Int J Pharm [JOURNAL]
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200 papers
Intranasal administration of a DNA vaccine complexed with sugar-functionalized chitosan induces protective immunity against SARS-CoV-2 in mice.
Colaço M, Panão-Costa J, Lebre F … +2 more , Alfaro-Moreno E, Borges O
Int J Pharm · 2026 Jul · PMID 42229833 · Publisher ↗
The emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its devastating global impact emphasize the urgent need for effective, non-invasive vaccines. While current mRNA and adenoviral vaccines h...
The emergence of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and its devastating global impact emphasize the urgent need for effective, non-invasive vaccines. While current mRNA and adenoviral vaccines have mitigated severe disease, they face challenges in preventing mucosal transmission and addressing the emergence of new viral variants. This study investigated an intranasal DNA vaccine encoding the SARS-CoV-2 spike protein, delivered using four sugar-functionalized chitosan-based formulations designed to target antigen-presenting cells (APCs). Two formulations were based on lactobionic acid-modified chitosan, including one combined with laminarin (7.5:1 and LAM25), while the remaining formulations incorporated mannose and/or gluconic acid-modified chitosan (C6M9 and AG40), to modulate APC targeting and intracellular DNA release behavior. All four formulations were first evaluated in human monocyte-derived APCs to assess uptake and immunostimulatory activity, including maturation and pro-inflammatory responses. LAM25 and AG40 emerged as the most active formulations and were selected for further immunological assessment. These were subsequently tested in an autologous mixed lymphocyte reaction, where both promoted strong T cell activation with a Th1-skewed profile. Finally, LAM25 and AG40 were assessed in in vivo intranasal immunization studies in mice, inducing robust systemic and mucosal antibody responses, as well as antigen-specific cellular immunity in spleen and lung tissues and a balanced Th1/Th2/Th17 cytokine profile. These findings underscore the immunostimulatory potential of functionalized chitosan as a mucosal adjuvant, highlighting its promise for enhancing vaccine efficacy and guiding the development of next-generation SARS-CoV-2 vaccines.
Engineered EV-mediated delivery of an anti-amyloid peptide provides neuroprotection in an in vitro Alzheimer's disease model.
Singh VB, Gupta S, Sella RN
Int J Pharm · 2026 Jul · PMID 42229832 · Publisher ↗
Alzheimer's disease is driven in part by amyloid-β (Aβ) aggregation, oxidative stress, and progressive neuronal dysfunction. Despite various attempts, therapeutic translation remains limited by inefficient delivery of bi...
Alzheimer's disease is driven in part by amyloid-β (Aβ) aggregation, oxidative stress, and progressive neuronal dysfunction. Despite various attempts, therapeutic translation remains limited by inefficient delivery of bioactive molecules to neuronal cells. This study presents a surface-engineered extracellular vesicle (EV) platform designed for targeted peptide delivery, assessing its neuroprotective efficacy in an in vitro model of Alzheimer's disease. EVs were obtained from NIH/3T3 cells expressing Lamp2b-RVG and were surface-modified with the β-sheet breaker peptide H102 through CP05-CD63 affinity binding. ATR-FTIR, SERS Raman spectroscopy, high-resolution transmission electron microscopy, nanoparticle tracking analysis, zeta potential measurements, and EV marker profiling demonstrated successful peptide conjugation and vesicle integrity. Aggregated Aβ25-35 was utilized to assess neuronal toxicity in NGF-differentiated PC-12 cells. Peptide-modified EV demonstrated effective, time-dependent cellular uptake and significantly improved cell viability while decreasing membrane damage and intracellular reactive oxygen species levels in comparison to Aβ-treated controls. Treatment with Peptide-modified EV normalized the expression of key genes associated with Alzheimer's, such as APP, Bax, Sirt1, and Stat1, suggesting a coordinated modulation of amyloidogenic, apoptotic, oxidative, and inflammatory pathways. The results indicate that surface-engineered EVs facilitate efficient neuronal delivery of therapeutic peptides and offer multi-level cytoprotection against Aβ-induced neurotoxicity. This study emphasizes the capability of peptide-decorated EV as a multifunctional nanocarrier system for the treatment of Alzheimer's disease.
cR10-modified liposomes for efficient topical delivery of lenvatinib to the posterior segment: Enhanced suppression of choroidal neovascularization.
Xie Y, Zhang X, Yin Q … +4 more , Chen R, Chen F, Huang Y, Shentu X
Int J Pharm · 2026 Jul · PMID 42225176 · Publisher ↗
Choroidal neovascularization (CNV) is a key pathological process underlying multiple retinal diseases and remains difficult to treat due to physiological barriers that limit drug delivery to the posterior segment of the...
Choroidal neovascularization (CNV) is a key pathological process underlying multiple retinal diseases and remains difficult to treat due to physiological barriers that limit drug delivery to the posterior segment of the eye. Current anti-vascular endothelial growth factor (VEGF) therapies rely on intravitreal injection, which is invasive and associated with potential complications. lenvatinib, a multi-targeted tyrosine kinase inhibitor, exhibits potent anti-angiogenic activity; however, its poor aqueous solubility and limited ocular bioavailability restrict its ophthalmic application. In this study, cR10-modified lenvatinib-loaded liposomes (cR10-LL) were developed to improve topical ocular delivery. The physicochemical properties, encapsulation efficiency, and stability of the liposomal formulation were systematically characterized. In vitro cellular studies demonstrated that cR10 modification significantly enhanced cellular uptake and improved the inhibitory effects on endothelial cell migration and tube formation. In a choroidal neovascularization animal model, topical administration of cR10-LL effectively suppressed neovascular lesion formation and reduced vascular leakage. Ocular distribution studies further confirmed improved drug penetration into posterior ocular tissues, while biocompatibility assessments indicated favorable safety. Overall, these results suggest that cR10-LL represent a promising non-invasive drug delivery strategy for the treatment of CNV.
Quercetin crystal-stabilized pickering emulsions: altering droplet shape via oil polarity.
Boche B, Marlot E, Faivre V … +11 more , Legrand FX, Munnier E, Boudesocque-Delaye L, Trichet M, Canette A, Domenichini S, Guiblin N, Boemare V, Zaki A, Fournier B, Huang N
Int J Pharm · 2026 Jul · PMID 42225175 · Publisher ↗
Pickering emulsions are emulsions stabilized by solid particles. These particles serve as an alternative to conventional synthetic surfactants, which may raise concerns related to toxicity, irritation, and environmental...
Pickering emulsions are emulsions stabilized by solid particles. These particles serve as an alternative to conventional synthetic surfactants, which may raise concerns related to toxicity, irritation, and environmental impact. In this study, the active pharmaceutical ingredient-traditionally solubilized or encapsulated within emulsion droplets-is instead used in its crystalline form to stabilize the droplets. Quercetin, a natural flavonoid with attractive pharmacological properties, is selected as a model compound. The effect of oil polarity on oil-in-water emulsions stabilized by size-reduced commercial quercetin dihydrate crystals is investigated. Oils of increasing polarity-PDMS, Miglyol, castor oil, a mixture of Miglyol and castor oil, and a eutectic solvent (C8:C12)-are employed. Droplet formation follows the limited coalescence phenomenon characteristic of Pickering emulsions. Increasing oil polarity leads to more deformed droplets, which nevertheless remain remarkably stable. Confocal and cryo-scanning electron microscopy (cryo-SEM) imaging confirm dense crystal coverage at the droplet interfaces for all emulsions, which remain stable for at least 28 days. This work highlights a novel strategy for the design of pharmaceutical emulsions in which natural active ingredients, in crystalline form, act as stabilizing agents, offering new perspectives for tailoring emulsion physicochemical properties.
Macrocyclic histone deacetylase inhibitor-based near-infrared-responsive ionic nanomedicines for enhanced cancer therapy.
Oyebade A, Hossain MR, Hasan M … +6 more , Oluremi A, Rahman MS, Ali N, Griffin RJ, Oyelere AK, Siraj N
Int J Pharm · 2026 Jul · PMID 42225174 · Publisher ↗
The integration of epigenetic therapy with photothermal treatment offers a promising strategy to enhance anticancer efficacy while minimizing systemic toxicity. Herein, we report the design and development of a novel cla...
The integration of epigenetic therapy with photothermal treatment offers a promising strategy to enhance anticancer efficacy while minimizing systemic toxicity. Herein, we report the design and development of a novel class of ionic nanomedicines (INMs) synthesized from macrocyclic histone deacetylase inhibitors (mac-HDACis) and Near-Infrared (NIR) dye for combination cancer therapy. The mac-HDACi components, incorporating an N-(2-aminophenyl)acylamide Zinc-Binding Group (ZBG), were first protonated using acetic acid to yield the cationic compounds of mac-para HDACi and mac-meta HDACi. Using ionic-liquid chemistry, the resulting cationic compounds were electrostatically integrated with the NIR cyanine dye IR820 anion to generate two ionic materials (IMs), which were then converted into the INMs. The INMs, [mac-para HDACi][IR820] and [mac-meta HDACi][IR820], comprise the mac-HDACis (chemotherapeutic agents) and the photothermal therapeutic dye IR820. Dynamic Light Scattering (DLS) studies showed that the INMs were well-dispersed in aqueous media, with stable particle sizes (93.1-141 nm), low polydispersity indexes (PDIs), and high negative Zeta potential (ζ) values. Photophysical studies of the INMs revealed high molar absorptivity, red-shifted absorption, and higher non-radiative rate constants (k) than the parent NIR dye, indicating a more efficient release of absorbed photon energy through non-radiative pathways. Quantitative cellular uptake measurements in the human liver cancer cell line (Hep G2) confirmed that cells exposed to INMs exhibited significantly more drug uptake than those treated with the parent NIR compound. In vitroassays in Hep G2 and MCF-7 (breast cancer) cells demonstrated that INMs exert superior cytotoxicity over parent compounds under both dark and NIR-irradiated conditions. Combination Index (CI) values < 1confirmed a synergistic effect between the HDACi epigenetic regulation and the NIR-mediated phototherapy.In addition, flow cytometry results showed that the INMs promoted apoptosis in the dark and cell necrosis under NIR irradiation, indicating a light-dependent cell death mechanism. Molecular docking study also revealed that the binding affinity for both meta and para [mac-HDACi][IR820] IMs (-9.5 kcal/mol and -9.7 kcal/mol) significantly improved as compared to the parent meta and para mac-HDACi (-7.7 kcal/mol and -7.5 kcal/mol) for human HDAC1 (PDB ID: 4BKX), a validated Class I HDAC isoform. Overall, these results demonstrate the potential of HDACi-based INMs as combination agents for targeted cancer therapy.
Evaluation of antioxidant-enriched cream formulations and their clinical effects in mild to moderate atopic dermatitis.
Celikoglu M, Vollert H, Fluhr JW … +3 more , Infante VHP, Lohan SB, Meinke MC
Int J Pharm · 2026 Jul · PMID 42225173 · Publisher ↗
Topical antioxidant-containing creams have been investigated as adjunctive treatments for atopic dermatitis, but clinical efficacy remains inconsistent. In this study, a plant extract mixture containing epigallocatechin...
Topical antioxidant-containing creams have been investigated as adjunctive treatments for atopic dermatitis, but clinical efficacy remains inconsistent. In this study, a plant extract mixture containing epigallocatechin gallate, kaempferol, quercetin, and phlorizin was incorporated into two different base formulations and compared with their respective vehicles using ex vivo, in vitro and in vivo approaches. Skin penetration was assessed by confocal Raman microscopy, formulation structure by multiphoton microscopy and clinical efficacy in patients with moderate atopic dermatitis using clinical scores, non-invasive biophysical measurements, and laser scanning microscopy. Despite significant differences in cutaneous penetration between formulations, no clinically relevant differences were observed between antioxidant-containing creams and their vehicles. The water-in-oil emulsion showed a non-significant trend toward greater improvement in pruritus and SCORAD, likely related to occlusive properties, but was not superior to the lighter formulation. Laser scanning microscopy did not demonstrate antioxidant-specific effects. Instead, formulation-dependent effects were observed, with the lighter cream tending to support deeper epidermal recovery, while more occlusive formulations mainly improved stratum corneum hydration. Overall, antioxidant enrichment did not confer additional clinical benefit beyond vehicle effects under the conditions studied. The findings highlight the dominant role of the base formulation and suggest that future studies should optimize formulation design and carefully consider disease severity to detect effects beyond vehicle-related improvements.
Non-destructive pipeline for analysis of crystalline solid dispersions.
Jorgensen C, Mbodji A, Borchardt-Setter KA … +6 more , Weichmann A, Jeffery J, Yu L, Zhang GGZ, Stelzer T, Cersonsky RK
Int J Pharm · 2026 Jul · PMID 42225172 · Publisher ↗
The continued advancement of processing technologies for pharmaceutical drug products via crystalline solid dispersion (CrySoD) requires non-invasive analytical methods capable of characterizing resultant products to und...
The continued advancement of processing technologies for pharmaceutical drug products via crystalline solid dispersion (CrySoD) requires non-invasive analytical methods capable of characterizing resultant products to understand the impact of processing choices on critical quality attributes (CQAs, e.g., crystal size, morphology, and drug content). In this study, we demonstrate a non-destructive and robust analysis pipeline using X-ray micro-computed tomography (X‑µCT) and a Python-based image-processing strategy to evaluate modafinil CrySoDs within hydroxypropyl methylcellulose (HPMC) capsules produced via solution-based additive manufacturing. X-µCT scans were first processed using radial filtration and smoothing splines to isolate the capsule object, and then the active pharmaceutical ingredient (modafinil) was isolated from the scans using greyscale thresholding based on X-µCT intensities. The CQAs were then evaluated using a combination of heterogeneity index calculations and image segmentation approaches. Watershed segmentation was most effective in crystal size analysis, as it can segment and separately characterize fused crystallites, which are well-dispersed in the capsules. Overall, this work establishes a generalizable, non-destructive workflow that might be used for the structural characterization of CrySoDs and provides a quantitative framework that links critical process parameters (CPPs) to final product CQAs.
Precise control of drying endpoint and duration in fluidized bed drying via proportional feedback: ensuring granule quality and process robustness.
Yan H, Chen H, Qiu L … +3 more , Lu L, Fang Y, Qu H
Int J Pharm · 2026 Jul · PMID 42219131 · Publisher ↗
Fluidized bed drying (FBD) is widely used in the drying of granular pharmaceuticals, but currently, manual adjustment of air intake and drying temperature is highly relied upon to control the moisture content of particle...
Fluidized bed drying (FBD) is widely used in the drying of granular pharmaceuticals, but currently, manual adjustment of air intake and drying temperature is highly relied upon to control the moisture content of particles in the fluidized bed. This manual intervention is cumbersome, labor-intensive, and limited by the thermal inertia of industrial heating systems, hindering precise control. In this study, a control system for FBD was developed to overcome this inherent challenge. The system utilizes a proportional controller to precisely control the moisture content decline trajectory of granules, and air intake flow is used as the manipulated variable. The system's robustness was evaluated using two model materials with distinct physical properties: Cordyceps Fungus Powder (high moisture) and Xin Huang Tablet powder (low moisture). Results demonstrated that the system precisely achieved the target moisture content (e.g., 6.5%) within prescribed drying durations (standard, shortened, and extended). Crucially, despite dynamic airflow adjustments, sieving analysis revealed essentially consistent particle size distributions, indicating that the strategy maintains granule integrity without causing significant attrition. The system also exhibited strong adaptability to variations in drying temperature. This approach effectively resolves the technical challenge of precise endpoint control by overcoming thermal inertia while ensuring critical quality attributes (CQAs). By enabling flexible trajectory adjustments and consistent drying rates, the proposed strategy offers a practical solution for enhancing efficiency and automation in pharmaceutical FBD processes.
Effective ropivacaine delivery using lipid nanoparticles enables simultaneous cancer therapy and pain control.
Tu X, Wang B, Tao Y … +2 more , Cai X, Chen Z
Int J Pharm · 2026 Jul · PMID 42219130 · Publisher ↗
Cancer and its associated pain pose a serious threat to human health. Cancer therapy and pain management are two distinct medical disciplines and recently proposed cancer neuroscience offers a possibility to simultaneous...
Cancer and its associated pain pose a serious threat to human health. Cancer therapy and pain management are two distinct medical disciplines and recently proposed cancer neuroscience offers a possibility to simultaneous cancer therapy and pain control. Ropivacaine (Rop), a representative local anesthetic possessing both analgesic and anti-tumor properties, emerges as an ideal agent to achieve this dual objective; however, its therapeutic potency is limited under conventional administration. Herein, a lipid nanoparticles (LNPs)-based Rop delivery system is developed to enhance its in vivo performance. Results show that obtained Rop-loaded LNPs (LNPs/Rop) are of a high drug loading efficiency (86.2 ± 5.5%), leading to a high loading capacity (17.7 ± 0.9%). The hydrodynamic diameter of LNPs/Rop is 171.1 ± 8.3 nm with negatively charged surface (-26.6 ± 2.7 mV). In vitro release assay reveals that LNPs/Rop have a high structural stability, sustainedly releasing 36.7 ± 1.7% of payload within 24 h. Cell experiments indicate that the anti-tumor potency of Rop can be significantly augmented under the co-cultured condition of neuron and tumor cells. In vivo results demonstrate that LNPs/Rop facilitate drug accumulation to target sites-dorsal root ganglion (DRG), spinal cord, and tumor. The accumulated LNPs/Rop in the nervous system effectively relieve cancer pain by blocking pain signal transduction and significantly extends the duration of action to at least 36 h, while it is less than 6 h for free Rop. Meanwhile, LNPs/Rop at a safe dose (3 mg/kg) show comparable anti-tumor potency to an equivalent dose of doxorubicin-loaded LNPs by blocking the nerve-tumor crosstalk. This work highlights a promising strategy to overcome the disconnect between cancer therapy and pain control.
Corrigendum to "Dual-Responsive multifunctional "core-shell" magnetic nanoparticles promoting Fenton reaction for tumor ferroptosis therapy" [Int. J. Pharm. 622 (2022) 121898].
Chi H, Zhu G, Yin Y … +8 more , Diao H, Liu Z, Guo Z, Xu W, Xu J, Cui C, Xing XJ, Ma K
Int J Pharm · 2026 Jun · PMID 42218850 · Publisher ↗
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Multifunctional saponin-based nanocarriers for targeting oral delivery of hydrophobic drugs: linking molecular architecture with bioavailability enhancement.
Kumar A, Rathore G, Verma A … +1 more , Singh RP
Int J Pharm · 2026 Jul · PMID 42217814 · Publisher ↗
The oral performance of Biopharmaceutics Classification System (BCS) Class II and IV drugs is primarily limited by poor aqueous solubility and intestinal efflux, resulting in low, variable absorption. Saponins, amphiphil...
The oral performance of Biopharmaceutics Classification System (BCS) Class II and IV drugs is primarily limited by poor aqueous solubility and intestinal efflux, resulting in low, variable absorption. Saponins, amphiphilic natural glycosides, have gained recognition as biogenic multifunctional excipients for integrated absorption enhancement strategies. This review synthesizes a comprehensive structure-function-bioavailability (SFB) knowledge base, relating individual saponins and derived nanocarriers' molecular architecture to micelle formation, self-assembly interactions, nanostructure formation, and quantifiable pharmacokinetic (PK) endpoints. Signalling factors including aglycone formulation type, log P, sugar chain length and branching, and HLB govern critical micellar concentration, nanostructure persistence, drug loading, cellular membrane dynamics, and modulation of intestinal efflux. Selected drug-saponin systems are used to compare diverse nanocarrier formats, for example, micelles, nano emulsions, liposomes, solid lipid nanoparticles, and silk-like nanostructures, with individual BCS Class II drugs, using both experimental and theoretical PK data. These nanocarriers achieve nanoemulsion stabilization, mucus penetration, cell membrane disruption, tight junction opening, and efflux pump inhibition, leading to significantly enhanced oral absorption (2-7 × increases in bioavailability, with dose reduction). This work defines the visualization and design rules essential to guide future nanocarrier optimization and clinical translation.
Evaluating FDM 3D printing and conventional tableting for producing ibuprofen amorphous solid dispersions.
Lesutan VN, Andersen SK, Quinten T … +1 more , Lamprou DA
Int J Pharm · 2026 Jul · PMID 42217813 · Publisher ↗
This study explored the development of an amorphous solid dispersion (ASD) of ibuprofen (IBU) with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) using single screw hot-melt extrusion (HME), for obtaining soli...
This study explored the development of an amorphous solid dispersion (ASD) of ibuprofen (IBU) with hydroxypropyl methylcellulose acetate succinate (HPMC-AS) using single screw hot-melt extrusion (HME), for obtaining solid-oral dosage forms (SODFs) with the aid of fused deposition modelling (FDM) 3D printing and conventional tabletting by direct compression, providing a head-to-head platform comparison. Pre-formulation studies identified a suitable IBU to HPMC-AS ratio for obtaining stable ASDs and allowed for the selection of HME conditions. HME was used to produce ASD filaments which were subsequently processed into solid dosage forms through 3D printing by FDM or conventional tableting by direct compression. Filaments containing HPMC-AS, IBU and additives: plasticisers (triethyl citrate (TEC) and polyethylene glycol (PEG)), superdisintegrants (Kollidon® CL), pore formers (sorbitol), or combinations of them were successfully extruded at 120-140 °C. Physicochemical characterisation confirmed IBU content and amorphisation. 3DP SODFs initially showed a slow, controlled dissolution compared to conventionally manufactured tablets; however, modifying the 3DP design to minimize print overlap and print thickness to 0.25 mm while maximizing exposed surface area, as well as adjusting the formulation, significantly improved 3D printing performance and allowed for tuning of drug release. from 5% at 60 min to 85% at 60 min. Reduced print thickness (from 0.8 to 0.25 mm) and limited print infill overlap, by using a "parallel" infill pattern rather than the commonly used "grid" infill had a greater influence on drug release than composition, for the 3DP samples, while the conventionally manufactured tablets showcased a consistent, rapid drug release. Overall, single screw HME effectively produced stable IBU:HPMCAS filaments suitable for FDM 3DP, that allowed for a tuneable drug release, offering a versatile alternative to conventional tabletting.
Novel Gemini surfactant-polyglutamic acid composite system enhances DNA delivery via a "Dual-Engine" uptake strategy.
Chen Y, Qian P, Lv J … +8 more , Gan Z, Jiang D, Xiao H, Li R, Zhang Q, Chen S, Ping Y, Chen H
Int J Pharm · 2026 Jul · PMID 42217812 · Publisher ↗
Biophysical barriers, including limited cell uptake routes and inefficient intracellular trafficking, critically restrict the efficacy of cationic gene vectors. Herein, we engineered a ternary plasmid DNA delivery platfo...
Biophysical barriers, including limited cell uptake routes and inefficient intracellular trafficking, critically restrict the efficacy of cationic gene vectors. Herein, we engineered a ternary plasmid DNA delivery platform based on a newly synthesized sulfonyl-functionalized Gemini surfactant (NGS) via electrostatic assembly with anionic γ-polyglutamic acid (γ-PGA). The optimized ternary complexes NGS-pDNA-PGA (N/P/C ratio of 5:1:1), particularly those incorporating low-molecular-weight γ-PGA (10 kDa), exhibited favorable transfection efficiency and biocompatibility both in vitro and in vivo. Unlike conventional binary NGS-pDNA complexes, which were restricted to caveolae-mediated endocytosis (CvME) and subsequent endoplasmic reticulum (ER) trafficking, γ-PGA modification introduced a "dual-engine" uptake profile, with uptake-pathway inhibition studies supporting the involvement of both caveolae-mediated and clathrin-mediated endocytosis. Further investigation revealed that this multi-route internalization led to programmed intracellular routing, utilizing both ER-dependent trafficking and lysosomal escape pathways to maximize nuclear transport. Transcriptomic analysis provided potential regulating molecules in this process. This study not only presented a high transfection efficiency, biocompatible nanocarrier but also offered a proposed framework of uptake-trafficking regulation dependent routing for next-generation nucleic acid delivery. This study provided valuable insights into the mechanisms driving the enhanced efficacy of NGS nanoparticles, offering a promising platform for transporting-regulated gene delivery.
Enzyme-powered PLGA micromotors for biofilm eradication and long-term regrowth inhibition.
Hou J, Huang Z, Jia X … +7 more , Wang J, Xu K, Fang X, Zheng Y, Qiao M, Yuan H, Meng T
Int J Pharm · 2026 Jul · PMID 42217811 · Publisher ↗
Bacterial biofilms are dense structures composed of microbial communities and their extracellular polymeric substances (EPS), posing severe challenges in the field of biomedical engineering. These EPS matrices form a "mu...
Bacterial biofilms are dense structures composed of microbial communities and their extracellular polymeric substances (EPS), posing severe challenges in the field of biomedical engineering. These EPS matrices form a "mucus protective barrier", endowing biofilms with robust resistance to antibiotics, biocides and immune responses. Conventional eradication strategies such as disinfectants and enzymatic cleaners have inherent limitations including easy induction of microbial drug resistance, failure to penetrate the EPS barrier, and inability to prevent the rapid regeneration of biofilms. In this study, a fully biodegradable enzyme-driven PLGA micromotors (PLGA MMs) system was developed via a hydroxyapatite (HAP)-stabilized oil-in-water Pickering emulsion templating method, with azithromycin (AZM) and catalase (CAT) encapsulated within the PLGA matrix. The micromotors achieve deep biofilm penetration by virtue of catalase-driven propulsive force, while the biodegradable PLGA matrix enables the sustained release of AZM for several weeks, effectively eliminating residual bacteria and inhibiting biofilm regeneration. Experimental results demonstrated that the PLGA MMs could efficiently eradicate Staphylococcus aureus biofilms (with only 3.2% residual biofilm biomass remaining), kill residual bacteria within the biofilms (with a bacterial survival rate of merely 2.3%), and completely inhibit biofilm regrowth for up to 14 days. Furthermore, the PLGA MMs exhibited favorable biocompatibility (with a CAT activity retention rate of > 88.98% and a hemolysis rate of < 5%). This synergistic "disruption-sustained inhibition" strategy provides a novel and translationally promising platform for combating recalcitrant biofilm infections.
A pH-sensitive nanococktail enabled cancer stem cell elimination, deep tumour penetration, and tumour shrinkage.
Ahmed KS, Nolan E, Wang J … +8 more , Jamieson SMF, Pan P, Mao D, Porter D, Laking G, Feng N, Shelling AN, Wu Z
Int J Pharm · 2026 Jul · PMID 42214708 · Publisher ↗
Cancer stem cells (CSCs) are intrinsically resistant to conventional therapies and play a pivotal role in cancer metastasis and recurrence. Eradication of CSCs requires combination strategies that simultaneously target m...
Cancer stem cells (CSCs) are intrinsically resistant to conventional therapies and play a pivotal role in cancer metastasis and recurrence. Eradication of CSCs requires combination strategies that simultaneously target multiple pathways at therapeutical concentrations throughout tumours. This study investigated the potential of a fusogenic pH-sensitive liposomal (pSL) nanococktail comprising doxorubicin and bufalin for targeting CSCs in clinically relevant HER2-positive breast cancer models, including cell lines (CD44 HCC1954 and CD44 BT474), homotypic and heterotypic spheroids, patient-derived organoids, and orthotopic HCC1954 mouse xenografts. At the optimal doxorubicin: bufalin ratio (10:1), the pSL-cocktail demonstrated pronounced synergistic efficacy and significantly outperformed all control formulations, including monodrug-loaded pSLs, non-pH-sensitive (DOXIL-like) liposomes, and free drugs. It significantly suppressed tumour proliferation and stemness, including CSC-associated migration, mammosphere formation, and self-renewal. In spheroids, the nanococktail rapidly penetrated to the spheroid core (≥100 µm within 1 h) and suppressed invasive dissemination. Similarly, it disrupted patient-derived organoids, achieving > 90% reduction in ATP levels and > 90% cell death. In vivo, the pSL-cocktail was well-tolerated and achieved significant tumour shrinkage, whereas DOXIL-like liposomes and free drugs showed minimal activity or severe adverse effects. Overall, this pSL-cocktail demonstrates strong potential for CSC-elimination and tumour clearance through synergistic drug combination, superior tumour penetration, and endosomal pH-triggered intracellular drug release.
Squalene-based nanostructured lipid carriers for quorum-sensing inhibitor delivery: a multifunctional platform to disrupt p. Aeruginosa biofilms and suppress virulence.
Tang D, Yu S, Zhang R … +6 more , Li N, Zhao J, Luo Y, Mao A, Liang P, Qin L
Int J Pharm · 2026 Jul · PMID 42214707 · Publisher ↗
BACKGROUND: The alarming rise of multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) demands anti-infective strategies beyond conventional antibiotics. Quorum sensing inhibitors (QSIs) represent a promising anti-v...
BACKGROUND: The alarming rise of multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) demands anti-infective strategies beyond conventional antibiotics. Quorum sensing inhibitors (QSIs) represent a promising anti-virulence approach, yet their clinical translation is often hindered by poor solubility and formulation challenges. Nanostructured lipid carriers (NLCs) represent a multifunctional platform to overcome these barriers. OBJECTIVE: Herein, we developed a squalene-based NLC encapsulating a rationally designed QS inhibitor (Y0-C10-HSL) and systematically evaluated its anti-virulence efficacy against P. aeruginosa using both in vitro and in vivo models. METHODS: Y0-C10-HSL@NLCs were prepared via high-shear homogenization coupled with probe sonication and optimized using response surface methodology based on solid-to-liquid lipid ratio, lipid-to-drug ratio, and stirring time. The optimized formulation was characterized for particle size, zeta potential, morphology, and in vitro drug release. Its anti-virulence potential was assessed through inhibition of biofilm formation, disruption of pre-established biofilms, suppression of virulence factors (pyocyanin, rhamnolipids, proteases), and impairment of bacterial motility. Therapeutic efficacy was further validated in a Caenorhabditis elegans infection model. RESULTS: The optimized formulation (solid-to-liquid lipid ratio 4:1, lipid-to-drug ratio 16:1, stirring time 26 min) exhibited an encapsulation efficiency of 61.58% and a 24 h cumulative release of 62.60%. The nanoparticles had a mean diameter of 385.90 ± 7.50 nm, a zeta potential of -22.1 ± 0.9 mV, and a PDI of 0.217. At 400 μg/mL, Y0-C10-HSL@NLCs inhibited biofilm formation by 51.99% and disrupted pre-formed biofilms by 65.42% (p < 0.001). The formulation also dose-dependently suppressed pyocyanin, rhamnolipids, and protease production, and impaired swarming, swimming, and twitching motility. In C. elegans, the formulation was non-toxic and significantly enhanced the survival of infected worms (e.g., 88.6% survival at 24 h vs. 51.1% in untreated controls), confirming its in vivo protective efficacy. CONCLUSION: Collectively, these findings establish Y0-C10-HSL@NLCs as a potent and versatile anti-virulence platform that effectively overcomes the delivery limitations of synthetic QSIs and combats P. aeruginosa infections through multi-targeted disruption of both biofilm formation and virulence.
The Colonic-PVPA: a new application of the Phospholipid Vesicle-based Permeation Assay (PVPA) as a mucus-comprising cell-free in vitro model for mucosal colonic drug delivery.
Mantegna M, Škalko-Basnet N, Flaten GE
Int J Pharm · 2026 Jul · PMID 42208826 · Publisher ↗
Colonic drug delivery has gained increasing attention as a treatment approach for both local and systemic therapy. However, the colonic mucus layer can greatly influence a drug's fate by acting as a selective barrier, fa...
Colonic drug delivery has gained increasing attention as a treatment approach for both local and systemic therapy. However, the colonic mucus layer can greatly influence a drug's fate by acting as a selective barrier, facilitating the filtration or trapping of drug molecules and carriers based on size and molecular interactions. Therefore, a simple in vitro permeability model that mimics the colonic mucus layer is essential for predicting how a drug behaves in the colon in drug development. Building on the well-established, easy-to-use, cost-effective, and cell-free in vitro model Phospholipid Vesicle-based Permeation Assay (PVPA), the Colonic-PVPA was developed by incorporating the Porcine Artificial Colonic Mucus (PACM). After verifying the barrier's integrity in the presence of the PACM, the impact of biosimilar mucus on drug permeation was investigated using six model drugs and compared to the previous generation of PVPA in the absence and presence of hydrated mucins (Mucus-PVPA). The Colonic-PVPA successfully distinguished compounds from different BCS classes and with physicochemical properties, while hindering their permeation across the barrier due to the presence of the biosimilar mucus. Additionally, the interaction between the mucus layer and mucointeracting formulations has been assessed through the Colonic-PVPA, confirming the model's usefulness in formulation development of mucoadhesive (chitosan-coated) and mucopenetrating (PEGylated) nanoparticles. In all cases, significant differences between Mucus-PVPA and Colonic-PVPA were observed, highlighting the importance of mucus composition in drug permeation. Overall, the Colonic-PVPA proves to be a promising in vitro model that resembles the colonic environment, making it suitable for drug permeability screening and formulation development.
The effect of spray properties and inspiratory flow rate on regional nasal deposition for pressure-swirl versus soft mist devices.
Fong TYA, Thirugnanasampanthar M, Iley T … +2 more , Parry M, Forbes B
Int J Pharm · 2026 Jul · PMID 42208825 · Publisher ↗
Effective nasal drug delivery requires an understanding of the factors that govern spray performance and regional nasal deposition. This study evaluated the effects of inspiratory flow, formulation viscosity, and device...
Effective nasal drug delivery requires an understanding of the factors that govern spray performance and regional nasal deposition. This study evaluated the effects of inspiratory flow, formulation viscosity, and device configuration on spray characteristics and regional nasal deposition. Low- (0.9 cP) and high-viscosity (4.0 cP) formulations were delivered using pressure-swirl, soft mist, and a syringe-coupled soft mist configuration under modified actuation conditions. Regional nasal and inhaled deposition fractions were quantified using the Alberta Idealised Nasal Inlet coupled to the Next Generation Impactor, operated under resting (7.5 L/min) and sniff-like (30 L/min) inspiratory flow. The highest vestibular deposition fraction (59.1%) occurred under resting inspiratory flow for the high-viscosity formulation delivered by the pressure-swirl device, consistent with enhanced inertial impaction of larger droplets. The highest turbinate deposition fraction (84.1%) occurred under sniff-like inspiratory flow for the high-viscosity formulation delivered by the syringe-coupled soft mist configuration. The olfactory deposition fraction was minimal (≤ 1.1%) across all conditions. The pressure-swirl device produced larger droplets and greater vestibular deposition under resting inspiratory flow. The soft mist platform generated smaller droplets, while the syringe-coupled soft mist configuration achieved the highest turbinate deposition under sniff-like inspiratory flow. These findings suggest droplet inertia (modulated by formulation viscosity and device atomisation mechanism) and airflow-driven entrainment (modulated by inspiratory flow) govern regional nasal deposition.
Injectable and degradable hydrogel: in vitro drug release behavior and evaluation in a brain repair context.
Park S, Pin-Barre C, Luzel B … +6 more , Cousinie S, Garrigue P, Pellegrino C, Gigmes D, Laurin J, Trimaille T
Int J Pharm · 2026 Jul · PMID 42208824 · Publisher ↗
Injectable hydrogels are attractive for tissue engineering due to their minimally invasive administration and their ability to provide localized and controlled drug delivery. In this study, we investigated an amphiphilic...
Injectable hydrogels are attractive for tissue engineering due to their minimally invasive administration and their ability to provide localized and controlled drug delivery. In this study, we investigated an amphiphilic PNIPAAm-b-PLA-b-PEG-b-PLA-b-PNIPAAm pentablock copolymer hydrogel, previously developed as a thermoresponsive system forming via intermicellar bridging at physiological temperature. Its capacity to load and release neuroprotective drugs with distinct physicochemical properties was evaluated. Hydrophobic (riluzole) and hydrophilic (minocycline, apelin-13) model drugs were incorporated, and in vitro release profiles were monitored under physiological conditions. Drug release behavior depended on drug hydrophobicity: hydrophilic compounds exhibited rapid, diffusion-driven release with a pronounced burst effect, whereas the hydrophobic drug showed a slower and more sustained release, correlated with hydrogel degradation (mass loss) at low drug loadings. The hydrogel showed no detectable cytotoxicity toward neuronal cells in vitro. In addition, hydrogel-mediated drug delivery modulated cellular responses depending on the compound, reducing the cytotoxic effects of minocycline and enhancing neuronal survival in the presence of apelin. Importantly, hydrogel-mediated delivery enabled modulation of drug exposure kinetics, thereby influencing the resulting cellular responses. Altogether, these results highlight the ability of this thermoresponsive hydrogel to accommodate drugs with diverse physicochemical properties and to modulate their release and associated biological effects, supporting its relevance as a platform for controlled delivery of neuroactive compounds.
Kartogenin-Loaded Selenium-Prussian Blue Nanogel through ROS scavenging and cartilage regeneration for the mitigation of osteoarthritis.
Song Y, Zhu X, Yu N … +6 more , Bian X, Yang D, Ma L, Zhang M, Yang J, Zuo W
Int J Pharm · 2026 Jul · PMID 42203085 · Publisher ↗
Osteoarthritis (OA), a degenerative joint disease driven by synovial inflammation, oxidative stress and progressive cartilage degradation, remains a major clinical challenge. While drug-loaded nanozymes offer an effectiv...
Osteoarthritis (OA), a degenerative joint disease driven by synovial inflammation, oxidative stress and progressive cartilage degradation, remains a major clinical challenge. While drug-loaded nanozymes offer an effective strategy for OA treatment by scavenging reactive oxygen species (ROS) and delivering therapeutics, their efficacy is limited by insufficient catalytic activity and poor drug retention capacity. Herein, we developed a specific matrix metalloproteinase (MMP) 13-responsive smart nanogel system (M-MA@KSPB) comprising a selenium-doped Prussian blue nanozyme (SPB) core loaded with kartogenin (KGN) and an MMP13-responsive peptide cross-linking hyaluronic acid methacryloyl (HAMA) shell. As MMP13 is a key biomarker of OA progression, the MMP13-triggered responsiveness of M-MA@KSPB enhanced its retention within the joint cavity through targeted structural changes, thereby enabling spatiotemporally precise KGN release for cartilage regeneration. Upon release, the SPB nanozyme exhibited catalase (CAT)-, superoxide dismutase (SOD)-, and glutathione reductase (GR)-like activities, potently scavenging ROS and mitigating oxidative stress. Furthermore, the M-MA@KSPB downregulated pro-inflammatory cytokines (TNF-α, IL-6), while enhancing collagen II synthesis and suppressing MMP13 expression in Lipopolysaccharide (LPS)-stimulated chondrocytes. In a post-traumatic OA rat model, this system inhibited joint inflammation and osteophyte formation, concurrently promoting cartilage regeneration and restoring anabolic/catabolic balance through KGN-mediated repair. This nanogel system offers a new OA treatment strategy by combining anti-oxidative stress therapy with cartilage repair.
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