of glutathione (GSH, 20 mM). Synergistic effects were observed through NIF-mediated STAT3 phosphorylation blockade and DOX-induced DNA damage, resulting in 3.2-fold enhancement in apoptotic cells versus free drugs. In lung metastasis mice, CSD@DNLP suppressed metastatic nodule formation (36% of free DOX + NIF) via dual downregulation of matrix metalloproteinases-2 (MMP-2) and metalloproteinases-2 (MMP-9). This CS-functionalized GSH-responsive lipid-nanoparticle demonstrates a promising strategy in metastatic melanoma.
Optimizing dry powder delivery during invasive mechanical ventilation via circuit absolute humidity control.
Tsai RB, Huijgen T, Ke WR
Int J Pharm · 2026 Jun · PMID 42142673 · Publisher ↗
Dry powder inhalers (DPIs) are rarely used during invasive mechanical ventilation (IMV) because intubated patients cannot generate sufficient inspiratory effort, and ventilator circuits require heated humidification that...
Dry powder inhalers (DPIs) are rarely used during invasive mechanical ventilation (IMV) because intubated patients cannot generate sufficient inspiratory effort, and ventilator circuits require heated humidification that may impair powder dispersion. This study evaluated whether a ventilator-actuated, enclosed DPI chamber combined with a rapidly adjustable absolute humidifier can enable efficient DPI delivery under clinically relevant IMV conditions. An in vitro IMV model was operated in volume-controlled ventilation (15 breaths/min; I:E 1:2; square waveform; peak flow 50 L/min). An enclosed delivery chamber housing a capsule DPI (Breezhaler®; indacaterol 150 µg with lactose carriers) was inserted in-line during expiration and actuated for 15 breaths. Circuit humidity was controlled using an Absolute Humidifier Prototype at 0, 11, 22, 33, and 44 mg/L absolute humidity (AH; 0-100% RH at 37 °C) and compared with a pass-over humidifier (MR850; ∼40 mg/L AH). Tidal volume (VT) was 400-800 mL, and endotracheal tube (ETT) size was 7.5 or 9.5 mm internal diameter (ID). Inhaled dose was defined as the drug mass collected on the inspiratory filter distal to the ETT, and the aerodynamic particle size distribution (APSD) of inhaled dose was measured using an NGI. Inhaled dose showed a bidirectional dependence on humidity. At VT 600 mL with a 7.5-mm ETT, the inhaled dose peaked at 39.9 ± 0.9% of the labeled dose at 22 mg/L AH, decreased slightly at 33 mg/L AH (32.0 ± 1.6%), and dropped markedly near saturation at 44 mg/L AH (10.0 ± 2.2%); MR850 produced a similarly low inhaled dose (10.8 ± 1.2%). Increasing ETT ID from 7.5 to 9.5 mm reduced ETT deposition across 0-33 mg/L AH (e.g., 10.3 ± 0.7% to 5.8 ± 0.7% at 0 mg/L, p < 0.05) and increased inhaled dose at low humidity (e.g., 28.4 ± 2.0% to 36.3 ± 2.5% at 0 mg/L, p < 0.05). VT had little influence at 0-22 mg/L AH, but at high humidity, the inhaled dose increased (44 mg/L AH, 9.5-mm ETT: 13.3 ± 1.9 µg at VT 400 vs 37.0 ± 4.2 µg at VT 800, p < 0.05). APSD was largely stable across humidity and VT. Mass median aerodynamic diameter remained 2.76 ± 0.15 to 3.07 ± 0.03 µm, and geometric standard deviation showed no significant humidity effect. Fine particle dose (<5 µm) peaked at 26.1 ± 4.6 µg at 11 mg/L AH and decreased to 8.0 ± 2.7 µg at 44 mg/L AH (p < 0.05). A ventilator-actuated, enclosed chamber, combined with real-time humidity control, enabled efficient DPI delivery during IMV. Delivery was optimized at intermediate humidity (22 mg/L AH) and reduced at both humidity extremes. These data indicated controllable humidification is critical for translating DPI therapy into mechanically ventilated care.
Corrigendum to "Dual-responsive drug delivery systems prepared by blend electrospinning" [Int. J. Pharm. 543(1-2) (2018) 1-7].
Li H, Sang Q, Wu J … +5 more , Williams GR, Wang H, Niu S, Wu J, Zhu LM
Int J Pharm · 2026 Jun · PMID 42142434 · Publisher ↗
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Corrigendum to "Thermosensitive nanofibers loaded with ciprofloxacin as antibacterial wound dressing material" [Int. J. Pharm. 517(1-2) (2017) 135-147].
Li H, Williams GR, Wu J … +4 more , Lv Y, Sun X, Wu H, Zhu LM
Int J Pharm · 2026 Jun · PMID 42140762 · Publisher ↗
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Preclinical development of a 3D-printed hollow microneedle platform for intradermal delivery of antioxidant-loaded nanocarriers.
Basto R, Junqueira LA, Tabriz AG … +5 more , Douroumis D, Pereira-Leite C, Rosado C, Lima SAC, Reis S
Int J Pharm · 2026 Jun · PMID 42140402 · Publisher ↗
The poor penetration of topical antioxidants underscores the need for advanced intradermal delivery platforms that overcome stratum corneum limitations while protecting labile compounds. Despite their efficacy, in-clinic...
The poor penetration of topical antioxidants underscores the need for advanced intradermal delivery platforms that overcome stratum corneum limitations while protecting labile compounds. Despite their efficacy, in-clinic treatments (microneedling, laser, injections) require frequent administration and entail high costs. Hollow microneedles (HMNs) provide a minimally invasive, precise, and versatile platform for intradermal drug delivery. Combined with nanotherapy approaches, they can protect labile compounds and enable localized release profiles. Here, we report the preclinical development of two designs of a 3D-printed HMN platform for intradermal delivery of resveratrol-loaded PLGA nanoparticles (RSV-NPs), as a proof-of-concept for antioxidant treatments. The HMNs fabricated by DLP 3D printing show precise geometry, favorable margin of safety, and enhanced RSV retention in the skin. An important advantage of this technology is the easy tunability of microneedle size, a critical parameter for depth-specific insertion and delivery control. Histological analysis confirms HMN (1 mm) reach the dermis, while HMN (1.5 mm) penetrate the dermis-hypodermis interface, enabling distinct delivery depths. RSV-NPs display optimal size, stability, high encapsulation efficiency, RSV photoprotection, sustained release, and controlled antioxidant activity with good biocompatibility. In vivo studies in human volunteers confirm the skin compatibility of the nanocarrier alone.
Nanomaterial-mediated lactate metabolism regulation for enhanced cancer immunotherapy.
Yan J, Zhao Z, Sun F … +1 more , Li B
Int J Pharm · 2026 Jun · PMID 42140401 · Publisher ↗
Metabolic reprogramming makes tumor cells prefer aerobic glycolysis as the main energy source, resulting in abnormal accumulation of lactate in the tumor microenvironment (TME). Lactate plays a crucial role in regulating...
Metabolic reprogramming makes tumor cells prefer aerobic glycolysis as the main energy source, resulting in abnormal accumulation of lactate in the tumor microenvironment (TME). Lactate plays a crucial role in regulating cellular metabolism, tumor metastasis and invasion, and immune cell function, and has become an important obstacle in cancer treatment. Therefore, the regulation of lactate in the TME has become a promising target for cancer treatment. Nanomaterials provides a powerful tool for precisely regulating lactate metabolism. Through targeted delivery, controlled release, and multifunctional integration, nanoplatforms can effectively deplete lactate or inhibit its production, thereby reversing the acidic and immunosuppressive state of the TME, and transforming "cold" tumors into immunologically sensitive "hot" tumors. Furthermore, nanomaterials can synergistically interact with metabolic regulation through the catalytic and photothermal properties, inducing immunogenic cell death and activating antitumor immune responses. In view of this, this review summarizes the strategies for regulating lactate mediated by nanomaterials and their effects on antitumor immunity, and discusses their combined potential with immunotherapy. It also analyzes the challenges and future prospects for translating nanomaterials targeting lactate into clinical applications. Nanomaterials are emerging as a bridge connecting tumor metabolic reprogramming and immunotherapy, paving the way for a new paradigm in cancer treatment.
Stability of nanosuspensions in drug delivery: mechanisms, characterization strategies, and advanced stabilization approaches.
Ma Y, Wang L, Wang Y
Int J Pharm · 2026 Jun · PMID 42140400 · Publisher ↗
Poorly soluble drug delivery is a long-standing core challenge in the pharmaceutical field. With a drug loading capacity close to 100% and no requirement for carrier materials, nanosuspensions offer an ideal solution for...
Poorly soluble drug delivery is a long-standing core challenge in the pharmaceutical field. With a drug loading capacity close to 100% and no requirement for carrier materials, nanosuspensions offer an ideal solution for delivering poorly soluble drugs. By reducing the drugs particle size to 100-500 nm, the nanosuspensions exhibited satisfied surface area and dissolution kinetics improvement. However, nanocrystals possess inherent thermodynamic and kinetic instability, driven by their high surface energy. The main stability problem is Ostwald ripening, aggregation, sedimentation, polymorphic transition, and chemical degradation. This instability has become a critical bottleneck limiting their industrialization and clinical translation. Compared with traditional trial-and-error methods, we systematically summarizes the core role of nanosuspensions stability in formulation development. It deeply analyzes the manifestations and intrinsic mechanisms of instability, and comprehensively outlines both traditional strategies and innovative technologies for improving stability. We focuses on the application progress of artificial intelligence, specifically in stability prediction, stabilizer screening, and process optimization. Novel stabilizer types, their action mechanisms, and research status are discussed in detail. At last, we reviewed current research challenges and prospects future development directions under the integration of multiple disciplines. This review delivers systematic theoretical support and practical guidance for the field. We hope these insights can help drive large-scale adoption of nanosuspension technology for poorly soluble drug delivery.
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