Int J Pharm [JOURNAL]
Sun
200 papers
Nanomedicines targeting matrix metalloproteinases for osteoarthritis treatment.
Ma X, Zhang Y, Li J … +3 more , Meng Y, Zhang N, Shang H
Int J Pharm · 2026 Jul · PMID 42264232 · Publisher ↗
Osteoarthritis (OA) is a frequently diagnosed joint disease. It is characterized by articular cartilage/bone damage, synovitis, pain, etc., which severely reduce the life quality of patients. Current treatments for OA ac...
Osteoarthritis (OA) is a frequently diagnosed joint disease. It is characterized by articular cartilage/bone damage, synovitis, pain, etc., which severely reduce the life quality of patients. Current treatments for OA act to reduce inflammation and lubricate joints but barely halt OA progression and joint damage. Matrix metalloproteinases (MMPs) are key factors for extracellular matrix (ECM)/cartilage/bone degradation and inflammation. Therapies targeting MMPs hold the potential to treat OA efficiently. Recently, MMPs have been studied as the therapeutic targets for OA treatment. MMP inhibitors, gene therapies for MMP silencing, and biological agents for MMP clearance are continuously reported. However, these therapies are limited by short intra-articular drug retention, insufficient joint targeting, low bioavailability, etc. To solve these issues, nanomedicines have been reported to improve MMP-targeted therapies. To highlight the advances in this field, this review first introduces the key subtypes and biological roles of MMPs in OA pathogenesis. It then summarizes the reported MMP-targeted therapies and the advanced nanomedicines that improved the MMP-targeted therapies. Finally, it discusses the mechanisms, progress, issues, and the future perspectives of the nanomedicines for the MMP-targeted therapies.
Establishing experimental parameters for biphasic transfer in vitro lipolysis model.
Kirschbaum HS, Jede C, Koehl LJ … +5 more , Kuentz M, Holm R, Griffin BT, Blechar JA, ÓDwyer PJ
Int J Pharm · 2026 Jul · PMID 42264231 · Publisher ↗
Lipid-based-formulations (LBFs) are widely used to improve oral bioavailability of poorly water-soluble drugs. Despite their widespread use in predicting formulation performance, standard in vitro lipolysis assays often...
Lipid-based-formulations (LBFs) are widely used to improve oral bioavailability of poorly water-soluble drugs. Despite their widespread use in predicting formulation performance, standard in vitro lipolysis assays often lack an absorptive sink and fail to capture the transition from gastric to intestinal environments, thereby reducing their predictive relevance for in vivo outcomes. The aim of this study was to develop a biphasic in vitro lipolysis model incorporating an absorptive sink. This might offer the potential to increase the predictive power of in vitro digestion models in the future. In this model, the absorptive sink was provided by a decanol layer, and to simulate gastrointestinal transit, two dynamic pH-transition approaches were employed: a biphasic GI-transfer model and a biphasic pH-shift model. Using nilotinib-loaded LBFs, the study established conditions for this biphasic system and examined how media composition and lipase source influence drug concentrations during formulation dispersion, digestion, and partitioning into the organic sink. The results showed that digestion experiments conducted with either porcine pancreatin or Palatase® 20000 L increased the concentration of nilotinib in the aqueous digestion medium, which correspondingly reduced partitioning of the drug into the decanol layer. For the readily dispersible Type III LBF in the biphasic GI-transfer setup, nilotinib permeation into the decanol layer decreased compared with a lipid-free control, likely due to improved drug solubilization in the aqueous digestion phase. In contrast, the poorly dispersible Type I LBF was better suited to the biphasic pH-shift setup, but it showed higher drug levels in the decanol layer, reflecting rapid partitioning of lipids-and associated crystalline drug-into the organic phase. Overall, this study establishes suitable conditions for evaluating the lipolysis of LBFs during a dynamic pH transition in the presence of an absorptive sink. This advanced approach provides additional insight to explore digestion-mediated and/or pH-mediated supersaturation during digestion of LBFs.
Ritonavir release from spherical amorphous solid dispersions: prediction and observation.
Men S, Treffer D, Polli JE
Int J Pharm · 2026 Jul · PMID 42264230 · Publisher ↗
Solvent penetration was previously identified and modeled as the dominant rate-limiting step in ritonavir (RTV) release from amorphous solid dispersion (ASD) discs composed of poly(vinylpyrrolidone-co-vinyl acetate) (PVP...
Solvent penetration was previously identified and modeled as the dominant rate-limiting step in ritonavir (RTV) release from amorphous solid dispersion (ASD) discs composed of poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA). In this study, drug release from discs was extended to spherical ASD particles. RTV/PVPVA ASDs with drug loadings of 5-25% were fabricated using vacuum compression molding (VCM) with a custom free-D mold to produce 1 mm and 5 mm spherical particles. The solvent penetration rates (dd/dt) across drug loadings (DLs), measured from discs under a microscope-enabled disc dissolution system (MeDDiS), were assumed to be an intrinsic and geometric-independent parameter and were directly applied to a spherical particle dissolution model. Dissolution studies were conducted under small-volume (20 mL) conditions for 1 mm particles and USP II conditions (900 mL) for 5 mm particles, including both single and multiple particle systems. Predicted dissolution profiles showed good agreement with experimental data across sphere diameter and the number of spheres undergoing dissolution. Overall, the results demonstrate the transferability of solvent penetration rate from discs to spherical particles and confirm that dissolution of RTV/PVPVA ASDs at low drug loadings [i.e., before reaching the limit of congruency (LoC)] was primarily governed by solvent penetration.
From R&D to production: Scale-out of continuous spin-freeze-drying for a PEGylated peptide formulation.
Schaal Z, Leys L, Bockstal PV … +3 more , Funke AP, Schneid SC, Beer T
Int J Pharm · 2026 Jul · PMID 42264057 · Publisher ↗
Scale-out is critical for translating continuous spin-freeze-drying from development to GMP-relevant manufacturing. In this study, a continuous spin-freeze-drying process for a model PEGylated peptide formulation was tra...
Scale-out is critical for translating continuous spin-freeze-drying from development to GMP-relevant manufacturing. In this study, a continuous spin-freeze-drying process for a model PEGylated peptide formulation was transferred from a single-vial-lab-scale R&D unit (RheaLyo™ Mono) to a GMP-compatible prototype line (GMP-Flex™). Identical spin-freezing and drying settings were applied on both platforms to directly assess the reproducibility of process performance during scale-out. Product temperature profiles during freezing and drying aligned closely between RheaLyo™ Mono and GMP-Flex™, indicating comparable thermal histories across scales. Product quality was assessed by cake appearance, residual moisture content, peptide concentration by RP-HPLC and monomer levels by SEC. All samples formed intact cakes without signs of collapse and maintained monomer levels close to 100 percent, indicating no detectable aggregation upon transfer. Residual moisture contents for both platforms were within the same overall range and met the predefined target of 0.3-0.6%. Residual moisture levels on the GMP-Flex™ prototype showed no timing-dependent trend over the production run, confirming stable, steady-state drying performance throughout continuous production. Overall, these results demonstrate for the first time the successful scale-out of continuous spin-freeze-drying under the matched process conditions while maintaining consistent product quality.
Targeted delivery of kaempferol via mannose-modified PLGA nanoparticles reprograms macrophages and ameliorates rheumatoid arthritis.
Zhang Z, Yuan S, Ouyang Y … +10 more , Zou J, Liu Z, Li X, Wang Z, Zhang Y, Feng X, Fang Q, Yao J, Wang T, Zhang X
Int J Pharm · 2026 Jul · PMID 42264056 · Publisher ↗
BACKGROUND: While the natural flavonoid Kaempferol (Kae) possesses promising anti-inflammatory and immunomodulatory properties for treating rheumatoid arthritis (RA), it is challenged by poor aqueous solubility and low b...
BACKGROUND: While the natural flavonoid Kaempferol (Kae) possesses promising anti-inflammatory and immunomodulatory properties for treating rheumatoid arthritis (RA), it is challenged by poor aqueous solubility and low bioavailability, which impede its targeting of key effector cells like macrophages and limit its clinical utility. PURPOSE: To overcome Kae's pharmaceutical limitations in RA therapy, We developed mannose-modified PLGA nanoparticles (Kae-NPs) for macrophage-targeted delivery and investigated their therapeutic efficacy and underlying mechanisms. METHODS: Integrated bioinformatic analyses of GEO datasets identified macrophage-related pathways as central to rheumatoid arthritis (RA) pathogenesis. Kae-NPs were synthesized and evaluated for their morphology, size distribution, surface charge, and drug-release profile. Cellular uptake and macrophage polarization were assessed in LPS-treated RAW264.7 cells by flow cytometry, ELISA, and immunofluorescent staining. In a collagen-induced arthritis (CIA) rat model, therapeutic efficacy and mechanisms were evaluated through small-animal imaging, micro-CT, histopathology, and serum immune profiling. RESULTS: Kae-NPs showed uniform size (∼136 nm) and sustained release. They were efficiently internalized by macrophages and promoted M1-to-M2 polarization in vitro. In CIA rats, Kae-NPs accumulated in inflamed joints, reduced swelling, cartilage damage, and bone erosion. Mechanistically, Kae-NPs scavenged ROS, modulated cytokine production by suppressing IL-6, IL-1β and TNF-α while elevating TGF-β and IL-10, restored Treg/Th17 balance, and inhibited fibroblast-like synoviocyte (FLS) proliferation, with no systemic toxicity observed. CONCLUSIONS: Kae-NPs enable targeted Kae delivery to joint macrophages, ameliorating RA through ROS clearance, macrophage reprogramming, and immune homeostasis restoration, offering a promising nanotherapeutic strategy.
Discrimination of crystal polymorphism in active pharmaceutical ingredients using time-domain H NMR relaxation combined with multivariate statistical process control.
Yusuke M, Oishi T, Hara A … +4 more , Katsumata T, Kumada S, Okada K, Onuki Y
Int J Pharm · 2026 Jun · PMID 42264055 · Publisher ↗
This study investigated the feasibility of evaluating crystal polymorphs of active pharmaceutical ingredients (APIs) using H NMR relaxation measurements with time-domain NMR (TD-NMR). Desloratadine, linagliptin, and carb...
This study investigated the feasibility of evaluating crystal polymorphs of active pharmaceutical ingredients (APIs) using H NMR relaxation measurements with time-domain NMR (TD-NMR). Desloratadine, linagliptin, and carbamazepine, each exhibiting multiple polymorphic forms, were selected as model APIs. T relaxation times were measured, and the results showed that T relaxation behavior differed for each crystal form of the APIs. For desloratadine, an amorphous sample was also prepared and evaluated. It was demonstrated that the T relaxation time of the amorphous form was shorter than those of the crystal polymorphs, indicating higher molecular mobility. T relaxation curves were further analyzed using multivariate statistical process control (MSPC) based on principal component analysis, and Hotelling's T² and Q statistics successfully distinguished different crystalline forms. In the latter part of this study, physical mixtures of crystal polymorphs were tested to evaluate the detection sensitivity of the MSPC approach. The results demonstrated that this method could identify polymorphic admixtures with a detection limit of approximately 5-10%, depending on the API. TD-NMR offers practical advantages, including rapid measurement, minimal sample preparation, and non-destructive analysis using low-field benchtop instruments. These results indicate that TD-NMR combined with MSPC provides a practical at-line method for monitoring crystal polymorphism and detecting polymorphic contamination during pharmaceutical manufacturing.
Enhanced intestinal mucosal retention via polypseudorotaxane-microsheets for oral drug delivery.
Yao C, Cai S, Huang Y … +6 more , An P, Mao C, Huang T, Ying Y, Ye L, Mu C
Int J Pharm · 2026 Jul · PMID 42264054 · Publisher ↗
Oral delivery is the most acceptable administration route. However, the intestinal mucus layer remains the major barrier that prevents intact drug carriers from contacting epithelial cells and entering the systemic circu...
Oral delivery is the most acceptable administration route. However, the intestinal mucus layer remains the major barrier that prevents intact drug carriers from contacting epithelial cells and entering the systemic circulation. The geometry of oral nano/micro-carriers plays a key role in affecting the mucus permeation and transmembrane transport so as to prolong intestinal residence and enhance epithelium traversal. Here, polypseudorotaxane microsheets (PPRMs) with different side lengths and thicknesses were fabricated via host-guest inclusion between β-cyclodextrin and short-chain diblock surfactants. PPRMs have good structural stability in simulated gastrointestinal fluids and intestinal mucus conditions. PPRMs exhibited typical controlled release characteristics in simulated mucus layer. Among the four PPRMs, OP10-PPRM shows superior mucoadhesive capability toward the intestinal mucus layer due to their favorable wettability and small side length. Three types of PPRMs enhance the penetration depth into intestinal mucus, and OP10-PPRM also prolongs the intestinal retention time in vivo. The payloads in PPRMs could either be released after dissociation or internalized into epithelial cells with intact form. Overall, PPRMs as drug nano/micro-carriers can effectively enhance intestinal mucosal retention and overcome oral drug delivery barrier owing to their geometrical advantages.
Targeting cutaneous inflammation: A review on advanced topical delivery systems and precision medicine in psoriasis.
Bobde M, Purohit A, Nema P … +4 more , Sahu A, Kashaw V, Soni V, Kashaw SK
Int J Pharm · 2026 Jul · PMID 42264053 · Publisher ↗
Psoriasis is a chronic autoimmune-mediated inflammatory skin disorder that is characterized by increased keratinocyte proliferation, abnormalities in the immune system, and abnormalities in the epidermal barrier. The con...
Psoriasis is a chronic autoimmune-mediated inflammatory skin disorder that is characterized by increased keratinocyte proliferation, abnormalities in the immune system, and abnormalities in the epidermal barrier. The conventional topical treatments for the management of psoriasis include corticosteroids, vitamin D analogues, and keratolytic. The long-term efficacy of these topical treatments for the management of psoriasis is marred by issues such as skin penetration difficulties, side effects, tachyphylaxis, and poor patient compliance. In recent times, nanotechnology-based drug delivery systems such as liposomes, transferosomes, ethosomes, solid lipid nanoparticles, nanostructured lipid particles, and nano emulsions have been identified as potential therapeutic tools for the management of psoriasis. The nanotechnology-based drug delivery system has the potential to improve the solubility of the drug, permeability of the drug through the stratum corneum layer of the skin, and release and retention of the drug in the skin layer. In addition, the recent trends in the management of psoriasis have opened new avenues for the management of this condition. The review article discusses the pathology of psoriasis, the current treatment options for the management of psoriasis, and the recent advances in nanotechnology-based topical drug delivery for the management of psoriasis.
Advanced therapeutic strategies and drug delivery approaches for management of oral submucosal fibrosis: a comprehensive review.
Kotian M, Mehta CH, Nayak Y … +1 more , Nayak UY
Int J Pharm · 2026 Jul · PMID 42252034 · Publisher ↗
Oral Submucous Fibrosis (OSF) is a chronic, progressive, and potentially malignant oral mucosal disorder that leads to development of trismus, burning sensations, mucosal blanching, and impaired oral function. Traditiona...
Oral Submucous Fibrosis (OSF) is a chronic, progressive, and potentially malignant oral mucosal disorder that leads to development of trismus, burning sensations, mucosal blanching, and impaired oral function. Traditional treatments of OSF, including corticosteroids, hyaluronidase, antioxidants, and surgery, are limited due to poor drug delivery, systemic toxicity, and patient non-compliance. In this current scenario, the development of an advanced drug delivery system can be a potential strategy for OSF therapy, and emerging drug delivery strategies offer promising solutions by enabling localised, targeted, and sustained therapy. Novel drug delivery systems include Nanocarriers, Electrospun nanofibers, Mucoadhesive buccal patches, Microneedle systems, Biomaterial-based hydrogels, Stem cell-derived exosomes and many others, which help to provide the drug concentration at the target site for a longer time and give therapeutic effects that improve patient compliance by increasing the efficacy of the formulations for OSF treatment. Hydrogels, microneedle systems, and injectable therapies (e.g., hyaluronidase-dexamethasone, sodium hyaluronate with bioglass) provide regenerative, sustained, and minimally invasive treatment options with fewer adverse effects. Emerging approaches like stem cell-derived exosomes and gene therapy (miRNA-loaded nanoparticles) target fibrogenic pathways, reversing fibrosis and offering novel regenerative strategies. This review focuses on nanotechnology-based, mucoadhesive, injectable, and transmucosal delivery systems for managing OSF, highlighting targeted, persistent treatments by combining advanced drug-delivery systems. The study examines regenerative medicines, like exosomes and microRNA delivery methods, while providing insights into site-specific drug distribution and carrier optimization. Despite promising advancements, further clinical trials, safety data, and standardized guidelines are needed, and the OSF treatments should emphasize individualized, biomarker-guided approaches.
Dairy industry side-stream lactose as a surrogate for commercial products during major supply disruptions.
Ng CX, Junnila A, Kemell M … +5 more , Moilanen U, Teppo J, Tossavainen M, Peltonen L, Karttunen AP
Int J Pharm · 2026 Jul · PMID 42252033 · Publisher ↗
Drug shortages are a current issue and often originate from problems in raw material supply. Even though they are more related to active ingredients the reason could be the lack of excipient(s) due to a major disruption...
Drug shortages are a current issue and often originate from problems in raw material supply. Even though they are more related to active ingredients the reason could be the lack of excipient(s) due to a major disruption to normal supply chains. Lactose is one of the most used excipients in oral solid dosage forms such as tablets. The aim of this study was to utilize lactose from a dairy side-stream in wet granulation and tableting and evaluate its behaviour in a formulation in comparison to a commercial reference. The possibility to use this type of lactose would be a sustainable option to ensure domestic availability during crises. The study design included different lactose proportions of fillers as well as liquid to solid ratios to investigate whether the resulting granules show similar responses when using side-stream or commercial lactose. The responses to changes were rather similar regardless of the lactose grade but liquid to solid ratio needed to be decreased (0.6 to 0.8. vs. 0.4 to 0.6) when using side-stream lactose. The formulations using side-stream lactose exhibited adequate flowability (3rd best classification in Ph.Eur) which was slightly inferior to that with commercial but tabletability was better due to its amorphous nature. However, disintegration (about 20 min vs. 2 min) and drug release (60-80 % vs. 100 %) were slower when using the side-stream lactose. This was most likely due to remaining milk proteinsin the lactose. Overall, the side-stream lactose provided promise for the use of such a side-stream material during supply disruptions.
Electrospun PCL/PVA core-sheath nanofibres enabling staged antibiotic and peptide delivery for diabetic foot ulcer dressings.
Lian S, Irwin R, Wylie MP … +2 more , Zhao M, Lamprou DA
Int J Pharm · 2026 Jul · PMID 42252032 · Publisher ↗
Diabetic foot ulcers (DFUs) require rapid infection control alongside sustained regenerative signalling; however, co-delivery is hindered by different release requirements and peptide instability. A dual-compartment core...
Diabetic foot ulcers (DFUs) require rapid infection control alongside sustained regenerative signalling; however, co-delivery is hindered by different release requirements and peptide instability. A dual-compartment core-sheath dressing was fabricated by coaxial electrospinning, comprising a poly(ε-caprolactone) (PCL) shell loaded with levofloxacin (LEV) and a poly(vinyl alcohol) (PVA) core encapsulating either insulin or calcitonin gene-related peptide (CGRP). Microscopy confirmed uniform, bead-free fibres with a well-defined core-sheath architecture. Encapsulation efficiencies were 92.97 ± 6.72% and 93.36 ± 5.36% for LEV, and 82.82 ± 12.46% (insulin) and 83.76 ± 8.25% (CGRP) for the peptide payloads. Drug loading improved mechanical performance, increasing the ultimate tensile strength from 7.05 ± 1.16 MPa (blank) to 8.80 ± 1.12 MPa (insulin) and 11.80 ± 1.63 MPa (CGRP). In phosphate-buffered saline (37 °C, pH 7.4), shell-loaded LEV showed a rapid (>91% within 4 h; ∼96-98% by 8 h), whereas core-loaded insulin and CGRP were released over 7 days, reaching 88.05 ± 2.89% and 90.12 ± 5.71% cumulative release, respectively. Free-peptide controls exhibited marked time-dependent loss in measurable concentration, consistent with reduced apparent peptide loss during fibre-mediated release. LEV-loaded mats produced clear zones of inhibition against Staphylococcus aureus and Escherichia coli throughout 7 days. In this in vitro proof-of-concept study, this modular coaxial platform decouples antibiotic and peptide delivery to support sequential management of infection and tissue repair in infected chronic wounds, with diabetic foot ulcers as the intended clinical context.
Triboelectric effect on the adhesive coating of particles in a high shear mixer.
Wang Y, Chan HK, Yang R
Int J Pharm · 2026 Jul · PMID 42250661 · Publisher ↗
Adhesive dry powder coating is widely applied in pharmaceutical and particulate processing. Achieving a uniform distribution of fines of active pharmaceutical ingredient (API) on carrier surfaces remains challenging due...
Adhesive dry powder coating is widely applied in pharmaceutical and particulate processing. Achieving a uniform distribution of fines of active pharmaceutical ingredient (API) on carrier surfaces remains challenging due to complex particle-particle and particle-wall interactions. This study employs the discrete element method (DEM) coupled with a triboelectrification model to investigate the dynamics and electrification mechanisms governing adhesive mixing in a high-shear mixer. The particle motion, charge evolution, and their combined influence on coating performance are analysed. Results show that while electrostatic forces have minimal impact on particle velocity and power draw, they exert a pronounced effect on mesoscale mixing behaviour. Bipolar charging among carriers leads to strong spatial heterogeneity, causing fines to concentrate locally and substantially reducing coating uniformity. Modifying the impeller and vessel surfaces using materials with work functions closer to that of fines causes favourable charge transfer and enhances coating uniformity. On the other hand, increasing the impeller rotational speed increases the specific charge level of fines, intensifies charge-driven segregation, and results in less uniform API attachment. The study highlights the critical role of electrostatics in adhesive mixing and demonstrates how controlling wall work function and rotational speed can significantly improve mixture homogeneity.
pH/enzyme dual-responsive nanoparticles hitchhike neutrophils to enhance bacteria-induced acute lung infection treatment.
Qin L, Li X, Sun J … +9 more , Li Y, Li A, Xing X, Wen C, Chen Y, He Y, Wang J, Li J, Zhang CY
Int J Pharm · 2026 Jul · PMID 42250660 · Publisher ↗
Acute lung infection (ALI) represents a major global health challenge with high morbidity and mortality. The current clinical approach primarily relies on antibiotic therapy, yet the therapeutic efficacy is severely limi...
Acute lung infection (ALI) represents a major global health challenge with high morbidity and mortality. The current clinical approach primarily relies on antibiotic therapy, yet the therapeutic efficacy is severely limited by poor drug targeted delivery. Here, we developed neutrophil-hijacking pH/enzyme dual-responsive rifampicin-loaded nanoparticles (RFP‑NENPs) composed of pH-sensitive polymer (mPEG-PAE) and enzyme-responsive polymer PCL-PEG decorated with neutrophil elastase-targeting peptide, which can self-assemble into nanoparticles. After intravenous injection, the RFP‑NENPs can specifically target and hijack neutrophils in vivo, and deposit at the infectious site due to inflammatory chemotaxis of pro-inflammatory neutrophils via the immune response, followed by releasing the cargos due to the low pH and bacterial enzymes in the infectious microenvironment. In a mouse model of acute lung infection by Staphylococcus aureus, RFP‑NENPs effectively cleared the bacteria and caused no detectable systemic toxicity. This work not only presents an effective therapeutic for enhanced acute lung infection treatment, but also offers a neutrophil-mediated drug delivery strategy.
Smart single hollow magnetothermal nanorings with phase change materials for controlled drug release and negative MRI guided cancer therapy.
Bao J, Guo S, Ren Y … +12 more , Cheng J, Yang Y, Zhang Y, Tu H, Wang J, Fan D, Zhuang Y, Dong Y, Tulupov A, Wang X, Ma X, Zhang Y
Int J Pharm · 2026 Jul · PMID 42248223 · Publisher ↗
Magnetic hyperthermia therapy (MHT) for tumors is alocalized, minimally invasive, and deeply penetrating treatment, but it faces limitations such as low magnetothermal conversion efficiency, strict safety thresholds for...
Magnetic hyperthermia therapy (MHT) for tumors is alocalized, minimally invasive, and deeply penetrating treatment, but it faces limitations such as low magnetothermal conversion efficiency, strict safety thresholds for magnetic field intensity, and the inability of single-mode magnetic hyperthermia to completely eradicate tumors. In this work, we develop an innovative, thermoresponsive drug-delivery platform composed of single hollow magnetic vortex iron oxide nanorings (MVIONs) coated with phase-change materials (PCM), designated MVIONs@PCM. Under an alternating magnetic field (AMF), MVIONs efficiently generate heat, triggering the melting of the PCM shell and releasing co-encapsulated anticancer drugs in a controlled, "on/off" manner. In vitro experiments confirm the exceptional thermal induction capacity of MVIONs@PCM, yielding a specific absorption rate of 1058.68 W·g at 600 Oe, sufficient to produce robust hyperthermia effects. Additionally, this nano platform exhibits very low basal release without AMF activation. MVIONs@PCM also achieves strong negative magnetic resonance imaging (MRI) contrast, with a high transverse relaxivity (R = 45.986 mM·s) even at 0.5 T, supporting real-time treatment guidance and monitoring. Combining magnetic hyperthermia and AMF-induced chemotherapy significantly enhances tumor growth inhibition. This multifunctional platform represents a promising strategy for MRI-guided magnetothermal chemotherapy.
Mesalamine colon-retentive microparticles for treatment of ulcerative colitis.
Meng T, Zeng J, Zhu Y … +5 more , Ai J, Lin Z, Luo Y, Yuan H, Hu F
Int J Pharm · 2026 Jul · PMID 42248222 · Publisher ↗
Ulcerative colitis (UC) is a lifelong inflammatory disease affecting the rectum and colon. Mesalazine (MSZ) is the first-line clinical treatment for UC but has a short half-life of 0.5 to 2 h, necessitating multiple dail...
Ulcerative colitis (UC) is a lifelong inflammatory disease affecting the rectum and colon. Mesalazine (MSZ) is the first-line clinical treatment for UC but has a short half-life of 0.5 to 2 h, necessitating multiple daily doses. Moreover, most of the drug is absorbed in the stomach and small intestine, resulting in low drug concentrations at the lesion site and limited therapeutic efficacy. Herein, we developed a coating material mannosylated ethyl cellulose (Man-EC) to confer colon-retentive properties to MSZ microparticles by leveraging the adhesive property of mannose to macrophages at the UC site. MSZ microparticles with high mechanical strength, good roundness, and a particle size below 200 μm were prepared using a water-in-oil-in-water (W/O/W) double emulsion method. A sustained-release layer of Man-EC and an enteric coating of Eudragit S100 were sequentially applied to the particle surface, yielding fine-sized enteric sustained-release microparticles with colon-retentive properties. Upon dissolution of the enteric coating in the colon, mannose on the microparticle surface is exposed and binds to mannose-related receptors on macrophages at the UC site. This adhesion enables the microparticles to remain at the colonic lesion site and slowly release the encapsulated MSZ, achieving sustained drug delivery for enhanced local therapy.
Leukocyte-mimicking nanoparticles for enhanced synovial targeting in autoimmune arthritis.
Mirbolouk M, Sohail M
Int J Pharm · 2026 Jul · PMID 42248221 · Publisher ↗
Conventional systemic therapy for rheumatoid arthritis (RA) is limited by poor synovial drug accumulation, rapid systemic clearance, and dose-dependent off-target toxicities. Although inflamed joints may permit partial p...
Conventional systemic therapy for rheumatoid arthritis (RA) is limited by poor synovial drug accumulation, rapid systemic clearance, and dose-dependent off-target toxicities. Although inflamed joints may permit partial passive nanocarrier accumulation, increased accumulation in the joints remains heterogeneous and often insufficient for reliable therapeutic delivery. Leukocyte-mimicking nanoparticles (LM-NPs) therefore represent a promising active targeting strategy for autoimmune arthritis by recapitulating key elements of leukocyte trafficking, including selectin-mediated rolling, integrin-dependent adhesion, chemokine-guided migration, and immune-evasive self-signaling, thereby constructing an unparalleled biomimetic targeting system. By incorporating leukocyte-derived membranes, membrane-derived vesicles, or leukocyte-inspired surface ligands, these platforms are designed to improve vascular engagement, synovial localization, joint retention, and payload delivery. Preclinical arthritis studies suggest that LM-NPs can enhance joint accumulation and therapeutic efficacy for small molecules, biologics, and nucleic-acid therapeutics while reducing systemic exposure relative to non-biomimetic nanoparticles or free-drug formulations. However, the current evidence base is stronger for neutrophil-mimetic systems than for macrophage-mimetic or hybrid platforms, and direct head-to-head comparisons remain limited. This review analyzes the design principles, trafficking mechanisms, preclinical evidence, and translational barriers of LM-NPs in autoimmune arthritis, with emphasis on how biomimetic engineering can complement passive inflammatory targeting. We further discuss unresolved challenges related to immunogenicity, manufacturing scalability, reproducibility, regulatory classification, and comparative benchmarking that must be addressed before clinical translation.
Development of an ex vivo model for predicting in vivo tissue back pressure for subcutaneous injections.
Pang MJ, Hageman MJ, Lou H
Int J Pharm · 2026 Jul · PMID 42242514 · Publisher ↗
Tissue back pressure is an important indicator of tissue resistance during subcutaneous injection and is associated with injection performance and patient experience. Currently, assessments of tissue back pressure during...
Tissue back pressure is an important indicator of tissue resistance during subcutaneous injection and is associated with injection performance and patient experience. Currently, assessments of tissue back pressure during injection are mostly conducted in vivo, which are inconvenient, costly, and difficult to standardize. To overcome these limitations, this study used a pork belly-based model to develop an ex vivo-in vivo correlation (EVIVC) for tissue back pressure during injection. Subsequently, using the model developed, the effect of multiple factors on back pressure was evaluated, including (1) tissue-related factors: subcutaneous tissue thicknesses and pork belly freeze-thaw cycles; (2) injection operation-related factors: needle insertion angle; and (3) formulation- and device-related factors: formulation viscosity, temperature, osmolarity, and needle gauge. The mechanical properties of subcutaneous tissue were characterized using rheological and unconfined compression tests. As a result, an EVIVC was established, with a linear correlation between ex vivo and in vivo values (R = 0.87). Among all factors examined, formulation viscosity was the dominant determinant of tissue back pressure during injection, whereas subcutaneous tissue thickness, needle insertion angle, needle gauge, and formulation osmolarity had minimal influence. Also, freezing-thawing pork belly for three cycles had no significant effect on back pressure, supporting the appropriateness of storage conditions and the robustness of the model. The subcutaneous tissue thickness (< 2.5 cm vs. ≥ 2.5 cm) exhibited comparable viscoelastic behavior, but the normal-thickness tissue was more elastic. In summary, this ex vivo model can serve as a convenient, ethically preferable tool to reduce/replace in vivo studies for tissue back pressure assessment, potentially facilitating subcutaneous combination product development.
Quality-by-Design (QbD) optimization of lyophilization parameters for siRNA-loaded LNPs using sequential Design of Experiments (DoE).
Degey M, Meloni L, Dede B … +10 more , Guerreiro I, Penoy N, Sacré PY, Berger M, Conrard L, Hendrickx E, Maquoi E, Chain JL, Evrard B, Piel G
Int J Pharm · 2026 Jul · PMID 42235711 · Publisher ↗
Although lipid nanoparticles (LNPs) are widely used for RNA delivery, their use is limited by poor stability in liquid form during refrigerated storage. Lyophilization is a promising way to address this limitation. Howev...
Although lipid nanoparticles (LNPs) are widely used for RNA delivery, their use is limited by poor stability in liquid form during refrigerated storage. Lyophilization is a promising way to address this limitation. However, the relationship between cryoprotectant choice and process settings in determining LNP integrity after reconstitution is not yet fully understood. It also remains unclear whether conditions optimized for one formulation can be applied to others. Here, a Quality-by-Design (QbD) framework was used to optimize the lyophilization of siRNA-loaded LNPs using two sequential Design of Experiments (DoE). The main drivers of post-lyophilization LNP integrity were found to be cryoprotectant concentration and mode of addition, while freezing and primary-drying durations required fine tuning to balance physicochemical preservation and cake appearance. Under the selected condition, lyophilized CSL3/DSPE-PEG LNPs showed, after reconstitution, a Z-average size of 200 nm with a remaining low Polydispersity Index (PdI), maintained siRNA encapsulation efficiency (EE), preserved nanoscale organization, and maintained in vitro gene silencing efficiency. Compared with significant deviation from initial critical quality attributes (CQAs) within 13 days in the liquid state, lyophilization substantially extended stability at 4 °C and enabled preservation through 11 weeks at -30 °C. Applying the optimized process to LNPs with different lipid compositions showed that lyophilization-related size changes were mainly driven by the ionizable lipid, while the lipid-PEG anchor had only a minor effect. Overall, this study provides a QbD framework that links formulation composition to lyophilization outcomes and supports rational translation of the process across LNP formulations.
Hyaluronic acid-based microneedles: materials design, fabrication strategies, challenges, and solutions for biomedical applications.
Haq F, Kiran M, Aziz T … +3 more , Naeem W, Jamil MI, Qaisrani RN
Int J Pharm · 2026 Jul · PMID 42229835 · Publisher ↗
Hyaluronic acid (HA)-based microneedles have emerged as highly promising minimally invasive platforms for transdermal and transmucosal drug delivery, overcoming the limitations of conventional oral, topical, and injectab...
Hyaluronic acid (HA)-based microneedles have emerged as highly promising minimally invasive platforms for transdermal and transmucosal drug delivery, overcoming the limitations of conventional oral, topical, and injectable therapies. Owing to its excellent biocompatibility, biodegradability, hydrophilicity, non-immunogenicity, and intrinsic bioactivity, HA functions not only as a structural biomaterial but also as a therapeutic component that enhances tissue hydration, wound healing, immune modulation, and drug bioavailability. This review provides a comprehensive overview of the major fabrication strategies used for HA-based microneedles, including micro-molding, photolithography, centrifugal lithography, droplet-born air blowing, and additive manufacturing approaches. The effects of these techniques on microneedle geometry, mechanical strength, drug-loading capacity, dissolution behavior, and controlled-release performance are critically discussed. Recent biomedical applications of HA-based microneedles are systematically summarized, including transdermal drug delivery, vaccination and immunotherapy, diabetic and burn wound healing, oral ulcer treatment, allergy desensitization, alopecia areata therapy, ophthalmic delivery, and photodynamic therapy for oral leukoplakia. Particular emphasis is placed on multifunctional systems integrating nanoparticles, liposomes, antimicrobial agents, growth factors, antioxidants, and immunomodulatory compounds to achieve synergistic therapeutic effects. The review also highlights the mechanisms through which HA-mediated swelling, hydration, and biodegradation facilitate efficient and sustained drug release after microneedle insertion into biological tissues. Despite significant progress, challenges related to large-scale manufacturing, long-term stability, sterilization, dose reproducibility, and regulatory approval remain barriers to clinical translation. Overall, HA-based microneedles represent versatile next-generation platforms with strong potential for safe, effective, and patient-compliant biomedical applications.
Proximal policy optimisation based black-box optimizer for tailoring inhalation instructions of an inhaler for minimising mouth-throat deposition.
Ling Y, Lee A, Dong J … +2 more , Kourmatzis A, Cheng S
Int J Pharm · 2026 Jul · PMID 42229834 · Publisher ↗
Inhalation therapy using dry-powder inhalers (DPIs) offers targeted drug delivery for asthma and chronic obstructive pulmonary disease (COPD). Variation in deposition rate in the mouth-throat region depends on patient in...
Inhalation therapy using dry-powder inhalers (DPIs) offers targeted drug delivery for asthma and chronic obstructive pulmonary disease (COPD). Variation in deposition rate in the mouth-throat region depends on patient inhalation manoeuvres and techniques. The present study aimed to identify optimal combinations of head position, oral opening size, and mouthpiece insertion depth for three representative inhalation manoeuvres, corresponding to low, medium and high peak inspiratory flow rates (PIFRs). An idealised adult airway model was reconstructed and coupled with transient computational fluid dynamics (CFD) simulations that incorporated the Aerolizer® mouthpiece geometry, and inhaler resistance. A proximal policy optimisation (PPO) based black-box optimizer (BO) used deposition rate in mouth-throat (DE) as the reward signal to guide optimisation toward minimisation of mouth-throat deposition in the Alberta Idealised Throat (AIT) model. Key findings indicate that optimised technique adjustments can markedly reduce mouth-throat deposition. For the low PIFR case, total DE decreased from (28.82 ± 0.39) % in the original geometry to (5.11 ± 0.11) %. For the medium and high peak flow cases, average absolute reductions of 23.40 and 21.02 percentage points were achieved, respectively. Optimal actions across the three manoeuvres involved extending the head upward by 8.60-13.21, rotating left or right by 15.18-21.9, widening the oral opening to a three-finger width, and inserting the mouthpiece deeper by 7.99 mm-11.82 mm, based on the AIT model. These model-based findings suggest that head position and mouth-opening adjustments may influence aerosol transport and deposition patterns. The findings are hypothesis-generating and require validation in heterogeneous, subject-specific airway anatomies before clinical applicability can be inferred.
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