International Journal of Pharmaceutics最新文献

{"title":"Mesenchymal stem cell-derived exosome-inspired nanoformulations: a new frontier in targeted cancer therapy.","authors":"Ranjit S Jadhav, Akshada Koparde, Akshay B Kadam, Kunal Agam Kanaujia","doi":"10.1016/j.ijpharm.2026.126929","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126929","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"698 ","pages":"126929"},"PeriodicalIF":5.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pH changes during remote loading of setmelanotide in PLGA microspheres.","authors":"Shuying Wang, Steven P Schwendeman","doi":"10.1016/j.ijpharm.2026.126943","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126943","url":null,"abstract":"<p><p>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 has been shown to produce peptide loaded PLGA microspheres with competitive in vitro/in vivo performance to successful commercial PLGA-peptide products. However, this ion pairing loading technique has been shown to be pH dependent owing to the exchange of polymer proton 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 surface porosity, whereas the smallest pH change at 0.30 M buffer 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 while maximizing peptide loading via remote loading method.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126943"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the impact of nucleotide length on lipid nanoparticle structure and properties.","authors":"Michal Hammel, Yuchen Fan, Lee Joon Kim, Nanzhi Zang, Baixue Xiao, Antonino Calio, Chun-Wan Yen, Greg L Hura","doi":"10.1016/j.ijpharm.2026.126944","DOIUrl":"10.1016/j.ijpharm.2026.126944","url":null,"abstract":"<p><p>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_II) 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_II-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.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126944"},"PeriodicalIF":5.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into ultrasound-responsive implantable drug delivery systems.","authors":"Yujie Lu, Mohammad Albraikat, Juan L Paris, Jiaqi Gao, Huaidong Yang, Masoud Adhami, Eneko Larrañeta","doi":"10.1016/j.ijpharm.2026.126913","DOIUrl":"10.1016/j.ijpharm.2026.126913","url":null,"abstract":"<p><p>Stimulus-responsive drug delivery systems have been widely explored to achieve controlled, site-specific drug release. Among various stimuli, ultrasound offers several advantages as an external trigger, including cost-effectiveness, deep tissue penetration, and precise spatiotemporal control. While hydrogel and microbubble associated systems have been extensively studied, reservoir-type implants remain underexplored despite their potential for long-term therapy. In this study, a biodegradable polymeric reservoir implant with porous rate-controlling membrane was developed, with systematically evaluated ultrasound-responsive behaviour. Biosafety was assessed through temperature monitoring, mechanical index calculations, and histological analysis, leading to the selection of 3 MHz, 3 W/cm² ultrasound for 5 min with 9.13° C increase as a safe operating condition. Under the selected setting, ultrasound significantly enhanced drug release for around 9.7-fold by accelerating drug dissolution and diffusion, without altering the structural properties of the release membrane. Collectively, these findings provide mechanistic insight into ultrasound-responsive reservoir implants and support their potential application in managing chronic conditions, where controllable, on-demand drug release is highly desirable.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126913"},"PeriodicalIF":5.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Covalent functionalization of polymeric nanoparticles prepared from nano-emulsion templates for gene silencing and antioxidant delivery at neuronal level.","authors":"Marta Bel-Esteve, Marc Carrasco, Núria Moral, Anna Aviñó, Carme Fàbrega, Ramon Eritja, Jose Antonio Del Río, Jordi Duran, Cristina Fornaguera, Carlos Rodríguez-Abreu, Santiago Grijalvo","doi":"10.1016/j.ijpharm.2026.126918","DOIUrl":"10.1016/j.ijpharm.2026.126918","url":null,"abstract":"<p><p>Poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles (PLGA NPs) have proven to be effective as potential drug delivery systems. The presence of carboxylate groups on their surface facilitates the development of multifunctional NPs enhancing therapeutic efficacy through synergetic effects. Our study describes the preparation of PLGA NPs using oil-in-water polymeric nano-emulsions, generated via a phase inversion composition low-energy emulsification method. Rosmarinic acid (RA), a phytochemical with neuroprotective effects, and an antisense oligonucleotide (ASO) were selected respectively as a phytochemical to be entrapped and as a ligand to decorate the surface of PLGA nanoparticles respectively, aiming to enhance ASO delivery to neuronal cells. Physicochemical characterization confirmed that RA and ASO incorporation preserved colloidal stability, with no adverse effect on particle size, surface charge, or morphology. In vitro-controlled release experiments showed a cumulative RA release of ca. 12% over 24 h governed by a semi-Fickian diffusion mechanism after adjusting to different equation models. Importantly, RA entrapment displayed measurable radical scavenging capacity, leading to a EC₅₀ of 76 ± 0.9 μg·mL^-1. Cell culture experiments confirmed biocompatibility in both a non-cancer cell line (HEK293) and neuroblastoma cell model (SH-SY5Y). Uptake studies revealed efficient internalization of PLGA NPs by SH-SY5Y cells and primary murine neurons, promoting gene silencing of luciferase expression (53.7 ± 7.9%). Together, these results show a modular PLGA nanoplatform that enables the simultaneous incorporation of an antioxidant payload and a covalently grafted antisense oligonucleotide, allowing independent assessment of redox modulation and gene silencing in neuronal models.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126918"},"PeriodicalIF":5.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in DNA hydrogels for biomedical applications.","authors":"Jiaqi Liang, Jianbin Shi, Boyu Jing, Shenwu Zhang, Xiao Kuang","doi":"10.1016/j.ijpharm.2026.126928","DOIUrl":"10.1016/j.ijpharm.2026.126928","url":null,"abstract":"<p><p>DNA hydrogels that integrate programmable DNA into three-dimensional networks offer unique advantages in precise target recognition and efficient signal transduction. These properties enable them to overcome critical limitations of conventional platforms, such as poor stability, matrix interference, and high cost, thereby making them highly attractive for biomedicine. Recent research has focused on customizing DNA hydrogels to enhance sensing performance and expand therapeutic potential. This review systematically summarizes recent advances of DNA hydrogels in biosensing and drug delivery. We first introduce major synthesis routes and design principles. These include crosslinking density regulation and stability protection. Then, we analyze the mechanisms of DNA hydrogels in biosensing and drug delivery. Next, we review their applications in medical detection, disease treatment, and theranostic platforms. Finally, we discuss current challenges and future directions. This review aims to provide a reference for rational design and translational application of DNA hydrogel systems.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126928"},"PeriodicalIF":5.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microbubbles manufactured using a tissue homogeniser: DoE-guided optimisation for a narrower size distribution and higher yield.","authors":"Colm S O'Reilly, Abdul W Basit, Mine Orlu, Eleanor Stride, Gareth LuTheryn, Michael D Gray, Dario Carugo","doi":"10.1016/j.ijpharm.2026.126912","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126912","url":null,"abstract":"<p><p>Microbubbles are clinically approved as ultrasound contrast agents because they oscillate in response to ultrasound (cavitation) and are increasingly explored for therapeutic applications. Microbubble diameter governs dynamic behaviour under ultrasound; therefore, a narrow size distribution is essential for predictable performance and optimal responsiveness. However, producing phospholipid-coated microbubbles with narrow distributions using simple methods remains challenging. This study evaluated a bead-type tissue homogeniser as an alternative to probe sonication for generating DSPC-PEG40S (9:1), air-filled microbubbles, using design of experiments (DoE) to identify influential parameters. A three-level full-factorial design assessed effects on mean diameter, concentration, and polydispersity index (PDI). Optical microscopy with an ImageJ analysis pipeline quantified size and concentration, while passive cavitation detection characterised acoustic response. Liquid volume significantly affected mean diameter, concentration, and PDI, whereas homogenisation speed significantly influenced PDI only. Response optimisation identified 5 m·s⁻¹, 45 s, and 500 µl as optimal speed, time, and volume settings. Compared with sonication, homogenisation generated less heat and achieved higher production rates. Resulting microbubbles were smaller, more uniform in size, and higher in concentration. At 37 °C, homogenised suspensions remained above 10⁸ MB/ml at 6 h, indicating improved short-term stability. Acoustic emissions increased with pressure and were comparable between methods when normalised to gas volume. Overall, bead homogenisation offers a simple, less thermogenic, high-throughput method for reproducible phospholipid microbubble production.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126912"},"PeriodicalIF":5.2,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients in-use stability and safety of repacked delayed-release capsules of sodium divalproex.","authors":"Mariame A Hassan, Ziyaur Rahman, Mansoor A Khan","doi":"10.1016/j.ijpharm.2026.126927","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126927","url":null,"abstract":"<p><p>Divalproex Sodium (DVS) is an antiseizure narrow therapeutic index drug. Despite its effectiveness, the primary reason for reduced compliance and/or treatment discontinuation is intolerance to its gastric side effects. Delayed-release forms to alleviate gastric side effects are available as enteric coated beads (sprinkles) in capsules. Four sprinkles (A-D), marketed as interchangeable, were compared and assessed for quality changes after storage at 30 °C/75%RH in pharmacy vials, and at 40 °C/75% RH and 25 °C/60% RH in HDPE bottles for 3 months. The results revealed that initially, all products differed in their gastric resistance releasing from 3.8 to 39% of the drug. Gastric delivery further increased significantly after storage at higher temperatures to 35-45% among all products. Release also varied initially in buffer medium, especially at 1 h (12.6 ± 1.1, 65.8 ± 0.2, 0.0 ± 0.0 and 10.8 ± 0.3% for products A, B, C and D, respectively), reflecting a controlled release pattern over 4-6 h in three products. Following storage, the drug release increased at all conditions. The capsules parts adhered together, and beads fused into coherent masses in response to environmental changes. The FTIR spectra showed chemical changes in the beads. Overall, the results indicated significant variability among the tested products that could lead to significant side effects, unpredictability in drug absorption and serum level fluctuations, altogether culminating in seizures remittance. The study highlights the pharmaceutical quality as a critical, yet overlooked, player in improving patients' compliance and therapeutic outcomes. Moreover, it draws attention to the importance of reviewing dispensing and storage recommendations for this drug.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126927"},"PeriodicalIF":5.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-inspired implantable therapeutic systems: quantitative structure-property-function design of hierarchical biomaterials.","authors":"Neha Maheshwari, Mayank Sharma, Rahul Maheshwari","doi":"10.1016/j.ijpharm.2026.126910","DOIUrl":"10.1016/j.ijpharm.2026.126910","url":null,"abstract":"<p><p>Plant-derived architectures provide a unique reservoir of hierarchical, anisotropic, and transport-optimized design principles that can be systematically translated into functional biomaterials for regenerative implants. Unlike conventional scaffold engineering approaches that rely on artificially generated porosity and isotropic architectures, plant tissues exhibit evolutionarily optimized vascular networks, graded mechanical stiffness, and stimulus-responsive morphologies that directly address challenges in mass transport, stress distribution, and adaptive integration in biomedical implants. This review critically examines how plant structural hierarchies, from cellulose microfibril alignment to multichannel vascular bundles, are mechanistically mapped onto modern biofabrication platforms, including decellularization, extrusion-based 3D printing, direct ink writing, electrospinning, and 4D printing. Particular emphasis is placed on quantitative structure-property-function relationships, such as anisotropic modulus ratios (E||/E⊥), channel diameter-diffusion coupling, swelling-induced curvature programming, and surface energy-biofouling interactions, that govern biological outcomes including angiogenesis, osteogenesis, myogenic alignment, and anti-infective performance. Representative case studies demonstrate that plant-inspired multichannel scaffolds enhance vascular infiltration and bone regeneration in vivo, aligned cellulose-based systems enable programmable shape morphing for minimally invasive deployment, and biomimetic surface microtopographies reduce fouling without antibiotic reliance. However, critical translational challenges remain, including immunological validation of decellularized plant matrices, mechanical fatigue under cyclic physiological loading, lubricant stability in slippery interfaces, and scalability under Good Manufacturing Practice (GMP) conditions. By integrating plant biomechanics, materials science, and advanced biofabrication, plant-inspired biomaterials emerge as a promising, yet early-stage strategy for engineering adaptive, vascularized, and multifunctional implants. Future progress will depend on rigorous quantitative validation, long-term in vivo performance studies, and standardized manufacturing frameworks that bridge biomimetic design with clinical translation.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126910"},"PeriodicalIF":5.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting the viability of pharmaceutical formulations for continuous direct compression using machine learning approaches.","authors":"Laura Pereira Diaz, Stéphanie Marchal, Paul Kroll, Albert Hofstetter, Moritz Lang, Patrick M Piccione, Cameron J Brown, Mohammad Salehian, Alastair J Florence","doi":"10.1016/j.ijpharm.2026.126911","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2026.126911","url":null,"abstract":"<p><p>Pharmaceutical formulation is the activity in which the chemical substances that form a final medicinal product are combined, including the active pharmaceutical ingredient and excipients. Changes in formulation from variations in excipients, their composition, or variations in drug loading can impact bulk properties such as powder flowability. Such properties, in turn, may impact subsequent manufacturing processes adversely. More subtle changes, for instance in the physical properties of API, such as particle size and shape, can also influence the manufacturability of the drug product. It is therefore important to use state-of-the-art techniques to predict formulation properties, in particular for manufacturability. In this context, Artificial intelligence and Machine Learning (ML) have emerged as potential tools to optimise the transition from formulation development to manufacturing and thus, the use of digital design and data-driven models provides the prospect to accelerate these important development steps. This paper presents three complementary ML models that, when used together, support early assessment of the viability of pharmaceutical formulations for continuous direct compression (cDC). The combined modelling approach provides a practical framework for predictive screening of formulation viability and for supporting more informed decision-making during formulation development.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"126911"},"PeriodicalIF":5.2,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147815304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}