Int J Pharm [JOURNAL]
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200 papers
Innovative scaffold-based strategies for diabetic wound healing: progress and prospects.
Sathwara D, Maheshwari V, Patel H … +2 more , Dagli K, Joshi D
Int J Pharm · 2026 Jun · PMID 42140399 · Publisher ↗
Diabetic wounds present a major clinical concern due to chronic inflammation, impaired angiogenesis, excessive protease activity, and delayed extracellular matrix remodelling, leading to prolonged healing and high recurr...
Diabetic wounds present a major clinical concern due to chronic inflammation, impaired angiogenesis, excessive protease activity, and delayed extracellular matrix remodelling, leading to prolonged healing and high recurrence rates. Globally, over 536 million individuals were affected by diabetes in 2021, with diabetic foot ulcers impacting approximately 15-25% of these patients during their lifetime. Conventional wound dressings often fail to address the complex pathophysiology of diabetic wounds, necessitating advanced therapeutic strategies. Scaffold-based biomaterials have emerged as promising regenerative platforms by providing a 3-dimensional microenvironment that supports cell adhesion, proliferation, and controlled delivery of bioactive agents. Recent advances in nanofibrous scaffolds, hydrogels, and decellularized extracellular matrices have demonstrated enhanced angiogenesis, reduced inflammation, and accelerated wound closure in preclinical diabetic models, with several systems achieving over 90% wound contraction within a period of 14-21 days. This review critically discusses scaffold design principles, biomaterial selection, and emerging modification strategies, highlighting their translational potential for effective diabetic wound management.
Corrigendum to "An in-situ forming controlled release soft hydrogel-based C5a peptidase drug delivery system to treat psoriasis" [Int. J. Pharm. 671 (2025) 125244].
Patel P, Bhattacharjee P, Gedi V … +4 more , Duarte F, Tecza M, McGourty K, Hudson S
Int J Pharm · 2026 Jun · PMID 42140086 · Publisher ↗
Abstract loading — click title to view on PubMed.
Tolcapone-loaded nanostructured lipid carriers for improved oral delivery.
Pinto M, Machado CS, Costa S … +8 more , Díaz-Tomé V, Sarmento B, Otero-Espinar FJ, Remião F, de Monte-Vidal V, Cuello-Rodríguez S, Borges F, Fernandes C
Int J Pharm · 2026 Jun · PMID 42134709 · Publisher ↗
Tolcapone is a nitrocatechol-based drug used as adjuvant therapy in Parkinson's Disease (PD). Despite being effective in managing PD-associated symptoms, its use in the clinics is limited by its highly hepatotoxic profil...
Tolcapone is a nitrocatechol-based drug used as adjuvant therapy in Parkinson's Disease (PD). Despite being effective in managing PD-associated symptoms, its use in the clinics is limited by its highly hepatotoxic profile. Due to its low serum half-life and moderate oral bioavailability, frequent and high daily doses are necessary to obtain a significant therapeutic effect, which might enhance the risk of hepatotoxic events in patients. Hence, our study focuses on the development, characterization and early in vitro characterization of tolcapone-loaded nanostructured lipid carriers (NLCs) to improve tolcapone therapy. The newly designed NLCs, with sizes up to 120 nm, were prepared using the emulsion-solvent evaporation method with an entrapment efficiency (EE%) over 98%. Plus, NLCs were shown to be stable at different pHs and to have mucoadhesive properties. Cytotoxicity assays in HepG2 cells revealed that NLCs showed decreased cell viability, likely as a result of excessive intracellular lipid accumulation. Using Caco-2 and Caco-2/HT29-MTX co-culture models for permeability assays, the nanoformulations were capable of significantly transporting more tolcapone across the cell monolayers in comparison to free tolcapone without compromising cell monolayer integrity. Plus, the nanoformulations efficiently inhibited COMT in a cellular-based COMT inhibition assay using HepG2 cells. Early in vivo toxicological testing using Caenorhabditis elegans (C. elegans) demonstrated survival percentages > 88% after acute exposure to the nanoformulations in concentrations up to 100 µM. Together, the results obtained so far demonstrate that tolcapone-loaded NLCs have the potential to be a valid therapeutic option for the treatment of PD in the future.
Chloroquine-induced exosomal hybrid liposomes enable neutralization of endotoxins and exotoxins.
Wang Y, Su X, Xiao Y … +5 more , Sun C, Hu L, Gong J, Li G, Shen S
Int J Pharm · 2026 Jun · PMID 42134708 · Publisher ↗
Sepsis remains a major challenge in global clinical practice due to its persistently high mortality rate. Traditional antibiotics address symptoms rather than root causes, while the problem of drug resistance continues t...
Sepsis remains a major challenge in global clinical practice due to its persistently high mortality rate. Traditional antibiotics address symptoms rather than root causes, while the problem of drug resistance continues to escalate. Detoxification strategies such as monoclonal antibodies have shown limited efficacy in complex clinical settings, as their single-target specificity and narrow activity spectrum restrict their ability to neutralize diverse bacterial toxins. The therapeutic bottleneck lies in the absence of effective methods capable of simultaneously neutralizing Gram-negative bacterial endotoxins (such as LPS) and Gram-positive bacterial exotoxins (such as Hlα). To overcome this limitation, we drew inspiration from the natural "bait" mechanisms of living organisms to develop a biomimetic nanoscale detoxifier with broad-spectrum toxin adsorption and neutralization capacity. Specifically, chloroquine was used to inhibit autophagy lysosome formation in macrophages, promoting the release of exosomes enriched with toxin receptors CD14 and ADAM10. These exosomes (Exo) were then fused with artificial liposomes (Lip) possessing extensive membrane space to construct exosome membrane hybrid liposomes (Elip). Our results demonstrated that Elip effectively neutralized the hemolytic activity of Hlα and adsorbed LPS in vitro. In a subcutaneous HIα-induced local inflammation model, Elip completely prevented local skin and muscle tissue necrosis. In a systemic inflammation model induced by intravenous HIα, Elip significantly alleviated acute inflammatory damage in the lungs and liver, reducing key pro-inflammatory factor levels to near-normal ranges. In an LPS-induced shock model, all mice in the Elip treatment group survived. This study robustly confirmed that Elip successfully resolves the clinical challenge of simultaneously clearing endotoxins and exotoxins through a "synergistic detoxification" mechanism, offering a novel therapeutic strategy with significant translational potential that transcends traditional antibiotics for conquering sepsis.
Fabrication and biocompatibility evaluation of 3D printed tablets using Digital Light Processing (DLP) printing for the controlled release of ketoprofen.
Saropoulou E, Tzimtzimis E, Tzetzis D … +7 more , Panteris E, Spyros A, Vizirianakis IS, Ahmad Z, Cholevas C, Monou PK, Fatouros DG
Int J Pharm · 2026 Jun · PMID 42134707 · Publisher ↗
Digital Light Processing (DLP) is a widely utilized additive manufacturing (AM) technique in pharmaceutical research that operates via photopolymerization. This technology enables the fabrication of advanced drug deliver...
Digital Light Processing (DLP) is a widely utilized additive manufacturing (AM) technique in pharmaceutical research that operates via photopolymerization. This technology enables the fabrication of advanced drug delivery systems through the use of novel polymeric materials that can be precisely tailored to meet the requirements of specific dosage forms. In the present study, three-dimensional (3D) printed tablets were developed to achieve controlled release of the non-steroidal anti-inflammatory drug ketoprofen (Keto). Comprehensive physicochemical characterization, including thermal analysis, Fourier Transform Infrared (FTIR) spectroscopy, and Nuclear Magnetic Resonance (NMR) spectroscopy, confirmed the successful incorporation of the active pharmaceutical ingredient (API) within the polymer matrix and demonstrated its chemical stability following the photopolymerization process. In vitro drug release studies revealed controlled release profiles of Keto from the printed formulations, with the overall extent of drug release remaining limited to less than 20% after 24 h, highlighting the important aspect the important role of the starting materials (polymers) that requires further optimization. Morphological evaluation using optical microscopy and scanning electron microscopy (SEM) demonstrated uniform tablet geometry and smooth surface characteristics. Biocompatibility studies conducted using Caco-2 cells indicated that the formulations were non-toxic and suitable for oral administration. Furthermore, confocal laser scanning microscopy (CLSM) analysis showed preserved cellular morphology and membrane integrity after exposure to the formulations. These findings underscore the potential of photopolymerization-based 3D printing technologies as a versatile and effective platform for the fabrication of biocompatible solid drug delivery systems with customizable drug release behavior.
Exploring electroporation for miRNA mimic delivery into cells with milk-derived extracellular vesicles.
Ou H, Csuth TI, Molnár A … +2 more , Czompoly T, Kvell K
Int J Pharm · 2026 Jun · PMID 42128099 · Publisher ↗
Milk-derived extracellular vesicles (MEVs) are widely recognized as promising natural nanocarriers for drug delivery. However, current drug-loading strategies predominantly rely on electroporation, which is often associa...
Milk-derived extracellular vesicles (MEVs) are widely recognized as promising natural nanocarriers for drug delivery. However, current drug-loading strategies predominantly rely on electroporation, which is often associated with low and inconsistent loading efficiency. This study aims to address these limitations. We further incorporated the widely used miRNA-carrying liposome Lipofectamine RNAiMAX to assess whether combining MEVs with liposomal delivery could enhance performance while reducing Lipofectamine-associated cytotoxicity. The outcomes of integrating these two delivery strategies were examined, and the underlying mechanisms were explored. Combining Lipofectamine with electroporated MEVs markedly improved target cell viability compared with Lipofectamine alone, although this was accompanied by a substantial reduction in loading efficiency. Despite increased cell viability, apoptosis-related gene expression remained almost unchanged. Transmission electron microscopy and the absence of notable changes in protein content after electroporation suggest that reduced Lipofectamine transfection efficiency may result from excessive membrane stacking and encapsulation. We believe this phenomenon is caused by excessive electrostatic attraction between the two membrane components, and considering that miRNAs also carry a negative charge, this may hinder the loading process. Therefore, we neutralized the electroporated MEVs with calcium chloride and then allowed the miRNAs to be loaded via passive diffusion and membrane self-repair. We demonstrate a strategy that significantly enhances and stabilizes the loading efficiency of natural MEVs without introducing exogenous components that are difficult to eliminate and could potentially elicit immune responses. This study paves the way for the future use of natural MEVs as nanomedicine carriers with low cytotoxicity, low immunogenicity, and potential homing capabilities.
Rethinking freezing: the misconception of nucleation temperature and ice crystal formation in freeze-drying.
Kharatyan T, Gopireddy SR, Scherließ R … +1 more , Urbanetz NA
Int J Pharm · 2026 Jun · PMID 42128098 · Publisher ↗
The nucleation temperature is commonly believed to be a key factor influencing the pore size of lyophilised products. This assumption aligns with classical nucleation theory, which states that the nucleation rate, define...
The nucleation temperature is commonly believed to be a key factor influencing the pore size of lyophilised products. This assumption aligns with classical nucleation theory, which states that the nucleation rate, defined as the number of stable nuclei formed per unit time in a given volume, increases with the degree of supercooling, thereby producing more and smaller ice crystals in the frozen solution. During primary drying, these ice crystals sublimate, leaving behind pores that collectively form the microstructure of the lyophilisate. However, this interpretation does not fully consider a critical aspect of freezing: the exothermic nature of ice formation. This thermal event influences the resulting ice crystal structure, similar to how controlled temperature treatments, such as annealing, are purposefully used to modify ice crystal growth. To assess the impact of the temperature increase on ice crystal size distribution, a freeze-drying microscope was used in this study to compare rapidly frozen samples with those thermally treated under conditions present in a conventional freeze-dryer. The results indicate that the final ice crystal structure is not solely determined by the nucleation event, but is primarily governed by the duration of the temperature increase. However, a correlation was observed between nucleation temperature and the duration of the temperature rise, suggesting that nucleation temperature indirectly influences the freezing process. These findings challenge conventional assumptions regarding the role of nucleation temperature in freeze-drying and underscore the need for a revised perspective on ice crystal formation during freezing.
Liposomal design and shear shielding of colloidal matrices control drug release.
Dhakal N, Saw EE, Leong KLD … +4 more , Maw PD, Modh H, Kahouadji L, Wacker MG
Int J Pharm · 2026 Jun · PMID 42119862 · Publisher ↗
The drug release of liposomes is strongly modulated by mechanical stress, yet the interplay between carrier properties and the surrounding colloidal environment remains difficult to resolve experimentally due to the chal...
The drug release of liposomes is strongly modulated by mechanical stress, yet the interplay between carrier properties and the surrounding colloidal environment remains difficult to resolve experimentally due to the challenge of preserving shear conditions and carrier microenvironment during measurement. Here, we address this limitation using the Dispersion Releaser, a USP-referenced dialysis-based platform that enables in situ quantification of release under continuous shear. Computational fluid dynamics (CFD) simulations were used to map flow regimes across 25-100 rotations per minute (RPM), informing the selection of 25 RPM (low shear) and 75 RPM (high shear) for subsequent experiments. Two berberine-loaded liposomal formulations with distinct drug-dipalmitoylphosphatidylglycerol electrostatic interaction strengths showed significantly different release profiles under laminar flow, low-shear environment (f2 = 40.32) but converged under high shear (f2 = 68.31), and closely approached the permeation of free berberine, indicating that drug-membrane affinity governs release under mild shear but is overridden at higher mechanical stress. To investigate the role of the colloidal microenvironment, hydroxypropyl methylcellulose was introduced as an inert, non-permeable, shear-thinning matrix at concentrations of 1.5% and 2.5%. A dedicated permeation normalization separated the diffusional contribution of each matrix from carrier-mediated release. After normalization, the 2.5% matrix reduced cumulative release from ∼ 87% to ∼ 54% at 25 RPM, while the release modulation by the 1.5% was lost at 75 RPM. Notably, CFD revealed that both matrices suppressed turbulence despite wall shear stresses two to four orders of magnitude higher than in water, a finding incompatible with boundary-layer diffusion control, where a stagnant fluid layer adjacent to the vesicle surface limits mass transfer. Instead, the data support the proposed shear-shielding mechanism in which the colloidal matrix attenuates mechanical stress transmission to the vesicle. These results challenge the prevailing boundary-layer interpretation of colloid-mediated release retardation and highlight the need for shear-aware in vitro models in liposomal formulation design.
Dissolving microneedles with desferrioxamine-loaded TiCT MXene for rapid healing of microbial-infected wounds.
Yuan H, Yan C, Pan Q … +6 more , Chen K, Xie X, Zhang J, Wen C, Li Y, Zhang L
Int J Pharm · 2026 Jun · PMID 42119861 · Publisher ↗
The clinical translation of synergistic nanotherapies for deep skin infections is often hampered by a simple yet formidable obstacle: the skin barrier itself, which impedes adequate co-delivery of agents to the infection...
The clinical translation of synergistic nanotherapies for deep skin infections is often hampered by a simple yet formidable obstacle: the skin barrier itself, which impedes adequate co-delivery of agents to the infection site. To address this, we hypothesize that a transdermal microneedle (MN) delivery system can potentiate synergistic therapy by overcoming the skin barrier. We developed a dissolving MN patch co-loaded with deferoxamine (DFO)-anchored TiCT MXene nanosheets (DTM MNs) for the management of polymicrobial-infected wounds. The DTM MNs efficiently bypassed the stratum corneum, enabling deep intradermal delivery. Under near-infrared (NIR) irradiation, the MXene component exerted potent photothermal antibacterial effects against diverse pathogens (S. aureus, E. coli, MRSA, and C. albicans). Concurrently, the released DFO promoted angiogenesis and mitigated oxidative stress. Most importantly, through a direct comparative study with an equivalent-dose topical DTM solution, we mechanistically demonstrated that the MN-mediated delivery significantly enhanced the synergistic antibacterial and pro-angiogenic outcomes in vivo. Consequently, the DTM MN-treated wounds exhibited accelerated closure, reduced microbial burden, improved collagen deposition, and attenuated inflammation. Notably, the DTM MN treatment outperformed not only the vehicle control and solution group but also clinically used topical antimicrobial agents (erythromycin and fluconazole), highlighting its superior therapeutic profile. This work not only presents an effective wound dressing but, more fundamentally, validates the MN platform as a superior strategy for enhancing localized combination therapies by overcoming transdermal delivery barriers.
Novel Cu(II)-complex loaded Eudragit® nanoparticles: design, synthesis, characterization, and enhanced antitumor activity against triple-negative breast cancer.
Boztepe T, Sólimo A, de la Parra LSM … +9 more , Goldberg TJ, Figoli C, Bosch MA, Lamas DG, Huck-Iriart C, Gehring S, Islan GA, Callero M, León IE
Int J Pharm · 2026 Jun · PMID 42119860 · Publisher ↗
Breast cancer (BC) is the most frequently diagnosed malignancy in women and triple-negative breast cancer (TNBC) is its most aggressive subtype of BC, often associated with poor prognosis due to the limited current thera...
Breast cancer (BC) is the most frequently diagnosed malignancy in women and triple-negative breast cancer (TNBC) is its most aggressive subtype of BC, often associated with poor prognosis due to the limited current therapies. Effective delivery systems for metal-based drugs could improve antitumor efficacy and selectivity. In this study, the copper-complex [Cu(N-N-Fur)(NO)(HO)] (CuL1), which has demonstrated anticancer activity, was encapsulated into Eudragit®-based nanoparticles to enhance its effects against TNBC cell lines (MDA-MB-231, 4T1, and Hs 578T). Two nanosystems were prepared by nanoprecipitation followed by ultrasonication, using Eudragit® E100/S100 (ES-CuL1) or Eudragit® E100/NE100D (ENE-CuL1). The physicochemical and morphologic properties were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), fourier transformed infrared spectroscopy (FTIR), and small-angle X-ray scattering/wide-angle X-ray scattering (SAXS/WAXS). Both formulations showed encapsulation efficiencies of CuL1 above 90 % and in vitro controlled drug release over 72 h. Cytotoxicity and apoptosis were evaluated in 2D monolayers and 3D spheroids of TNBC. Notably, ES-CuL1 enhances the cytotoxic activity of CuL1, showing increased cytotoxicity across all 2D cell lines. Consistently, the encapsulated complex significantly reduced clonogenic survival from 0.5 µM onward and induced a higher proportion of late apoptotic cells in all tested lines. In 3D models, ES-CuL1 produced similar effects to the free drug in 4T1 spheroids but elicited a stronger cytotoxic response in Hs 578T spheroids, suggesting improved penetration and retention in tumor-like structures. The superior performance of ES-CuL1 supports its potential as effective nanocarrier for BC therapy and highlights the predictive value of 3D spheroids for nanodrug evaluation.
SedNet: A physics-informed operator-learning framework for rapid sedimentation velocity analytical ultracentrifugation analysis.
Basalla A, Kumar K, Cui Z … +1 more , Williams RO
Int J Pharm · 2026 Jun · PMID 42119681 · Publisher ↗
To date, analyzing data from sedimentation velocity analytical ultracentrifugation (SV-AUC) experiments has exclusively been performed using finite element method or other numerical solver-based techniques. These methods...
To date, analyzing data from sedimentation velocity analytical ultracentrifugation (SV-AUC) experiments has exclusively been performed using finite element method or other numerical solver-based techniques. These methods are slow, requiring repeated solving of the Lamm equation in order to obtain an accurate solution. In this paper, we demonstrate how the Lamm equation is alternatively solved accurately using machine learning's automatic differentiation by implementing it into the loss function of an inverse physics informed neural network (PINN). Subsequently, we confirm that by implementing the Lamm equation into a physics-informed deep operator network (PI-DeepONet), synthetic SV-AUC data can be easily generated and then inverted back into size distributions using a multi-layer perceptron (MLP). This combined PI-DeepONet and MLP creates an end-to-end framework, named SedNet, in which the Lamm equation is enforced via a physics-informed forward operator. We demonstrate how SedNet readily analyzes SV-AUC data and is generalized to real SV-AUC experimental data showing its potential applications as an analytical tool.
Legumain-responsive albumin-binding prodrug enables tumor-selective drug release and immunomodulatory remodeling for enhanced antitumor efficacy in ovarian cancer.
Chen H, Yue Z, Zhang Y … +6 more , Zhou Y, Su Y, Xu Y, Sun Y, Yu W, Shen Z
Int J Pharm · 2026 Jun · PMID 42114690 · Publisher ↗
BACKGROUND: Albumin-binding prodrugs represent a pharmacological strategy to improve systemic stability and tumor exposure of cytotoxic agents. Legumain, an asparagine endopeptidase selectively activated in the acidic tu...
BACKGROUND: Albumin-binding prodrugs represent a pharmacological strategy to improve systemic stability and tumor exposure of cytotoxic agents. Legumain, an asparagine endopeptidase selectively activated in the acidic tumor microenvironment, provides a mechanism for tumor-specific prodrug activation. In this study, we developed WC10-003, a legumain-responsive albumin-binding prodrug of belotecan, and investigated its pharmacological properties and antitumor activity in ovarian cancer models. METHODS: WC10-003 was synthesized by conjugating belotecan to a legumain-cleavable peptide linker. Albumin association, plasma stability, and enzymatic activation were evaluated to characterize its pharmacological behavior. Antitumor efficacy was assessed in ovarian cancer xenograft models and compared with irinotecan and belotecan. Transcriptomic analysis was performed to explore treatment-associated signaling alterations, and immunohistochemistry and flow cytometry were used to evaluate changes in tumor-associated macrophage polarization. RESULTS: Following intravenous administration, WC10-003 rapidly associated with endogenous albumin, forming a stable circulating complex that prolonged systemic exposure and enhanced tumor drug accumulation. In ovarian cancer xenograft models, WC10-003 produced significantly greater tumor growth inhibition than irinotecan or belotecan, consistent with improved pharmacokinetic and tumor exposure profiles. Transcriptomic profiling revealed suppression of PI3K-AKT-related signaling pathways associated with tumor growth. In addition, immunophenotypic analyses demonstrated a shift in tumor-associated macrophages toward a less immunosuppressive phenotype. Combination treatment with WC10-003 and anti-PD-1 antibody further enhanced antitumor efficacy, suggesting that pharmacologically optimized prodrug activation can sensitize tumors to immune checkpoint blockade. CONCLUSION: WC10-003 exhibits favorable pharmacological properties, including albumin-mediated stabilization and legumain-dependent tumor activation, resulting in enhanced antitumor efficacy in preclinical ovarian cancer models. These findings highlight a pharmacologically driven prodrug strategy for improving cytotoxic drug performance and support its further evaluation in combination with immunotherapy.
A bioengineered extracellular vesicle-based platform for targeted codelivery and multi-mechanistic therapy of skin fibrosis.
Fang Y, Hu C, Liu Y … +8 more , Wang L, Shen W, Sun B, Zhang Y, Zu R, Deng Y, Fang K, Xia H
Int J Pharm · 2026 Jun · PMID 42107749 · Publisher ↗
Systemic sclerosis (SSc) is an autoimmune fibrotic disease with limited effective therapies. Kaempferol (K) has promising antifibrotic activity but is limited by poor solubility and delivery efficiency. In this study, we...
Systemic sclerosis (SSc) is an autoimmune fibrotic disease with limited effective therapies. Kaempferol (K) has promising antifibrotic activity but is limited by poor solubility and delivery efficiency. In this study, we prepared kaempferol-loaded liposomes via the thin-film dispersion method, extracted exosomes by ultracentrifugation combined with PEG precipitation, and successfully constructed kaempferol-loaded liposome-exosome composite nanoparticle (KLE) through repeated freeze-thaw fusion.Characterization showed KLE had ideal physicochemical properties with an average particle size of 189.87 ± 12.62 nm, PDI of 0.40 ± 0.09, and encapsulation efficiency of 66.00 ± 3.07%. KLE exhibited sustained release behavior in vitro and enhanced DPPH radical scavenging capacity (55.92 ± 4.34% at 0.2 mg/mL) by activating the Nrf2/ARE antioxidant pathway. In a bleomycin-induced mouse model of localized scleroderma, topical administration of KLE significantly reduced dermal thickening, collagen deposition, and inhibited myofibroblast activation. It also downregulated TGF-β/Smad signaling, reduced pro-inflammatory factors, and regulated VEGF expression.This study demonstrates that KLE synergizes the high drug-loading capacity of liposomes and the delivery advantages of exosomes, serving as a safe and effective multi-target strategy for SSc-related skin fibrosis.
Development of AI-assisted 3D-printed degradable hydrogel microneedles for transdermal delivery of progesterone-loaded solid lipid nanoparticles: a novel approach to slowing Alzheimer's disease progression.
Suriyaamporn P, Wongprayoon P, Pannakkong W … +4 more , Pamornpathomkul B, Ngawhirunpat T, Rojanarata T, Opanasopit P
Int J Pharm · 2026 Jun · PMID 42107748 · Publisher ↗
Progesterone (PG) is used to slow the progression of neurodegenerative diseases, particularly Alzheimer's disease (AD) in postmenopausal women. However, PG exhibits high lipophilicity, resulting in strong binding to skin...
Progesterone (PG) is used to slow the progression of neurodegenerative diseases, particularly Alzheimer's disease (AD) in postmenopausal women. However, PG exhibits high lipophilicity, resulting in strong binding to skin tissues and plasma proteins, which may limit its systemic transport via transdermal routes. Solid lipid nanoparticles (SLNs) have been highlighted for their potential to enhance drug solubility and facilitate brain-targeted drug delivery for AD treatment. Microneedles (MNs) offer an advanced microtechnology for transdermal drug delivery, significantly improving drug permeation into the skin. However, traditional MNs fabrication methods face challenges related to shape control, dosage precision, high costs, and time consumption. Recent advancements in 3D printing technology offer a promising solution to these limitations. This study aimed to design and evaluate 3D-printed MNs-loaded with PG-SLNs for AD treatment. Biodegradable resin was utilized to fabricate MNs, aided by a Convolutional Neural Networks (CNNs) prediction model for improved accuracy. Mechanical strength, penetration efficiency, degradation, in vitro and in vivo drug delivery efficiency, cellular toxicity, and stability were evaluated. The optimized MNs, with a height of 756.98 ± 14.78 µm, effectively penetrated the skin barrier. SLNs exhibited a particle size of 308.91 ± 1.66 nm, PDI of 0.19 ± 0.08, and ZP of -30.03 ± 1.19 mV. The MNs retained sufficient mechanical strength post-drug loading, enabled efficient transdermal PG delivery, exhibited no cytotoxicity to neuronal cells, and remained physicochemically stable for up to 3 months. This study highlights the potential of 3D-printed MN patches as a novel transdermal drug delivery system, demonstrating practical feasibility for medical applications.
Corrigendum to "Dynamics of insertion and extraction of hollow pyramidal microneedles: experiments and numerical modelling" [Int. J. Pharm. 682 (2025) 125989].
Nadda R, Das DB, Yalcin TE … +3 more , Abraham AM, Larrañeta E, Donnelly RF
Int J Pharm · 2026 Jun · PMID 42107320 · Publisher ↗
Abstract loading — click title to view on PubMed.
Solvent-induced phase separation enhances the drug loading and encapsulation efficiency of a highly hydrophilic low-molecular-weight S-propargyl-cysteine in injectable PLGA microspheres.
Yin X, Chen B, Wang YQ … +5 more , Yan Y, Ding Q, Rinkiko S, Zhu YC, Zhu YZ
Int J Pharm · 2026 Jun · PMID 42105966 · Publisher ↗
Efficient encapsulating of highly hydrophilic low-molecular-weight compound within poly (D, L-lactic-co-glycolic acid) (PLGA) to obtain microspheres with both excellent drug loading capacity (DL) and encapsulation effici...
Efficient encapsulating of highly hydrophilic low-molecular-weight compound within poly (D, L-lactic-co-glycolic acid) (PLGA) to obtain microspheres with both excellent drug loading capacity (DL) and encapsulation efficiency (EE) was substantially challenging. This study specifically aimed to enhance both the DL and EE of this hydrophilic low-molecular-weight compound S-propargyl-cysteine (SPRC) while extending its release duration through implementation of the solvent-induced phase separation (SIPS) methodology. S-propargyl-cysteine (SPRC)-loaded PLGA microspheres (SP-MSs) were fabricated using conventional emulsion solvent evaporation techniques (W/O/W and S/O/W) and compared with those prepared via SIPS. The influences of various preparation techniques on critical pharmaceutical properties of sustained-release SP-MSs, including drug loading capacity, encapsulation efficiency, in vitro release profiles, surface-localized drug content, crystal state of SPRC, and microstructural characteristics were also systematically investigated. Microspheres sythesized through SIPS demonstrated a remarkable enhancement in DL, increasing from 0.90% to 9.91%, with the corresponding EE improving dramatically from 17.8% to 99.2%. Furthermore, the SIPS approach effectively mitigated the initial burst release phenomenon commonly observed in polymeric microsphere formulations. In vivo pharmacokinetic studies in Sprague-Dawley rats confirmed the sustained-release profile of the optimized formulation, maintaining stable plasma concentrations for an extended period of seven days. These findings establish SIPS as a superior methodology for encapsulating SPRC within PLGA microspheres, effectively addressing dual challenges of low DL and EE. This investigation provides significant methodological insights for the effective encapsulation of hydrophilic low-molecular-weight therapeutic agents within PLGA-based delivery systems, offering a promising strategy for achieving prolonged sustained-release both in vitro and in vivo.
Recent advances in novel drug carriers and advanced administration routes for inner ear drug delivery: challenges and future perspectives.
Wu H, Ding Y, Chen X
Int J Pharm · 2026 Jun · PMID 42105965 · Publisher ↗
Hearing loss (HL) affects over 1.5 billion people worldwide. The blood-labyrinth barrier (BLB) and the tympanic membrane (TM) can hinder the effectiveness of clinical treatments by preventing conventional drug delivery m...
Hearing loss (HL) affects over 1.5 billion people worldwide. The blood-labyrinth barrier (BLB) and the tympanic membrane (TM) can hinder the effectiveness of clinical treatments by preventing conventional drug delivery methods from precisely targeting the inner ear. This study aims to systematically summarise and analyse recent advances in novel drug carriers and delivery methods for inner ear drug delivery. This will provide theoretical support for the development of safe and effective HL treatment strategies. The review outlines the core characteristics of the latest invasive and non-invasive delivery routes and analyzes the design optimization points and in vivo and vitro application efficacy of novel nanocarriers, hydrogels, and gene carriers. The results suggest that non-invasive routes offer significant advantages in terms of safety and patient compliance, and that multifunctional novel carriers can substantially enhance drug accumulation levels within the inner ear. These approaches effectively protect cochlear hair cells and spiral ganglion neurons, thereby improving treatment outcomes for sensorineural hearing loss. However, critical challenges remain, such as the difficulty of regulating barriers and the imbalance between carrier performance and biocompatibility. Future efforts should therefore focus on precisely regulating the BLB and the TM, developing smart carriers and optimising clinical translation strategies. This will facilitate the efficient transition of inner ear drug delivery technologies from fundamental research to clinical application.
Multifunctional electrospun nanofibers for cancer therapy and regenerative reconstruction: current progress and future prospects.
Subhashchandra GK, Kanaujiya S, Kumar A … +5 more , Verma M, Arya DK, Pandey P, Mittal K, Rajinikanth PS
Int J Pharm · 2026 Jun · PMID 42105964 · Publisher ↗
Breast cancer continues to be the most commonly diagnosed cancer among women globally, and despite significant progress in standard treatment approaches, it is still associated with substantial recurrence rates and posto...
Breast cancer continues to be the most commonly diagnosed cancer among women globally, and despite significant progress in standard treatment approaches, it is still associated with substantial recurrence rates and postoperative complications. Systemic toxicity, drug resistance, poor tumor targeting, and compromised quality of life limit current treatment strategies, such as chemotherapy, radiotherapy, and surgery. In this context, multifunctional electrospun nanofibers have emerged as a promising platform for localized cancer therapy combined with regenerative reconstruction. This review comprehensively summarizes electrospun nanofiber-based systems for breast cancer management and associated biomedical applications. The fabrication techniques, including electrospinning, self-assembly, template synthesis, melt blowing, and centrifugal spinning, are critically discussed along with material selection using natural and synthetic polymers such as chitosan (CS), collagen, gelatin, poly(ε-caprolactone) (PCL), polylactic acid (PLA), and poly(lactic-co-glycolic acid) (PLGA). Special emphasis is placed on advanced nanofiber architectures, including core-shell, pH-responsive, and thermo-responsive systems, which enable controlled and site-specific drug release. Furthermore, the review highlights the role of nanofibers in localized chemotherapy, preventing postoperative recurrence, tissue regeneration, wound healing, cardiovascular repair, gene delivery, and tissue engineering. Recent in vitro and in vivo studies demonstrate that nanofiber-based drug delivery systems significantly enhance therapeutic efficacy while minimizing systemic toxicity. Despite encouraging outcomes, challenges related to large-scale production, mechanical stability, long-term safety, regulatory approval, and clinical translation remain. Future research should focus on scalable fabrication, multifunctional design optimization, and patient-specific therapeutic strategies. Overall, electrospun nanofibers represent a highly versatile and transformative platform for integrated breast cancer therapy and regenerative medicine.
Advanced nanomedicines to target prostate cancer cells: emerging molecular tools and future clinical prospects.
Abboud O, Sohail M
Int J Pharm · 2026 Jun · PMID 42105963 · Publisher ↗
Prostate cancer (PCa) has been considered the key cause of cancer deaths among men globally, especially in countries such as the Middle East and Asia. The percentage is disproportionately high in war-torn regions due to...
Prostate cancer (PCa) has been considered the key cause of cancer deaths among men globally, especially in countries such as the Middle East and Asia. The percentage is disproportionately high in war-torn regions due to healthcare challenges. Various factors contribute to the increase in the prevalence of this tumor, including lifestyle. Although many strategies have improved efficacy in the treatment field (e.g., androgen deprivation therapy (ADT), taxanes, and radium-223), nanomedicine remains the most effective drug-based method for targeting cancer cells. Most importantly, it provides a molecularly precise platform that integrates biomarker-guided targeting and multimodal treatment. Besides, this system integrates chemotherapy, gene silencing, photothermal therapy, and radiotherapy, which are redefining treatment paradigms. This work comprehensively reviews the key design principles of nanomedicine platforms and their potential for targeted prostate cancer therapy. Surface modification strategies, including polyethylene glycol (PEG) conjugation and PSMA ligand functionalization, enhance drug uptake and improve the precision of cancer cell targeting. Therefore, integrating nanomedicine-based delivery systems represents a promising strategy to improve the accuracy and therapeutic efficacy of prostate cancer treatment. Importantly, our study proposes next-generation precision methods, including AI-guided nanoparticle engineering, digital twin-based treatment prediction, and patient-derived organoid validation, to accelerate the clinical translation of advanced nanomedicines for prostate cancer.
A structured oral formulation database for machine learning: Uncovering data-informed design strategies to facilitate effective formulation development.
Zhou J, Li C, Zan P … +5 more , Wang Z, Wang B, Zhao Y, Gao X, Zheng A
Int J Pharm · 2026 Jun · PMID 42105962 · Publisher ↗
Oral dosage form development still relies heavily on empirical trial-and-error, while the high prevalence of poorly soluble drug candidates increases the need for structured data support. To address this limitation, we c...
Oral dosage form development still relies heavily on empirical trial-and-error, while the high prevalence of poorly soluble drug candidates increases the need for structured data support. To address this limitation, we constructed the Computational Pharmaceutics Intelligent Manufacturing Database (CPIMD), an ML-oriented database that integrates physicochemical properties of active pharmaceutical ingredients, qualitative excipient compositions, release categories, and in vitro dissolution data from 683 marketed oral dosage forms approved by the PMDA of Japan. A standardized workflow for data cleaning, feature encoding and dissolution profile digitalization was used to transform raw information into a machine learning ready dataset. Using CPIMD, we applied unsupervised clustering to characterize four major formulation pattern clusters defined by drug properties, release categories, and associated excipient combinations. Together, these clusters summarize a formulation pattern matrix linking API physicochemical properties, release objectives, and associated functional excipients within the current dataset. A proof-of-concept random forest model further showed that binary excipient features could predict release type with 97.1% test accuracy, supporting the utility of CPIMD for downstream ML applications. CPIMD provides a structured data foundation for predictive modeling, preliminary excipient screening, and data-informed oral formulation development.
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