European Journal Of Pharmaceutics And Biopharmaceutics[JOURNAL]
Sun
200 papers
Excipients: New opportunities for complex challenges - USP's approaches.
Sheehan C, Liu TJ, Zhang P … +2 more , Wang H, Chang A
Eur J Pharm Biopharm · 2026 Jun · PMID 41802499 · Publisher ↗
The quality of excipients is important since they can make up to about 90% of the total mass/volume of the drug product. Traditionally, excipients specifications were established with a focus on quality for intended use...
The quality of excipients is important since they can make up to about 90% of the total mass/volume of the drug product. Traditionally, excipients specifications were established with a focus on quality for intended use in the drug product and less on excipient composition, and physical and chemical properties, however, the increasing demand for high quality excipients used in the development of nanomedicines and novel delivery systems requires higher quality and purity, e.g., use of phospholipids in development of Covid-19 vaccine nanomedicine delivery systems. USP is collaborating with stakeholders to address the lack of standardized test methods for complex/polymeric type excipients (e.g., phospholipids/LG polymers) offering new solutions and help with excipient compositional and variability issues along with associated environmental aspects. By expanding its offerings through its "emerging standards" new model for stakeholder engagement, USP is more flexible in its solutions offerings that favor earlier interaction in the genesis of quality standards in a more iterative way. This publication will provide an overview of evolving compendial approaches (e.g., standalone chapters) and expanded solutions and offerings (use of analytical reference materials (ARMS), associated application (App) notes, and technical guides).
Automated microstructural characterization of hydrogels using deep instance segmentation and graph-based agglomerate analysis.
Khosravi H, Mulrennan K, Monteagudo E … +2 more , Unnikrishnan S, Donovan J
Eur J Pharm Biopharm · 2026 Jun · PMID 41794191 · Publisher ↗
The performance and stability of pharmaceutical hydrogels depend on microstructural features such as particle size and agglomeration. Characterization of these features is commonly performed through manual microscopic as...
The performance and stability of pharmaceutical hydrogels depend on microstructural features such as particle size and agglomeration. Characterization of these features is commonly performed through manual microscopic assessment, which can be subjective when particle boundaries are indistinct or agglomerates lack clearly defined interfaces. This study applies computer vision to automate the analysis of hydrogel micrographs, including particle segmentation, agglomerate identification, and the extraction of size-related morphological parameters. Two deep instance segmentation networks, the Mask R-CNN and the Mask2Former, were applied for this purpose. This study introduced a particle dilation and a graph-centric approach for agglomerate identification, differing from prior methods where agglomerates were annotated individually, thus mitigating some annotation challenges. The networks, trained on a hydrogel database, exhibited an Average Precision of 92.47% for Mask R-CNN and 91.86% for Mask2Former. The Mask2Former demonstrated superior Average Recall (AR) at 76.6%, compared to Mask R-CNN's 72.32%. This study pioneers the application of Mask2Former, a Vision Transformer-based network, for particle segmentation which had superior AR performance. Considering the subjective nature of annotation for hydrogel micrographs, where false positives can be considered as valid particles, this study recommends the inclusion of AR as a metric for model selection. Furthermore, the extracted morphological features from segmented images showed close agreement with manual measurements. This workflow has potential to support formulation development and quality assessment in pharmaceutical settings.
Release of rapamycin from core-multishell nanocarriers topically applied on ex vivo human skin probed by scanning transmission X-ray microscopy.
Germer G, Rajes K, Ohigashi T … +7 more , Yuzawa H, Kosugi N, Flesch R, Haag R, Rancan F, Vogt A, Rühl E
Eur J Pharm Biopharm · 2026 Jun · PMID 41786093 · Publisher ↗
Delivery of rapamycin loaded on core-multishell nanocarriers with different architectures supporting redox-induced drug release is investigated on human skin ex vivo by scanning transmission X-ray microscopy (STXM) near...
Delivery of rapamycin loaded on core-multishell nanocarriers with different architectures supporting redox-induced drug release is investigated on human skin ex vivo by scanning transmission X-ray microscopy (STXM) near the O 1s-absorption edge (520-565 eV). The local concentration of the drug and nanocarriers in skin sections is obtained from linear combination modeling using reference spectra of the drug, nanocarriers, and untreated skin. This allows us to probe selectively rapamycin and nanocarriers as a function of exposure time reaching up to 5 days. Additionally, skin samples were treated with dibenzoyl peroxide (DBPO) to induce oxidative stress and simulate the local redox environment found in skin inflammatory conditions. It is shown that rapamycin and nanocarriers have different penetration profiles, which shed light on the drug transport and release mechanisms. These results make use of high spatial resolution at full chemical selectivity reaching down to 75 nm and are compared to skin penetration of topically applied rapamycin in different formulations. They highlight unique capabilities and the future potential of drug transport by polymeric drug nanocarriers.
Optimizing spray-dried liposomes for pulmonary delivery: impact of lipids composition and of drying parameters using experimental design.
Bya LA, Dinh TN, Penoy N … +8 more , Sacré PY, Bottero B, Cataldo D, Hendrickx E, Conrard L, Evrard B, Piel G, Lechanteur A
Eur J Pharm Biopharm · 2026 Jun · PMID 41771307 · Publisher ↗
Liposomes are promising carriers for pulmonary drug delivery due to their biocompatibility and controlled-release properties. However, their stability in aqueous suspension is limited, leading to aggregation and reduced...
Liposomes are promising carriers for pulmonary drug delivery due to their biocompatibility and controlled-release properties. However, their stability in aqueous suspension is limited, leading to aggregation and reduced therapeutic efficiency. Converting liposomal dispersions into dry powders for inhalation (DPIs) is a potential strategy to overcome these limitations. Spray-drying (SD) is particularly attractive for this purpose, offering precise control over particle properties along with speed, cost-efficiency, and scalability. Yet, the thermal and mechanical stresses involved in this process and their effects on liposomal integrity remain poorly understood, limiting its broader application. In this study, we developed a systematic framework integrating Design of Experiments (DOE) with scale-up-oriented processing, combining supercritical fluid technology (PGSS) for liposome formation with subsequent spray-drying of high solid content suspensions. Two complementary DoE approaches were applied: DOE optimized drying parameters and carbohydrate type, testing trehalose and hydroxypropyl-β-cyclodextrin (HPβCD), while DOE assessed the effects of active pharmaceutical ingredients (APIs) hydrophobicity, lipid composition (1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)- (DSPE-PEG) percentage), and carbohydrate-to-liposome ratio. Optimized spray-dried powders exhibited preserved liposome structure (mean diameter < 200 nm, narrow polydispersity index (PdI), near-neutral zeta potential (ZP)), favorable aerodynamic properties (∼3 µm, extra-fine particle fraction (eFPF) > 20% and fine particle fraction (FPF) > 60%), low residual moisture (<5%), and high drying yields (>75%). Mechanistic insights revealed that HPβCD significantly protects liposomes during atomization, while drug retention was governed by PEGylated lipid content, lipid-to-carbohydrate ratio, and API hydrophobicity. Co-encapsulation of clinically relevant drug combinations (formoterol/budesonide and ciclesonide/indacaterol) produced uniform powders with efficient aerosolization, highlighting the therapeutic potential of these formulations. Collectively, these results establish a robust, scalable, and reproducible approach for designing liposomal DPIs, balancing formulation composition, excipient selection, and process parameters. This study demonstrates that strategic integration of scalable technologies can reconcile structural stability, aerodynamic performance, and manufacturability, paving the way for the industrial translation of liposomal dry powders for targeted pulmonary therapies, including asthma and chronic obstructive pulmonary disease (COPD).
Coincidental dependence of low endotoxin recovery and lipopolysaccharide aggregate size on formulation composition and presence of multivalent cations.
Gorman A, Moore S, Golovanov AP
Eur J Pharm Biopharm · 2026 May · PMID 41763413 · Publisher ↗
Low Endotoxin Recovery (LER) is the loss of ability of the industry-standard lipopolysaccharide (LPS)-detection method, the Limulus Amebocyte Lysate (LAL) assay, to detect LPS in formulations containing chelating agents...
Low Endotoxin Recovery (LER) is the loss of ability of the industry-standard lipopolysaccharide (LPS)-detection method, the Limulus Amebocyte Lysate (LAL) assay, to detect LPS in formulations containing chelating agents and surfactants. LER may potentially interfere with the testing of biopharmaceutical formulations for the absence of endotoxins. The mechanism of LER remains unresolved, with some suggesting that it may be caused by changes in LPS aggregate size. Here, we offer a comprehensive analysis of the effects of chelating agents, surfactants and multivalent cations on both LPS masking and LPS aggregate sizes. In the presence of certain divalent or trivalent cations, surfactants and chelating agents an apparent correlation between LER effects and a reduction in the size of LPS aggregates is observed. However, for other examples of the same type of excipient no such correlation exists. This indicates that any previously proposed correlation between aggregate size and LER is merely coincidental and does not contribute to the LER mechanism. Additionally, adding Mg cations fully prevented LER over 7 days, while trivalent cations only temporarily delayed it, raising a question about the role of electrostatic interactions and aggregate rearrangements in the LER effect. We propose that, despite the apparent general reduction in aggregate sizes in some LER conditions, the mechanism of LER should be attributed to modification of the surface of LPS aggregates, rather than their size or LPS disaggregation. These findings can be used to direct further research into LER mechanisms and to reconsider the strategies to mitigate LER in LAL assays.
Incorporating immunostimulatory lipids into lipid nanoparticles: exploring expression and immune responses.
Evdokimou M, Alaqabani H, Hussain M … +1 more , Perrie Y
Eur J Pharm Biopharm · 2026 Jun · PMID 41759597 · Publisher ↗
Lipid nanoparticles (LNPs) are a well-established platform for mRNA vaccine delivery, offering efficient encapsulation and intracellular delivery. However, opportunities remain to understand how lipid composition influen...
Lipid nanoparticles (LNPs) are a well-established platform for mRNA vaccine delivery, offering efficient encapsulation and intracellular delivery. However, opportunities remain to understand how lipid composition influences immunogenicity. In this study, we investigated the incorporation of dimethyldioctadecylammonium bromide (DDAB), a permanently cationic lipid with reported immunostimulatory properties, into SM-102 LNPs. The fixed positive charge of DDAB at physiological pH can enhance cellular uptake, support local antigen expression, and promote immune activation, all features desirable for vaccine applications. LNPs were prepared with a fixed combined content of 50 mol% SM-102 and DDAB, blended at varying molar ratios (50:0 to 0:50), alongside 10 mol% DSPC, 38.5 mol% cholesterol, and 1.5 mol% DMG-PEG2000. Formulations were characterised for particle size, polydispersity index, zeta potential, and mRNA encapsulation efficiency. Physicochemical characterisation showed that increasing DDAB content led to a progressive increase in particle size while maintaining low polydispersity, neutral zeta potential, and high mRNA encapsulation efficiency across all formulations. Incorporation of ≥ 40% DDAB also altered the apparent pKa profile of the LNPs, consistent with an increasing dominance of permanent cationic charge. In vitro transfection assays in HEK293 cells demonstrated enhanced expression with DDAB-containing LNPs, with the 10% DDAB formulation achieving a six-fold increase in mRNA expression compared to SM-102-only LNPs. However, in vivo luciferase expression following intramuscular administration was significantly reduced in DDAB-LNPs compared to the SM-102 LNPs (p < 0.05). Immunisation studies showed that low-level DDAB substitution (10-30%) did not significantly alter antibody responses, while higher levels (≥40%) reduced immunogenicity, indicating no overall advantage to incorporating DDAB into SM-102 LNP vaccines.
Corrigendum to "Reflection paper on the APV workshop on in vitro performance testing of topically applied and topically acting substances" [Eur. J. Pharm. Biopharm. 220 (2026) 114971].
Lunter D, Gorissen S, Herbig M … +2 more , Hukauf M, Eichner A
Eur J Pharm Biopharm · 2026 May · PMID 41748396 · Publisher ↗
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From vial to prefilled delivery devices in autoimmune diseases: Exploring the formulation and technological pharmaceutical challenges.
Vieira ACF, Costa G, Silva I … +6 more , Maurício S, Martins-Pimenta D, Almeida H, Bell V, Veiga F, Paiva-Santos AC
Eur J Pharm Biopharm · 2026 May · PMID 41747875 · Publisher ↗
The use of medicines in the daily clinical practice and meeting the desired effectiveness is many times dependent upon patient experience and compliance with the therapy. This is particularly relevant in chronic diseases...
The use of medicines in the daily clinical practice and meeting the desired effectiveness is many times dependent upon patient experience and compliance with the therapy. This is particularly relevant in chronic diseases, such as the case of autoimmune diseases. The management of autoimmune diseases often involves the regular administration of biologic therapies, which require precise dosing and consistent adherence to treatment regimens. Prefilled syringes, prefilled pens, and auto-injectors have emerged as pivotal tools in this therapeutic landscape, offering significant benefits in terms of convenience, safety, and accuracy. Despite the R&D efforts involved in the repurposing of the pharmaceutical form from a vial to a ready-to-use prefilled syringe, the time saved for both doctor and patient, and the convenience to the patient are intangible values. This review provides a comprehensive overview of the use of drug prefilled delivery devices in the treatment of autoimmune diseases. A special focus is given to the formulation differences when comparing vials with prefilled delivery devices, addressing the modifications in terms of strength, primary packaging, shelf life, and excipients. It delves into the technological advancements that have led to the development of these devices, describing the composition and function of each component on the currently marketed injectable drug delivery devices for autoimmune diseases. Through a review of current research and clinical practices, this study highlights the critical role these devices play in enhancing the effectiveness of autoimmune disease management, ultimately leading to better patient outcomes.
Quaternized chitosan-coated liposomes enable pH-independent nasal mucoadhesion and a sustained local depot for mometasone furoate.
Jiang M, Yuan H, Zhang W … +7 more , Dong Y, Zhang Y, Yin T, He H, Gou J, Wang Y, Tang X
Eur J Pharm Biopharm · 2026 May · PMID 41747874 · Publisher ↗
Limited nasal deposition and rapid clearance compromise the effectiveness of intranasal therapy for allergic rhinitis. Quaternized chitosan (QCS), which carries a permanent positive charge at the near-neutral pH of the n...
Limited nasal deposition and rapid clearance compromise the effectiveness of intranasal therapy for allergic rhinitis. Quaternized chitosan (QCS), which carries a permanent positive charge at the near-neutral pH of the nasal cavity, overcomes the pH-dependent limitations of conventional chitosan coatings. In this study, quaternized chitosan-modified liposomes encapsulating mometasone furoate (QCS-MF-Lip) were developed to enhance mucoadhesion and establish a local drug depot. The optimized formulation exhibited a small particle size (170 ± 1 nm) with a narrow size distribution (PDI 0.232 ± 0.011). QCS-MF-Lip showed a 5.26-fold higher mucin-binding affinity and approximately 4.7-fold greater ex vivo mucosal retention (19.59 ± 0.62 μg·cm⁻) compared with unmodified liposomes and the commercial spray Nasonex®, respectively. In a rat model of allergic rhinitis, QCS-MF-Lip significantly alleviated symptoms and demonstrated superior therapeutic efficacy relative to Nasonex®, as reflected by reduced histamine levels and enhanced anti-inflammatory effects. These results suggest that permanently cationic QCS is a promising strategy for pH-independent nasal mucoadhesion and the establishment of a local intranasal drug depot.
L-Alaninium borneol ester flurbiprofenate: a dual-function ionic carrier for enhanced solubility and transdermal delivery.
Bilska K, Nowak A, Zagórska-Dziok M … +4 more , Ziemlewska A, Nizioł-Łukaszewska Z, Struk Ł, Ossowicz-Rupniewska P
Eur J Pharm Biopharm · 2026 May · PMID 41734874 · Publisher ↗
Flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), suffers from poor aqueous solubility and limited skin permeability, hindering its bioavailability for both oral and transdermal delivery. In this study, a nove...
Flurbiprofen, a nonsteroidal anti-inflammatory drug (NSAID), suffers from poor aqueous solubility and limited skin permeability, hindering its bioavailability for both oral and transdermal delivery. In this study, a novel ionic conjugate, L-alaninium borneol ester flurbiprofenate (AlaOBor∙F), was synthesized via two-step routes involving esterification and salt formation. Two synthetic strategies were evaluated and compared: direct acid-catalyzed esterification using thionyl chloride and an alternative coupling approach employing dicyclohexylcarbodiimide and 4-dimethylaminopyridine with Boc-protected amino acids. The resulting compounds were fully characterized by NMR, FT-IR, DSC, TG, and XRD. AlaOBor∙F exhibited significantly improved physicochemical properties compared to flurbiprofen, including enhanced solubility (0.229 g/dm in water vs. 0.028 g/dm for flurbiprofen), reduced lipophilicity (logarithmic partition coefficient: 2.03), and superior transdermal permeability in ex vivo Franz diffusion cell studies (steady-state flux: 27 µg/cm·h). Additionally, AlaOBor∙F retained the antioxidant potential of flurbiprofen and demonstrated no significant cytotoxicity in human fibroblasts and THP-1 monocytes up to 100 µg/mL. Furthermore, in lipopolysaccharide-stimulated monocytes, the derivative reduced interleukin-1β, interleukin-6, and cyclooxygenase-2 expression in a dose-dependent manner, surpassing the anti-inflammatory effects of flurbiprofen. These results suggest that ionic pairing with L-alaninium borneol ester is a promising strategy to enhance solubility, permeability, and therapeutic efficacy of NSAIDs for topical administration.
Mitigation of viral particle interaction with glass surfaces improved Ad26 vaccine quality and long-term stability.
Mönkäre J, Labovitiadi O, da Silva Freire JC … +2 more , Burgers P, Capelle MAH
Eur J Pharm Biopharm · 2026 May · PMID 41724451 · Publisher ↗
Therapies and vaccines based on novel modalities (e.g., viral vectors) often suffer from poor thermal stability warranting deep-frozen storage. By improving stability of these drug products (DP) at refrigerated (2-8°C) c...
Therapies and vaccines based on novel modalities (e.g., viral vectors) often suffer from poor thermal stability warranting deep-frozen storage. By improving stability of these drug products (DP) at refrigerated (2-8°C) conditions, their distribution and administration could be facilitated. In this study, Adenovirus 26-based (Ad26) vaccine drug product had short-term instability at refrigerated conditions during the clinical development. This observation was investigated by a combination of conventional and innovative analytical tools, such as in situ monitoring of viral particle concentration in vials. Adsorption of viral particles to the glass vial surface was identified as main root-cause for poor stability, and this was particularly observed upon vial inversion due to the additional loss of viral particles to the previously unexposed glass surface. After the assessment of different mitigation options, standard glass vials were replaced with siliconized glass vials as they efficiently prevented viral particle adsorption on the glass surface compared to reformulation using excipients. Surprisingly, use of siliconized glass vials improved short as well as long-term stability, as Ad26 DP manufactured at commercial scale remained stable, with practically no changes of infectious titer loss, for at least 30 months at refrigerated conditions. In conclusion, the primary container selection can have a critical impact on viral vector stability. Consequently, container selection and container surface-product interactions should be assessed as part of early formulation and process development.
Targeting dopamine pathways with hybrid molecules: Emerging outlook for cancer treatment.
Koch P, Pielaszkiewicz N, Małek K … +2 more , Kamysz W, Kleczkowska P
Eur J Pharm Biopharm · 2026 May · PMID 41724450 · Publisher ↗
Dopamine (DA)-related signaling has increasingly been recognized as a contributor to cellular regulation, affecting pathways associated with growth, survival, and receptor-mediated signaling. This understanding has motiv...
Dopamine (DA)-related signaling has increasingly been recognized as a contributor to cellular regulation, affecting pathways associated with growth, survival, and receptor-mediated signaling. This understanding has motivated the development of hybrid therapeutic platforms that combine dopaminergic modulation with additional strategies, such as receptor co-targeting and selective drug delivery. These systems encompass diverse molecular formats, including multifunctional peptide chimeras acting on dopaminergic and somatostatin receptors, as well as DA-functionalized nanomaterials or polymeric conjugates. Collectively, these hybrids demonstrate the potential for enhanced pharmacologic precision, improved intracellular accumulation, and reduced off-target effects as compared to those of conventional compounds. Despite promising preclinical evidence, multiple barriers remain before these technologies can be translated clinically. This review synthesizes current advances in DA-pathway-targeting hybrid constructs, explores their mechanistic rationale, and highlights the major biological and translational challenges that must be addressed to support their development.
Topical application of Clostridium butyricum by an anaerobic hydrogel for accelerated diabetic wound healing through selective bacteria inhibition and ROS scavenging.
Shen H, Chen J, Zheng W … +3 more , Cao Y, Du T, Wu W
Eur J Pharm Biopharm · 2026 May · PMID 41722740 · Publisher ↗
Selective inhibition of harmful bacteria without affecting skin symbiotic probiotics and selective scavenging of highly toxic reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and peroxynitrite anions (ONOO)...
Selective inhibition of harmful bacteria without affecting skin symbiotic probiotics and selective scavenging of highly toxic reactive oxygen species (ROS) such as hydroxyl radicals (•OH) and peroxynitrite anions (ONOO) are new requirements for more precise treatment of diabetic ulcer wounds. Achieving either is challenging, simultaneous achievement remains unreported. Clostridium butyricum (C. butyricum) inherently offers selective antibacterial action and produces hydrogen, specifically scavenging •OH and ONOO, showing great potential for diabetic wound treatment. However, as an anaerobic bacterium, its anaerobic nature limits topical application in normoxic environments on the skin. To overcome this, we developed a novel hydrogel creating an internal anaerobic microenvironment via the oxygen-depleting reaction between vanillin and laccase. Serving as a carrier, this hydrogel ensures internalized C. butyricum maintains activity in normoxia, enabling effective dual functions: selective bacterial inhibition and selective ROS scavenging. In vivo studies demonstrate the significant efficacy of this C. butyricum-loaded hydrogel in promoting diabetic wound healing. This work pioneers the topical therapeutic use of C. butyricum for wound treatment.
From ascorbic acid to N-acetylcysteine: self-assembled clarithromycin liquid crystals as a new generation of carrier-free antibiotics.
Bartolilla A, Zoppi A, Basiglio B … +2 more , Longhi MR, Aiassa V
Eur J Pharm Biopharm · 2026 May · PMID 41722739 · Publisher ↗
Antimicrobial resistance demands innovative molecular strategies to enhance antibiotic efficacy while minimizing the use of excipients. Building on the previously reported clarithromycin: ascorbic acid cholesteric liquid...
Antimicrobial resistance demands innovative molecular strategies to enhance antibiotic efficacy while minimizing the use of excipients. Building on the previously reported clarithromycin: ascorbic acid cholesteric liquid crystal, we present a new carrier-free system formed via the self-assembly of clarithromycin and N-acetylcysteine, capable of forming both a cholesteric liquid crystal and its corresponding xerogel. The system exhibited intense birefringence and characteristic optical textures, confirming the formation of an ordered mesophase sensitive to temperature and N-acetylcysteine concentration. Rheological studies revealed viscoelastic solid-like behaviour, while powder X-ray diffraction and scanning electron microscopy of the xerogel evidenced a lamellar organization with an enhanced degree of crystalline order. Fourier transform infrared spectroscopy and nuclear magnetic resonance studies indicated the formation of a new salt stabilized through ionic interactions and hydrogen bonding. The cholesteric liquid crystal enhanced the antimicrobial and antibiofilm activity of clarithromycin against Staphylococcus aureus and, together with the mucolytic properties of N-acetylcysteine, positions it as a promising candidate for application in cystic fibrosis. These results establish self-assembled clarithromycin liquid crystals as a new generation of carrier-free antibiotics.
Development of long-acting intramuscular vortioxetine pamoate suspensions: Formulation optimization and pharmacokinetic evaluation.
Li Y, Wang T, Liu M … +3 more , Jia Y, Zhou F, Liang M
Eur J Pharm Biopharm · 2026 May · PMID 41720199 · Publisher ↗
This study aims to develop a long-acting intramuscular vortioxetine pamoate (VTXP) suspensions and evaluate their pharmacokinetic profiles. VTXP suspensions stabilized by Tween 20, Soluplus and poloxamer were prepared us...
This study aims to develop a long-acting intramuscular vortioxetine pamoate (VTXP) suspensions and evaluate their pharmacokinetic profiles. VTXP suspensions stabilized by Tween 20, Soluplus and poloxamer were prepared using Planetary Ball Mill at lab-scale to identify an optimal stabilizer. Pilot-scale batches were then evaluated by varying drug loading, bead quantity, and bead size to optimize milling pressure and cycle. The VTXP suspensions were characterized by laser diffraction (LD) for particle size analysis, viscosity measurement, injection force tests, X-ray Powder Diffraction (XRPD) for solid-state measurement and in vitro release. Pharmacokinetic (PK) studies were conducted in rats and dogs, comparing the formulations with different particle sizes by oral and IM administration. 15% VTXP stabilized by 3% poloxamer 338 suspensions exhibited optimal injection properties: suitable viscosity (10-13cP) and moderate injection force (8-24 N). All VTXP suspensions had similar overall release profiles, minor differences were observed in their drug release behavior within the first 2 h. 2.5 µm VTXP suspension had extended t (rat 188 h, dog 39.6 h) by intramuscular (IM) administration, compared to t1/2 (rat 2.8 h, dog 8.3 h) via intragastric Route (IG) administration. Additionally, lower burst releases were confirmed (rat 10.2%, dog 3.8%) by the animal test. This study confirms that the VTXP suspension achieves long-acting performance and low burst release for IM administration.
Magnetic immunoprecipitation assay for the isolation of adalimumab and degradation products in preclinical biological samples.
Abdelaziz MM, Zhang Y, Ballesteros ME … +9 more , Groer C, Richards DS, Gong H, Bruin G, Dimke T, Koepke S, Bechtold-Peters K, Schöneich C, Laird Forrest M
Eur J Pharm Biopharm · 2026 May · PMID 41713624 · Publisher ↗
Evaluation of pharmacokinetics is a cornerstone in the developability assessment of therapeutic monoclonal antibodies (mAbs). For accurate evaluation of mAbs' concentration-time profile, administered mAbs should be isola...
Evaluation of pharmacokinetics is a cornerstone in the developability assessment of therapeutic monoclonal antibodies (mAbs). For accurate evaluation of mAbs' concentration-time profile, administered mAbs should be isolated from the interfering host proteins in serum samples. While there are multiple approaches to purify and quantify the administered mAb, they are limited by drawbacks such as low specificity, relatively-large plasma volume requirements, and tedious procedures for sample preparation and analysis. Here, we present an immunoprecipitation assay that uses a highly specific anti-human IgG1 antibody coupled with magnetic beads (R10-coupled Dynabeads) for the purification of adalimumab and forced-oxidized variants. The specificity and binding capacity of R10-coupled Dynabeads were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. To demonstrate the wide applicability of this method, two different stressed variants involving mixtures with rat proteins were examined which are chemical oxidation stress and physical agitation stress. The results showed comparable recovery of native adalimumab and oxidized variants from in vitro and in vivo rat proteins mixture. R10-coupled Dynabeads also recovered aggregated species, but the method itself induced more aggregate formation as evident from analysis by dynamic light scattering and background membrane imaging. Pharmacokinetic evaluation showed a typical concentration-time profile for native adalimumab which is broadly consistent with reported profiles. This method can provide an efficient and highly-specific recovery of human IgG1 and degradation products from preclinical biological samples, provided that the epitope recognized by the used anti-human IgG antibody is retained and accessible. Furthermore, the integration of R10-coupled Dynabeads purification, Trypsin/Lys-C digestion, and QToF LC-MS/MS analysis enabled efficient capture of the oxidized species generated by AAPH and HO (% sequence coverage ≥ 90%). Accordingly, this combined workflow can be applied to study in vivo modifications of therapeutic proteins (e.g. oxidation, deamidation) after exposure to an anatomical environment.
Functionalized chitosan-based mucoadhesive buccal films for the local delivery of triamcinolone acetonide to the oral mucosa in anti-inflammatory therapy.
Samprasit W, Chamsai B, Sinsuebpol C … +3 more , Sahatsapan N, Patrojanasophon P, Opanasopit P
Eur J Pharm Biopharm · 2026 May · PMID 41702537 · Publisher ↗
Mucoadhesion to the oral tissue is a major challenge in the local delivery of anti-inflammatory drugs. Therefore, this study developed and evaluated mucoadhesive buccal films based on chitosan (CS) and its functionalized...
Mucoadhesion to the oral tissue is a major challenge in the local delivery of anti-inflammatory drugs. Therefore, this study developed and evaluated mucoadhesive buccal films based on chitosan (CS) and its functionalized derivatives, including cysteine-functionalized CS (C-CS) and maleimide-functionalized CS (M-CS), for the local delivery of triamcinolone acetonide (TA). Films were prepared by the solvent casting method and characterized for physicochemical and mechanical properties, including weight, thickness, morphology, tensile strength, Young's modulus, and chemical properties. Mucoadhesive performance was assessed by wetting time, swelling, mucin interaction, and mucoadhesive force. TA content, release, and buccal deposition were evaluated for delivery efficiency. Cell-based assays were conducted to evaluate cytotoxicity, anti-inflammatory activity, and cell migration, with the results compared to those of commercial TA oral pastes. In vivo studies were performed to assess mucoadhesion, acceptability, and irritation potential. Results showed that CS and its derivatives were successfully incorporated into TA films with suitable physicochemical properties. Although tensile strength, Young's modulus, and surface morphology were slightly changed, mucoadhesion significantly improved, particularly with M-CS. All films released TA rapidly, with films containing C-CS and M-CS exhibiting significantly higher TA buccal deposition. TA films demonstrated anti-inflammatory activity without cytotoxicity and with a lower effect on cell migration than commercial pastes, especially with M-CS. Furthermore, CS and its derivatives, especially M-CS, provided prolonged mucoadhesion, with over 50% of participants satisfied and no buccal irritation after 24 h. These findings support functionalized CS-based mucoadhesive films as potential platforms for local delivery of TA to the oral mucosa in anti-inflammatory therapy.
Advances in metal-organic framework-based drug delivery system in cuproptosis-mediated cancer therapy.
Ruan H, Chen Y, Qian J … +8 more , Ma X, Xu Y, Deng Y, Pan Y, Kushwaha A, Kumar A, Zheng B, Liu J
Eur J Pharm Biopharm · 2026 May · PMID 41692172 · Publisher ↗
Cancer continues to pose an immense burden on global health, ranking among the foremost causes of disease-associated mortality. Conventional diagnostic platforms for tumor biomarkers, while widely adopted, remain constra...
Cancer continues to pose an immense burden on global health, ranking among the foremost causes of disease-associated mortality. Conventional diagnostic platforms for tumor biomarkers, while widely adopted, remain constrained by limited sensitivity, protracted workflows, and substantial economic costs, thereby restricting their clinical applicability. Therapeutic modalities such as chemotherapy and radiotherapy further compound the challenge, offering only modest selectivity and being accompanied by significant systemic toxicity and a high likelihood of relapse. Metal-organic frameworks (MOFs) represent a class of structurally tailorable nanomaterials composed of modular building units, featuring tunable porosity and favourable biocompatibility, which together provide an efficient platform for drug encapsulation and controlled release. Their tumour accumulation behaviour is strongly governed by key physicochemical parameters, including particle size, morphology, and surface chemistry. Pristine MOFs primarily rely on passive tumour targeting through the enhanced permeability and retention effect, whereas surface functionalization with targeting ligands can markedly improve tumor selective enrichment and cellular uptake. Consequently, the therapeutic delivery performance of MOFs must be critically assessed in relation to their specific structural design and surface engineering strategies. In parallel, the identification of cuproptosis, a mitochondria-centered copper-dependent mode of regulated cell death, has opened a distinct mechanistic avenue for oncological intervention. This process arises from the aberrant interaction of copper ions with lipoylated tricarboxylic acid cycle proteins, culminating in excessive protein acylation, destabilization of Fe-S cluster enzymes, proteotoxic stress, and mitochondrial collapse. The rapid evolution of pharmacological agents exploiting this pathway underscores its transformative therapeutic potential. This review critically consolidates recent progress at the interface of MOFs and cuproptosis, emphasizing design strategies, mechanistic insights, and therapeutic deployment, while also addressing unresolved issues in pharmacokinetics, biosafety, and translational feasibility that must be overcome for clinical realization.
KDEL-mediated modulation of intracellular trafficking in cell-targeted protein drugs.
Voltà-Durán E, Alba-Castellon L, Arena LA … +6 more , Sánchez JM, Casanova I, Mangues R, Villaverde A, Vázquez E, Unzueta U
Eur J Pharm Biopharm · 2026 May · PMID 41690333 · Publisher ↗
The biological activity of therapeutic proteins, upon intracellular delivery, is dramatically minimized by lysosomal proteolytic digestion. This is a limitation when developing cell-targeted pharmaceuticals that penetrat...
The biological activity of therapeutic proteins, upon intracellular delivery, is dramatically minimized by lysosomal proteolytic digestion. This is a limitation when developing cell-targeted pharmaceuticals that penetrate target cells via receptor recognition and endosomal engulfment. Since proteins benefit from functional and conformational versatility, editable by genetic engineering, endosomolytic protein domains are often fused to the functional polypeptide to promote their cytosolic delivery, aiming at minimizing proteolysis in mature lysosomes. This straightforward strategy has, however, rendered irregular results, linked to the fusogenic nature of most of the tested domains. Alternatively, proteolysis of protein drugs might be controlled by bypassing the lysosomal route, forcing an unconventional traffic of the uptaken protein material to be secreted from the endoplasmic reticulum (ER). This possibility, used in nature by several plant and microbial proteins, has been evaluated here by functionalizing a protein-only antitumoral drug, based on a cell-targeted diphtheria toxin, with a C-terminal KDEL motif. Thus, if KDEL were able to reprogram the intracellular trafficking, KDEL-tagged cell delivered proteins would be expected to avoid the lysosomal degradation, resulting in enhanced stability and activity. The obtained results validate this hypothesis and point out KDEL as a promising functional agent in cell-targeted protein drugs.
Atypical gelation of Elagolix sodium in aqueous media: Mechanistic insights and Inhibition via coamorphization.
Shi J, Shen P, Zhang X … +6 more , Su M, Tang M, Gao Y, Zhang J, Qian S, Wei Y
Eur J Pharm Biopharm · 2026 May · PMID 41690332 · Publisher ↗
Elagolix sodium (ELS), a non-peptide oral gonadotropin-releasing hormone receptor (GnRH) antagonist approved for the treatment of endometriosis-associated pain, displays atypical gelation in aqueous environments along wi...
Elagolix sodium (ELS), a non-peptide oral gonadotropin-releasing hormone receptor (GnRH) antagonist approved for the treatment of endometriosis-associated pain, displays atypical gelation in aqueous environments along with challenging physical properties such as high hygroscopicity. To address the formulation challenges posed by ELS gelation and high hygroscopicity, this study not only investigates the molecular mechanisms governing ELS gel formation but also evaluates co-amorphization with quercetin as a practical strategy to suppress gelation and enhance stability. Unlike conventional gelation mechanisms of small molecules, ELS was found to self-assemble into a metastable spherulitic gel network in aqueous media, where water molecules acted as critical "binders" for both initiation and stabilization. Comprehensive morphological, thermal, spectroscopic, and rheological analyses were employed to elucidate ELS gelation process. Polarized light microscopy (PLM) revealed that the hydrogel consists of transient spherulite domains, while Fourier Transform Infrared Spectroscopy (FTIR), Raman spectroscopy and Liquid-state H nuclear magnetic resonance spectroscopy (H NMR) demonstrated that gel formation is driven by a combination of dipole-dipole electrostatic interactions and π-π stacking between ELS molecules, along with intermolecular hydrogen bonding between ELS and water. Rheological studies further confirmed a temperature-dependent transition from fibrous structure to a densely cross-linked spherulitic network, indicating enhanced gel strength at lower gelation temperatures. Coamorphization of ELS with quercetin (QUE) not only completely inhibits gelation but also significantly reduces the hygroscopicity of ELS. Overall, this study provides fundamental insights into the mechanism of atypical small-molecule gelation while offering a practical strategy to overcome gelation challenges in the formulation and processing of ELS-based pharmaceuticals.
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