Int J Pharm [JOURNAL]
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200 papers
Cyclodextrin platforms for siRNA delivery: turning design into new therapies.
Sonje DP, Wairkar S
Int J Pharm · 2026 Jun · PMID 42105961 · Publisher ↗
Small interfering RNA (siRNA) is a powerful tool for post-transcriptional gene silencing, with profound therapeutic implications across a spectrum of diseases, including cancer, hereditary disorders, metabolic disorders,...
Small interfering RNA (siRNA) is a powerful tool for post-transcriptional gene silencing, with profound therapeutic implications across a spectrum of diseases, including cancer, hereditary disorders, metabolic disorders, neurodegenerative disorders, and microbial infections. Despite extensive research on siRNA, its delivery remains a significant challenge due to its inherent instability, susceptibility to nuclease degradation, poor cellular uptake, and rapid renal clearance. Cyclodextrins (CDs), a family of cyclic oligosaccharides, have attracted significant attention as non-viral siRNA nanocarriers due to their unique physicochemical properties, such as a hydrophilic exterior, a hydrophobic cavity, biocompatibility, and the ability to form inclusion complexes with biomolecules. In this review, we explore the mechanism of CD-mediated siRNA delivery, emphasizing the design and functionalization of CD-based nanocarriers. Furthermore, CD-polyrotaxanes (PRs) and polymer-conjugated CDs provide enhanced stability and controlled siRNA release, while targeting ligand modifications improve systemic circulation and specificity. Herein, co-delivery of siRNA with therapeutics using CD-based carriers showed synergistic effects that enhance gene silencing and therapeutic efficacy. Moreover, innovative strategies, such as pH-responsive, enzyme-activated, and redox-sensitive CD-based systems, are being developed to improve siRNA bioavailability and intracellular trafficking. Finally, we consider the translational potential of these platforms, identifying key challenges and future perspectives that will shape the next generation of CD-based siRNA therapies.
From stiffness-softness paradox to drug delivery systems: mechanical properties and regulation in tumor progression.
Zhu W, Wang C, Sun M … +1 more , Tao J
Int J Pharm · 2026 Jun · PMID 42105960 · Publisher ↗
Tumor progression is regulated by unique mechanical properties. However, there is a "stiffness-softness paradox" between tumor tissues and tumor cells in terms of mechanical characteristics. On the one hand, abnormal sti...
Tumor progression is regulated by unique mechanical properties. However, there is a "stiffness-softness paradox" between tumor tissues and tumor cells in terms of mechanical characteristics. On the one hand, abnormal stiffening of tumor tissue promotes tumor proliferation and invasion by activating mechanical related signaling pathways, promoting epithelial mesenchymal transition (EMT), affecting angiogenesis, and aggravating the immunosuppressive microenvironment; On the other hand, tumor cells themselves undergo softening, which enhances their deformability through cytoskeletal reorganization. This adaptive softening assists tumor cells escape from the primary site and transform into circulating tumor cells (CTCs). These CTCs then support their own survival in the circulatory system by forming CTC clusters, intracellular bacterial associations, or metabolic adaptations, thereby promoting distant metastasis. These mechanical characteristics of tumors are inspiring novel anti-cancer strategies aimed at targeting and normalizing mechanical abnormalities in solid tumor tissues and cells, particularly in the field of intelligent drug delivery systems (DDS). With the advantages of modifiability, targeting and controlled release, DDS offers promising approaches for modulating tumor mechanical properties. This article focuses on the distinctive mechanical characteristics of tumor tissues and cells, systematically reviews the roles of tumor tissue and tumor cell mechanical abnormalities in tumor progression, and summarizes recent advances in mechanical regulation strategies based on DDS for cancer treatment, as well as the intrinsic mechanical regulation of DDS and external mechanical triggering of drug release. Additionally, mechanical modulation methods beyond nanomedicine are discussed, providing potential directions for developing novel nano‑therapeutic strategies for mechanical regulation.
Harnessing exosomes for advanced drug delivery in cancer theranostics.
Dhanawat M, Garima, Wilson K … +6 more , Bhushan B, Vohra V, Nair AK, Chaubey P, Mittal N, Girdhar J
Int J Pharm · 2026 Jun · PMID 42105959 · Publisher ↗
Exosomes are nanoscale extracellular vesicles released by various cell types and have gained significant attention for their ability to transport diverse bioactive molecules. Their inherent stability, tumor-targeting cap...
Exosomes are nanoscale extracellular vesicles released by various cell types and have gained significant attention for their ability to transport diverse bioactive molecules. Their inherent stability, tumor-targeting capability, biocompatibility, and low immunogenicity make them promising candidates for drug delivery in cancer therapy. Despite these advantages, a gap remains between their biological understanding and optimal clinical application. Exosomes play a dual role in cancer as both therapeutic delivery systems and mediators of disease progression. Their phospholipid membrane enhances targeted drug delivery, while exosome-associated biomarkers offer new opportunities for cancer diagnosis. This review provides a comprehensive overview of exosome biogenesis, isolation methods, cargo loading strategies, roles in cancer progression, and applications in drug delivery and theranostics. It also highlights the advantages, limitations, and current clinical advancements of exosome-based systems. Overall, exosomes represent a cutting-edge platform with the potential to transform future cancer diagnosis and treatment.
Oleoyl-hyaluronate nanoparticles for enhanced stability and bioactivity of encapsulated coenzyme Q10.
Juhaščik M, Moravcová M, Čožíková D … +7 more , Polášková J, Sita J, Kulhánek J, Dolečková I, Sedláčková J, Židek O, Ondreáš F
Int J Pharm · 2026 Jun · PMID 42105958 · Publisher ↗
This study presents the successful encapsulation of coenzyme Q10 (CoQ10) within sodium oleoyl hyaluronate (O-HA; Mw ∼12,000 Da) nanoparticles, creating a concentrated, liquid colloidal dispersion. The nanoprecipitation p...
This study presents the successful encapsulation of coenzyme Q10 (CoQ10) within sodium oleoyl hyaluronate (O-HA; Mw ∼12,000 Da) nanoparticles, creating a concentrated, liquid colloidal dispersion. The nanoprecipitation process achieved high encapsulation efficiency (up to 96%) and a loading capacity of 2.4-3.0 mg·mL. The physicochemical properties of these solid polymeric nanoparticles, including particle size (240-295 nm) and negative zeta potential (-50 to -53 mV), were optimized to ensure colloidal stability. Long-term stability assessments demonstrated unusual CoQ10 retention and colloidal integrity within this liquid system. The nanoparticles exhibited 90% chemical retention after six months at 40 °C, and maintained their initial particle size (∼273 nm) and zeta potential (∼-53 mV), with 92% chemical retention after one year and 83% after two years at 25 °C. Biological studies revealed that O-HAQ10 nanoparticles enhanced bioactivity, providing protection against reactive oxygen species and exerting anti-inflammatory effects (upregulation of HMOX1, downregulation of IL-6) at cellular exposure concentrations of 4-40 µg·mL. Increased expression of collagen types IV and VII suggested a role in reducing signs of aging. Due to CoQ10's extreme lipophilicity and high molecular weight, its effective partitioning into viable skin layers is severely restricted. Therefore, to facilitate dermal delivery, the aqueous nanoparticle dispersion was incorporated into a ∼40:60 water-in-oil (W/O) emulsion using sorbitan olivate as a non-ionic emulsifier. In vitro penetration studies demonstrated that W/O emulsion significantly enhanced skin absorption by 3.8-fold compared to unencapsulated CoQ10 and commercial liposomal formulations. These findings establish O-HAQ10 nanoparticles as a promising, stable delivery system for dermatological applications.
Smart exosomes: multimodal engineering strategies for logic-gated and stimuli-responsive precision theranostics.
Hu Y, Yang X, Shu F … +4 more , Jin L, Sarsaiya S, Han S, Chen J
Int J Pharm · 2026 Jun · PMID 42105957 · Publisher ↗
Exosomes are endogenous extracellular vesicles with exceptional biocompatibility and intrinsic targeting potential, yet their clinical translation is limited by functional heterogeneity, insufficient controllability, and...
Exosomes are endogenous extracellular vesicles with exceptional biocompatibility and intrinsic targeting potential, yet their clinical translation is limited by functional heterogeneity, insufficient controllability, and lack of spatiotemporal precision. While numerous engineering strategies have been developed, most remain confined to single-function enhancement and fail to achieve coordinated, programmable therapeutic control. In this Review, we propose the concept of "smart exosomes" as a next-generation paradigm for exosome engineering, defined by multi-stimuli responsiveness, Boolean logic-gated signal processing, and multimodal theranostic integration. We summarize exosomal biomarkers across animal-, plant-, and microbial-derived vesicles and highlight their evolving roles from passive identifiers to active structural and functional interfaces for intelligent design. Natural exosome organotropism and surface molecular fingerprints are discussed as a biological foundation for precision targeting. We further review the major exosome engineering strategies, including genetic modification, chemical conjugation, physical manipulation, and exosome-nanocarrier hybridization, which together constitute a versatile engineering toolbox. A central focus is the integration of endogenous and exogenous cues-such as pH, redox status, enzymatic activity, and external physical stimuli-into logic-gated exosome systems capable of multi-input sensing and conditional activation. Importantly, we explicitly differentiate experimentally validated logic-gated exosome systems from hypothetical or extrapolated designs, and we discuss the key technological barriers to achieving true multi-input Boolean logic execution in vivo. Such designs enable programmable cargo release, imaging feedback, and precisely controlled therapeutic action. Finally, we discuss key translational challenges and outline future directions toward AI-assisted design, plant-derived exosome platforms, and cooperative multi-stimulus response systems. Collectively, this Review establishes a conceptual framework for programmable exosome-based precision theranostics.
Ionic liquids as synergistic stabilizers in biopharmaceuticals: controlling protein aggregation in formulation and processing.
Khan L, Tathe U, Dandekar P … +1 more , Jain R
Int J Pharm · 2026 Jun · PMID 42105956 · Publisher ↗
Ionic liquids (ILs) have emerged as a versatile class of tunable additives with growing relevance in the stabilization and processing of monoclonal antibodies (mAbs) and other therapeutic proteins. This review critically...
Ionic liquids (ILs) have emerged as a versatile class of tunable additives with growing relevance in the stabilization and processing of monoclonal antibodies (mAbs) and other therapeutic proteins. This review critically examines the application of ILs, with particular emphasis on imidazolium and choline-based systems, as synergistic additives and co-excipients for mitigating protein aggregation and enhancing stability across biopharmaceutical manufacturing workflows. Unlike previous broad reviews of ionic liquids in pharmaceutical applications, this review specifically focuses on their role as stabilizing co-excipients for therapeutic proteins and critically examines their translational relevance through comparative, regulatory, and safety-oriented perspectives across the biopharmaceutical manufacturing continuum. Rather than positioning ILs as replacements for conventional excipients, this manuscript highlights their integration into the existing formulation buffers, downstream purification steps, and alternative separation platforms to improve product robustness, recovery, and shelf life. Application-driven case studies have been discussed to illustrate the stabilizing and process-enabling roles of ILs, including the use of 2-methyl imidazolium dihydrogen phosphate in antibody formulation and protein A chromatography, choline-based ILs in high-concentration antibody stabilization, and IL-assisted aqueous biphasic and micellar systems for antibody isolation and purification. Mechanistic insights into ion-protein interactions, hydration-shell modulation, and concentration-dependent effects have been discussed alongside structure-toxicity relationships to contextualize performance within biological and regulatory constraints. In addition, the review addresses critical considerations related to biocompatibility, cytotoxicity, scalability, and regulatory acceptance, emphasizing the importance of rational IL design and application-specific safety assessment. Collectively, this work provides an integrated framework correlating stabilization mechanisms, comparative formulation performance, translational safety considerations, and regulatory perspectives of ILs, positioning them as multifunctional co-excipients that may strengthen existing biopharmaceutical formulation and processing strategies while guiding future research toward safe and effective industrial translation.
Immune cell-targeted nanocarrier delivery systems for inflammatory bowel disease therapy: mechanisms and strategies.
Tang Y, Wu Z, Zhao H … +10 more , Liang W, Qu A, Wang R, Gao S, Zhao P, Liu J, Zhang Z, Han X, Liang W, Zhang W
Int J Pharm · 2026 Jun · PMID 42105955 · Publisher ↗
Inflammatory bowel disease (IBD) is a chronic intestinal disorder caused by immune dysregulation, leading to persistent inflammation and recruiting a large number of immune cells to the intestinal inflammation sites. Whe...
Inflammatory bowel disease (IBD) is a chronic intestinal disorder caused by immune dysregulation, leading to persistent inflammation and recruiting a large number of immune cells to the intestinal inflammation sites. When immune cells become aberrantly activated, macrophages, neutrophils, dendritic cells, T cells and B cells infiltrate affected intestinal sites, releasing pro-inflammatory cytokines that amplify tissue damage and perpetuate disease progression. Base on pathological mechanisms, immune cell-targeted nanocarrier systems have emerged as innovative platforms for precise drug delivery to inflamed colonic regions, minimizing off-target effects, regulating immune imbalance and enhancing therapeutic efficacy. This review systematically examines the roles of key immune cells and their associated signaling pathways in IBD pathogenesis, with a particular focus on immune regulatory mechanisms at inflammatory foci. Furthermore, it explores design strategies for nanoparticles functionalized with specific ligands, including mannose, folic acid, lactoferrin, and hyaluronic acid, which facilitate selective targeting of immune cells. These modifications optimize immune cell phenotype modulation, cytokine secretion control, and tissue repair, significantly reducing systemic toxicity and improving drug bioavailability. Finally, challenges and future perspectives, including ligand specificity optimization, clinical translation barriers, and multifunctional nanoparticle development, are discussed to advance IBD treatment paradigms. Collectively, this comprehensive summary of immune cell-targeted nanotherapeutics provides novel insights into precision treatment strategies for IBD, paving the way for more effective and targeted therapeutic interventions.
Effective process for screening melanin binding affinity of small molecule drugs and new drug candidates.
Vanhanen P, Reinisalo M, Lajunen T … +3 more , Kalinin S, Leskinen J, Urtti A
Int J Pharm · 2026 Jun · PMID 42103108 · Publisher ↗
Melanin binding of small molecule drugs can lead to targeted disposition to the pigmented tissues and prolonged pharmacological responses in the eye. Melanin binding of drugs in vitro correlates with in vivo binding, but...
Melanin binding of small molecule drugs can lead to targeted disposition to the pigmented tissues and prolonged pharmacological responses in the eye. Melanin binding of drugs in vitro correlates with in vivo binding, but current workflows for binding affinity require multiple slow steps, and analytical method development, and/or they may result in high data variability. We developed tangential flow filtration-based methodology to produce size-specific fractions of water-soluble melanin nanoparticles (MNPs), reducing production time from 2-3 days to just a few hours and yielding MNPs with enhanced fluorescence signal. Improved MNPs enabled modifications to a previously published microscale thermophoresis-based melanin binding protocol, shifting analytical focus toward thermophoretic behavior, reducing data variability, and improving reproducibility. The process was tested with nine compounds with varying melanin binding affinities, and the results were consistent with literature, confirming the ability of the method to differentiate compounds based on melanin binding. Fast and reliable workflow will be useful in screening binding affinity for therapeutics and new drug candidates to melanin thereby facilitating ocular drug discovery and construction of predictive pharmacokinetic simulation models.
Nano-in-micro dry powder formulations combining azithromycin and menadione as adjuvant against pulmonary P. aeruginosa infections.
Shehu K, Osti J, Hittinger M … +2 more , Kraegeloh A, Schneider M
Int J Pharm · 2026 Jun · PMID 42097470 · Publisher ↗
Chronic lung infections caused by Pseudomonas aeruginosa are a major contributor to morbidity and mortality in patients with cystic fibrosis. Biofilm formation and the emergence of antibiotic resistance limit the effecti...
Chronic lung infections caused by Pseudomonas aeruginosa are a major contributor to morbidity and mortality in patients with cystic fibrosis. Biofilm formation and the emergence of antibiotic resistance limit the effectiveness of current inhaled therapies, highlighting the need for innovative formulation strategies that enhance local antibacterial efficacy while preserving epithelial integrity. This study explores a nano-in-micro inhalable formulation design that combines azithromycin (AZM) with the antibiotic adjuvant menadione (MEN) to enhance antibiofilm activity under biorelevant pulmonary exposure conditions. Nano-embedded microparticles (NEMs) were developed as an inhalable "Trojan particle" approach, combining AZM in a microparticle matrix with MEN-loaded polymeric nanoparticles. The formulations were produced by spray drying and characterized in terms of morphology, aerodynamic performance, solid-state properties and redispersibility. Antibiofilm activity against P. aeruginosa biofilms and epithelial safety in Calu-3 cells were evaluated using biorelevant aerosol exposure models, including nebulization and dry powder atomization. NEMs exhibited favorable aerodynamic properties suitable for bronchial delivery. Incorporation of MEN into the NEM system enhanced the antibiofilm efficacy of AZM compared with the microparticle matrix-only formulation, indicating that the adjuvant effect of MEN was retained upon translation into an inhalable formulation. Cytotoxicity studies demonstrated that neither nebulized nor dry powder-delivered formulations compromised the membrane integrity of Calu-3 cells. These results indicate that the combination of azithromycin and menadione within a NEM design preserves drug activity and adjuvant efficacy while enabling effective aerosol delivery. Future studies in more complex and disease-relevant models will further strengthen the understanding of the translational potential of this approach.
API particle size governs in situ forming implant formation, microstructure evolution and performance.
Roy M, Wang X, Hao Z … +6 more , Wang R, Wang Y, Qin B, Li Q, Zhang Q, Burgess DJ
Int J Pharm · 2026 Jun · PMID 42097469 · Publisher ↗
In situ forming implants (ISFIs) are long-acting injectable (LAI) drug delivery systems that undergo phase inversion upon contacting an aqueous environment, resulting in the formation of a semisolid-solid implant. To dat...
In situ forming implants (ISFIs) are long-acting injectable (LAI) drug delivery systems that undergo phase inversion upon contacting an aqueous environment, resulting in the formation of a semisolid-solid implant. To date, six ISFI products are commercially available, four of which are suspension-based formulations. Despite their growing clinical use, no generic ISFI products have reached the market. This underscores the need to better understand their complex behavior and to elucidate the critical quality attributes (CQAs) that govern their performance. While relationships between polymer physicochemical properties (e.g., molecular weight, lactic-to-glycolic acid ratio, end-group chemistry) and release kinetics have been extensively explored, the influence of the active pharmaceutical ingredient (API) remains insufficiently defined. To fill this knowledge gap, the present study investigates a risperidone ISFI that is qualitatively and quantitatively (Q1/Q2) equivalent to the commercial product Perseris®. Previous work has shown that Q1/Q2 equivalence alone does not ensure equivalent performance in vitro and in vivo, prompting the need to investigate additional formulation attributes. The current work focuses on evaluating the impact of API particle size and morphology on implant formation and in vitro release behavior. Thus, formulations containing risperidone with different particle sizes were prepared and evaluated. Subsequently, implant microstructure, water uptake, polymer degradation, and drug release were extensively characterized. A novel aspect of this work is the application of multiple imaging strategies, including laser scanning confocal microscopy (LSCM) for surface imaging and an adhesive thin-film technique for internal imaging, enabling detailed investigation of the evolution of microstructural differences between formulations. The findings highlight the importance of API particle size in governing implant microstructure, water uptake, polymer degradation, and in vitro release behavior, providing insight that will support the development of future generic and innovator ISFI products.
Design and formulation strategies to modulate drug release from implantable devices.
Magill ER, Adhami M, Fandiño OE … +3 more , Lu Y, Domínguez-Robles J, Larrañeta E
Int J Pharm · 2026 Jun · PMID 42092648 · Publisher ↗
Implantable drug delivery systems (IDDSs) provide an attractive alternative for delivering drugs locally or systemically in a sustained manner. They offer a promising therapeutic option for patients with chronic conditio...
Implantable drug delivery systems (IDDSs) provide an attractive alternative for delivering drugs locally or systemically in a sustained manner. They offer a promising therapeutic option for patients with chronic conditions that traditionally rely on continuous drug administration via oral or injectable routes. Achieving these benefits, however, depends critically on the selection of materials and excipients used in the preparation of IDDSs. This review focuses on preformed solid IDDSs and how their design and formulation strategies can be adapted to optimise drug release. A wide range of aspects, such as implant design and formulation strategies, are explored. The review provides a comprehensive discussion of conventional formulation approaches adapted for IDDSs, including solubility enhancement, polymer degradation, porosity modulation, particle size reduction, and the incorporation of micro- or nano-encapsulation strategies. In addition, design parameters such as implant geometry and the use of rate-controlling membranes are discussed in detail. The article emphasises the importance of integrating advances in disciplines such as polymer science, manufacturing technologies, and drug formulation into the design of preformed IDDSs. Future directions emphasise personalised implant design, smart materials, and multi-drug delivery systems to address evolving clinical needs.
Nanocarrier and probe strategies for nuclear targeting.
Inel M, Yildirim A, Ozturk B … +1 more , Yilmaz M
Int J Pharm · 2026 Jun · PMID 42092647 · Publisher ↗
Nuclear targeting probes and nanocarriers remain limited in the literature, highlighting a critical gap in subcellular targeting strategies. This review outlines four key strategies for delivering probes and drugs to the...
Nuclear targeting probes and nanocarriers remain limited in the literature, highlighting a critical gap in subcellular targeting strategies. This review outlines four key strategies for delivering probes and drugs to the cell nucleus. Active targeting with peptides, aptamers, and proteins enables precise nuclear import and supports real-time mapping of epigenetic activity. Cationic molecules bind DNA via charge-based and structural compatibility, while nanoparticle size is tuned to bypass nuclear pores after tumor accumulation. Nuclease-resistant, peptide-conjugated, and light-responsive carriers improve nuclear delivery by avoiding degradation and lysosomal trapping. Lipid-based and aptamer-guided systems bring therapeutics close to genomic DNA, with stimuli like acidity or light enabling controlled release. Carbon and gold nanostructures showcase how these strategies improve nuclear access and therapeutic impact. Overall, effective designs align delivery methods with biological barriers and quantify nuclear targeting efficiency, advancing nucleus-focused diagnostics and treatments.
Amino acid derivatives and surfactants as multifunctional excipients for overcoming drug solubility and permeability challenges.
Surabhi KS, Anegundha S, Sridhar BK
Int J Pharm · 2026 Jun · PMID 42092646 · Publisher ↗
Amino acid derivatives and surfactants are gaining increased application in formulation design due to their unique properties such as biocompatibility and ability to form molecular interactions. This review delves into t...
Amino acid derivatives and surfactants are gaining increased application in formulation design due to their unique properties such as biocompatibility and ability to form molecular interactions. This review delves into the emerging role of amino acid derivatives for overcoming drug solubility and permeability challenges, assessing their mechanisms and potential in formulation design. Drug solubility is enhanced by amino acid derivatives and surfactants through several mechanisms such as micelle formation, ion pairing, and hydrotropy, while the transcellular uptake, transporter activation, and prodrug formation enhance permeability. The article summarizes the scope of Gemini amino acid-based surfactants (AAGSs), which have lower critical micelle concentration (CMC), higher solubilization, strong surface activity, better bioavailability and improved stability due to their advanced dimeric amphiphilic features. Beyond solubility and permeability enhancement, future research may aim at optimizing amino acid derivatives for targeted delivery, exploring synergistic effects with nanotechnology, including smart surfactants, nanocarrier systems and targeting neurodegenerative diseases. Overall, amino acid-based systems offer a promising platform for circumventing bioavailability limitations.
Predicting plasma concentration-time profiles of orally disintegrating tablets with delayed absorption under fed conditions without water.
Oyabu Y, Takagi T, Yamashita S … +1 more , Yamashita F
Int J Pharm · 2026 Jun · PMID 42082063 · Publisher ↗
Orally disintegrating tablets (ODTs) offer substantial advantages for patients with swallowing difficulties; however, under fed conditions without water, ODTs frequently exhibit delayed absorption, complicating pharmacok...
Orally disintegrating tablets (ODTs) offer substantial advantages for patients with swallowing difficulties; however, under fed conditions without water, ODTs frequently exhibit delayed absorption, complicating pharmacokinetic evaluation and Bioequivalence (BE) assessment. In particular, unpredictable prolongation of T necessitates excessively dense and prolonged blood sampling in BE studies, increasing ethical and economic burdens on study participants and sponsors. To address this challenge, we developed a novel framework to predict plasma concentration-time profiles with delayed absorption under this dosing condition. Absorption-delay functions were derived from published individual plasma concentration-time profiles of rivaroxaban ODTs using a numerically stable, matrix-based non-negative least-squares deconvolution method. These functions were applied by convolution to simulate without-water plasma concentration-time profiles using the corresponding individual-level with-water profiles. In addition, to overcome the limited availability of individual-level data, we developed a Gaussian process-based generative model that reconstructs realistic individual profiles using only reported means and standard deviations of plasma concentration data. The proposed framework accurately reproduced observed profiles of multiple rivaroxaban ODT formulations and demonstrated transferability to ODTs containing different active ingredients, including tolvaptan and sildenafil. Predicted T and C values were consistent with reported data. This framework provides a practical and quantitatively grounded basis for predicting delayed absorption of ODTs administered under fed conditions without water and for the rational design of sampling schedules in BE studies, enabling more effective, cost-efficient, and patient-friendly study designs.
Development of UV-cured captopril-loaded ink for pharmaceutical 3D printing by custom-built SSE extruder.
Kozakiewicz-Latała M, Krzaczkowski P, Śnietura W … +5 more , Brożyna J, Czapor-Irzabek H, Brożyna M, Malec K, Karolewicz B
Int J Pharm · 2026 Jun · PMID 42082062 · Publisher ↗
It is widely acknowledged that conventional dosage forms are frequently not adequately customized to meet the specific clinical requirements of individual patients, what induces the need to process existing dosage forms...
It is widely acknowledged that conventional dosage forms are frequently not adequately customized to meet the specific clinical requirements of individual patients, what induces the need to process existing dosage forms to improve comfort and patient compliance. This phenomenon is especially evident in pediatric and geriatric populations, where there is a shortage of adequate doses of medication or where a difficulty is reported in their administration. Personalized soft gel-based dosage forms offer a viable solution to the problems associated with the administration of solid forms, especially in special needs populations. One of the most promising technologies that has the potential to facilitate personalization and the production of soft dosage forms is three-dimensional printing (3DP) using the semi-solid extrusion (SSE) method. This method allows the processing of low melting point materials and colloidal materials, e.g. gels and pastes. In this study, a light-curable gel (ink) was designed using a polyethylene glycol diacrylate (PEGDA) as a base polymer. Riboflavin and L-arginine were used as photoinitiators, demonstrating that it is possible to fabricate UV-cured gels without the need for potentially toxic ingredients such as triethylamine, or TPO/DPPO commonly used in this type of formulations. The model drug incorporated into the ink was captopril, which primary indication is the treatment of hypertension and heart failure. The possibility of using an individualized approach to its dosing could reduce the risk of adverse effects, particularly in elderly or pediatric patients. For the 3D printing process of soft dosage forms SSE extruder designed by the authors has been used. Demonstrative version of extruder can be installed in commercial FDM (Fused Deposition Modeling) printers which enables the execution of a considerable number of experiments using a variety of gels under controlled laboratory conditions, without the need for a significant financial investment. In a final experiment, a series of donut-shaped tablets were printed from the designed ink, which exhibited immediate drug release (over 80% within 30 min). Additionally, in this study an interesting phenomenon observed was improvement in polymerization of API-incorporated ink, what based on NMR spectra analysis may be explained by beneficial influence of captopril structure itself and its thiol group on cross-linking process progress. Summarizing, an ink composition formulated in the presented project that contains non-toxic photoinitiators and co-initiators can be utilized in an innovative self-assemble SSE extruder compatible with FDM commercial 3D printer, with optional UV-curing system.
Mesenchymal stem cell-derived exosome-inspired nanoformulations: a new frontier in targeted cancer therapy.
Jadhav RS, Koparde A, Kadam AB … +1 more , Kanaujia KA
Int J Pharm · 2026 Jun · PMID 42082061 · Publisher ↗
Mesenchymal stem cell (MSC)-derived exosome-inspired nanoformulations have recently been proposed as an emerging approach for targeted cancer therapies, which overcome the limitations of conventional cancer therapies, su...
Mesenchymal stem cell (MSC)-derived exosome-inspired nanoformulations have recently been proposed as an emerging approach for targeted cancer therapies, which overcome the limitations of conventional cancer therapies, such as low tumor selectivity, systemic toxicity, and the development of drug resistance. Exosomes, particularly MSC-derived exosomes, are known to offer an efficient and biocompatible approach for the targeted delivery of various therapeutic agents, including chemotherapeutic agents, to the tumor site. Here, we provide an integrative review on the unique aspects of MSC-derived exosomes (MSCEs)-inspired nanoformulations, including their tumor-targeting strategies, such as chemotaxis, receptor-mediated uptake, immune escape, and intracellular delivery, as well as their implications in cancer cell signaling. Further, the recent developments in the fabrication of bioengineering approaches for exosomes and the application of exosome-mimetic nanocarriers are also critically evaluated. In addition to therapeutic applications encompassing chemotherapy, RNA-based therapies, immunomodulation, and combination approaches, we provide a balanced discussion of the advantages, limitations, and key challenges related to large-scale production, standardization, and regulatory translation. Collectively, this review offers a unified framework bridging biological mechanisms and nanotechnological engineering, positioning MSCEs-inspired nanoformulations as next-generation platforms for precision oncology.
Effect of drug solubility, polymer, and filler on drug release from modified-release matrix tablets in hydroethanolic media.
Heinrich T, Bodmeier R, Dashevskiy A
Int J Pharm · 2026 Jun · PMID 42082060 · Publisher ↗
This study aimed to develop strategies to prevent accelerated drug release (alcohol-induced dose dumping) from modified-release matrix tablets in hydroethanolic media. Drugs with different solubility profiles (theophylli...
This study aimed to develop strategies to prevent accelerated drug release (alcohol-induced dose dumping) from modified-release matrix tablets in hydroethanolic media. Drugs with different solubility profiles (theophylline, propranolol HCl, paracetamol, and carbamazepine) were formulated with water-soluble or water-insoluble matrix formers, with optional addition of soluble or insoluble fillers. Drug release, medium uptake, and leaching were evaluated in 0.1 N HCl containing 0, 20, or 40% (v/v) ethanol. No release acceleration was observed for theophylline and propranolol HCl, which showed low solubility ratios between hydroethanolic and aqueous media (approximately 2). In contrast, paracetamol and carbamazepine (solubility ratio approximately 20) required formulation adjustments. For paracetamol, comparable release profiles across media were achieved using matrix formers with low medium uptake (e.g., Klucel® MXF or Kollidon® SR) or by incorporating a soluble filler such as lactose. For carbamazepine, the increased solubility in hydroethanolic media shifted the release mechanism from erosion-dominated to diffusion-dominated; similar release profiles were only obtained with hydrophilic polymers exhibiting relatively high erosion rates.
A 3D-printed diffusion cell for nail permeation testing.
Maisonneuve S, Vrignaud S, Pihet M … +4 more , Lagarce F, Crauste-Manciet S, Calvignac B, Lebreton V
Int J Pharm · 2026 Jun · PMID 42082059 · Publisher ↗
Evaluation of nail diffusion of active pharmaceutical ingredients (API) is a challenge but a necessity during pre-clinical studies of antifungals for the treatment of onychomycosis. Nevertheless, available model are expe...
Evaluation of nail diffusion of active pharmaceutical ingredients (API) is a challenge but a necessity during pre-clinical studies of antifungals for the treatment of onychomycosis. Nevertheless, available model are expensive or poorly accessible. Thus, a model based on a 3D printable cell and bovine hoof slices was designed. This model was assessed with two Amphotericine B (AmB) based preparations, a gel and a cream. After 7 days diffusion in the 3D printed cell, AmB was extracted from the hooves slices and quantitated by high-performance liquid chromatography (HPLC). Obtained AmB mean concentrations in hooves were 125.9 ± 7.4 µg/cm for AmB gel and 95.6 ± 15.9 µg/cmfor AmB cream, with "cm" referring to hoof thickness multiplied by diffusion surface. To complete the hoof diffusion test in the 3D printed cell, agar diffusion was also performed to access the ability of the API to diffuse through a water based matrix and to keep its antifungal properties. An ungual penetration model, using a 3D printed diffusion cell, that is simple to implement and easily accessible has been developed. Although it cannot produce results directly extendable to humans, it allows the comparison of several semi-solid formulation solutions with each other.
The role of pH changes during remote loading of setmelanotide in PLGA microspheres.
Wang S, Schwendeman SP
Int J Pharm · 2026 Jun · PMID 42070740 · Publisher ↗
The remote loading method enables aqueous, post-fabrication encapsulation of cationic peptides into PLGA microspheres via ion pairing between the deprotonated polymer carboxylate end groups and the basic amino acid side...
The remote loading method enables aqueous, post-fabrication encapsulation of cationic peptides into PLGA microspheres via ion pairing between the deprotonated polymer carboxylate end groups and the basic amino acid side chains and/or alpha amino group of the peptide. This encapsulation method can produce peptide loaded PLGA microspheres with competitive in vitro/in vivo performance to successful commercial PLGA-peptide products. However, this ion pairing loading technique also can be pH-dependent owing to the exchange of polymer protons with the peptide and the resulting pH effects on the polymer (and potentially peptide). Here, we investigated how pH dynamics govern remote loading performance for the model peptide setmelanotide, a permanent di-cation at neutral pH, by varying the buffer strength of the peptide loading solution (0.05 - 0.30 M HEPES) and microsphere attributes (porosity and PLGA molecular weight). The drug loading, first-week in vitro burst release, and microsphere surface morphology were examined. Increasing buffer concentration attenuated the pH drop during remote loading, preventing premature termination of ion pairing and thereby increasing encapsulation efficiency; lower molecular weight PLGA provided significantly higher loading and encapsulation efficiency across buffers (∼10% w/w with near-complete encapsulation with > 0.1 M buffer concentration). The largest pH decrease at 0.05 M HEPES (∼2 units) was associated with a substantially reduced initial burst (∼5% in the first week) irrespective of microsphere initial surface porosity, whereas the smallest pH change at 0.30 M buffer concentration yielded the highest burst (∼20% in the first week), consistent with observed surface polymer healing changes before and after remote loading. Guided by the findings, a low pH rinse (0.2 M MES buffer, pH ∼6.0) applied to a high-burst formulation was shown to reduce the initial burst release in vitro in the first 24 h from ∼7% to ∼3%. Overall, this work identifies process and material parameters that can be used to optimize pH effects of remote loading to minimize burst release while maximizing peptide loading via the remote loading method.
Exploring the impact of nucleotide length on lipid nanoparticle structure and properties.
Hammel M, Fan Y, Kim LJ … +5 more , Zang N, Xiao B, Calio A, Yen CW, Hura GL
Int J Pharm · 2026 Jun · PMID 42070739 · Publisher ↗
Lipid nanoparticles (LNPs) are versatile carriers for nucleic acid (NA) therapeutics, including ASOs, siRNA, mRNA, and poly-IC. While lipid composition is known to influence LNP properties, the impact of NA length on mor...
Lipid nanoparticles (LNPs) are versatile carriers for nucleic acid (NA) therapeutics, including ASOs, siRNA, mRNA, and poly-IC. While lipid composition is known to influence LNP properties, the impact of NA length on morphology and internal structure is less understood, particularly during the stages of carrier-cargo assembly. Here, we examine NA length and lipid composition immediately after mixing using high-throughput SAXS, dynamic light scattering, and cryogenic electron microscopy. All LNPs form ordered NA/lipid compartments, with longer NAs promoting inverse hexagonal (H) phases and larger intercompartment distances. In contrast, short NAs, especially in formulations with SM102 ionizable lipid, favor lamellar phases. SAXS peak deconvolution quantifies ordered versus disordered phases via a Robustness of Ordered Phase factor, which correlates with particle size and encapsulation efficiency. Formulations with MC3 ionizable and DOPE helper lipids exhibit the most stable H-phase packing, highlighting the role of helper-lipid curvature in compartment stabilization. Variations in NA compartmentalization indicate differences in payload capacity, offering a framework for rational LNP design across diverse nucleic acid cargos.
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