European Journal Of Pharmaceutics And Biopharmaceutics[JOURNAL]
Sun
200 papers
In vivo pharmacokinetic and toxicity evaluation of Andrographis paniculata extract-loaded self-microemulsifying drug delivery system.
Pornpitchanarong C, Jaewjira S, Taesotikul T … +2 more , Opanasopit P, Patrojanasophon P
Eur J Pharm Biopharm · 2026 Aug · PMID 42119863 · Publisher ↗
This study aimed to conduct a comprehensive in vivo assessment of a novel Andrographis paniculata (AP) extract-loaded self-microemulsifying drug delivery system (AP-SMEDDS), focusing on enhancing the oral bioavailability...
This study aimed to conduct a comprehensive in vivo assessment of a novel Andrographis paniculata (AP) extract-loaded self-microemulsifying drug delivery system (AP-SMEDDS), focusing on enhancing the oral bioavailability of andrographolide (AN) and establishing its preclinical safety profile. A comparative pharmacokinetic study was performed in rats to evaluate AP-SMEDDS against a conventional AP powder suspension. Concurrently, a 28-day repeated-dose oral toxicity study was conducted in Sprague Dawley rats at doses up to 31 mg/kg/day, followed by a 14-day recovery period to assess the reversibility of potential toxic effects. Pharmacokinetic analysis revealed that the SMEDDS formulation significantly optimized AN absorption, achieving a 4.3-fold higher maximum plasma concentration (C) and a 1.3-fold increase in total systemic exposure (AUC) compared to the powder suspension. This enhancement was possibly attributed to the pre-solubilized state of AN within nano-sized droplets, which bypasses dissolution rate-limited absorption. The toxicity study established a no-observed-adverse-effect level of 31 mg/kg/day, with no treatment-related mortality, adverse clinical signs, or histopathological lesions observed in vital organs. The AP-SMEDDS effectively overcame the bioavailability constraints of traditional AP extracts while maintaining a promising safety profile. These findings provided robust preclinical evidence to support the clinical translation of this phytopharmaceutical formulation.
Cholesterol-butyl-biguanide conjugate as a novel excipient enhances the efficacy of doxorubicin liposomes against triple-negative breast cancer by potentiating immunogenic cell death.
Wang Y, Li L, Fan Y … +2 more , Zheng J, Liu H
Eur J Pharm Biopharm · 2026 Aug · PMID 42106126 · Publisher ↗
Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options and poor prognosis. Although doxorubicin (DOX)-loaded liposomes are clinically used, their tumor-targeting efficiency and...
Triple-negative breast cancer (TNBC) is an aggressive malignancy with limited therapeutic options and poor prognosis. Although doxorubicin (DOX)-loaded liposomes are clinically used, their tumor-targeting efficiency and overall therapeutic efficacy remain suboptimal. To overcome these limitations, we designed and synthesized a novel cationic lipid excipient, cholesterol-butyl-biguanide (CBB), and formulated DOX-loaded CBB liposomes (Lip CBB@DOX) via active loading. Physicochemical characterization confirmed well-defined vesicular morphology, a positive surface charge, and pH-responsive drug release. In vitro, Lip CBB@DOX markedly increased DOX uptake by 4T1 cells, leading to enhanced cytotoxicity, reduced migration and proliferation, and elevated apoptosis. Mechanistic studies showed that Lip CBB@DOX potentiated DOX-induced immunogenic cell death, as indicated by increased calreticulin exposure and HMGB1 release. In a 4T1 murine model, Lip CBB@DOX produced the greatest tumor growth inhibition without aggravating systemic toxicity; histology revealed reduced tumor-associated extramedullary hematopoiesis and extensive tumor necrosis. Collectively, these results indicate that CBB is a safe and effective liposomal excipient that enhances DOX delivery and amplifies ICD-mediated antitumor immunity, offering a promising strategy to improve TNBC therapy and informing future optimization of biguanide-modified liposomal carriers.
Development of levothyroxine sodium pediatric oral solution driven by STEP database: Stability study and degradation products by LC-MS.
Camboim BL, Bersagui BS, de Oliveira Almeida SH … +3 more , Ayres MV, Loureiro Mendez AS, Garcia CV
Eur J Pharm Biopharm · 2026 Jul · PMID 42097333 · Publisher ↗
Levothyroxine sodium (SLT4) is the sodium salt of the thyroid hormone thyroxine, being the first-choice replacement therapy in hypothyroid disease. Congenital hypothyroidism affects infants, and represents one of the mos...
Levothyroxine sodium (SLT4) is the sodium salt of the thyroid hormone thyroxine, being the first-choice replacement therapy in hypothyroid disease. Congenital hypothyroidism affects infants, and represents one of the most common preventable causes of intellectual disability worldwide. In Brazil and other countries, tablets are the only dosage form of SLT4 for oral use. Pediatric patients and adults unable to swallow require SLT4 extemporaneously prepared in the hospital's routine, which can compromise safety. On the other hand, oral SLT4 solutions are available in USA, Italy, Spain, and United Kingdom. The aim of this work was to develop a SLT4 oral liquid formulation and assess its stability during 63 days under 4 °C, 25 °C and 40 °C, comparing amber glass bottles and sachet packing. In the development stage, excipients were evaluated by data tools (STEP and PERA) and the most suitable for pediatric use were chosen. An HPLC method was developed and validated to analyze SLT4 content, and forced degradation outcomes were investigated through UPLC-MS. Every 7 days, pH, drug amount, visual aspect, organoleptic properties and microbiological content were analyzed. The SLT4 30 µg/mL oral solution showed adequate physical chemical and microbiological characteristics. It was stable for 63 days when stored both in sachet and amber glass bottles at 4 °C and 25 °C. Six major degradation products structures were proposed after stress testing evaluations. It was possible to obtain a simple STL4 oral solution, with pediatric-safe excipients and dosing flexibility, representing an alternative for hospital treatment of hypothyroidism.
Decoupling efficacy from toxicity: Inhalable liposomal nintedanib for safe and effective treatment of pulmonary fibrosis.
Mu X, Zeng C, Liu H … +9 more , Sun X, Cao Y, Wu M, Yin T, Su Y, Zhao J, Wu T, Ji M, Zhang Y
Eur J Pharm Biopharm · 2026 Jul · PMID 42092598 · Publisher ↗
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Nintedanib (NDNB), a triple tyrosine kinase inhibitor, slows disease progression, but its clinical...
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease with limited treatment options. Nintedanib (NDNB), a triple tyrosine kinase inhibitor, slows disease progression, but its clinical utility is constrained by the oral formulation. This formulation suffers from low oral bioavailability and dose-limiting systemic toxicities, including severe gastrointestinal disturbances and hepatotoxicity. To overcome these challenges, we developed an inhalable nintedanib liposomal suspension (NDNB-Lip) for local pulmonary delivery. The optimized NDNB-Lip exhibited a uniform nanoscale size, high encapsulation efficiency, and sustained release profile in vitro. The results of the stress testing suggested that NDNB-Lip remained relatively stable under high temperature and intense light. Pharmacokinetic studies revealed that pulmonary inhalation of NDNB-Lip achieved a remarkable enhancement in lung-targeted exposure, with a relative bioavailability in lung tissue. In a bleomycin-induced pulmonary fibrosis model, NDNB-Lip demonstrated superior anti-fibrotic efficacy, significantly attenuating histological damage and reducing key fibrotic markers. Crucially, this enhanced efficacy was coupled with a markedly improved safety profile, as inhaled NDNB-Lip effectively circumvented the gastrointestinal and hepatic injuries associated with oral administration. Our findings underscore inhaled NDNB-Lip as a promising therapeutic strategy that decouples efficacy from toxicity, offering a novel paradigm for the safe and effective long-term management of IPF.
Core-shell electrospun fibers for enhanced dissolution and stability of amorphous empagliflozin.
Saršūns K, Anspoka N, Stivriņa D … +6 more , Kons A, Zabolotnii V, Bērziņš K, Meija R, Viter R, Bērziņš A
Eur J Pharm Biopharm · 2026 Jul · PMID 42081952 · Publisher ↗
Core-shell electrospun fibers represent a promising platform for formulating poorly water-soluble drugs as amorphous solid dispersions with enhanced dissolution and physical stability. This study developed and characteri...
Core-shell electrospun fibers represent a promising platform for formulating poorly water-soluble drugs as amorphous solid dispersions with enhanced dissolution and physical stability. This study developed and characterized coaxial electrospun fibers containing the antidiabetic drug empagliflozin (EMPA) with drug loadings up to 22% w/w, using a Soluplus-EMPA core and Kollicoat Smartseal shell architecture. Comprehensive solid-state characterization confirmed complete amorphization across all compositions and intimate molecular-level mixing stabilized by drug-polymer hydrogen bonding. Raman microscopy mapping verified the intended core-shell structure with spatial separation of drug-rich core from polymer shell. Systematic comparison against film-cast amorphous solid dispersions and physical mixtures of identical composition (18% w/w) confirmed faster dissolution and higher drug release performance of the electrospun fibers. Under accelerated stability conditions (3 months at 40°C/75% RH) the electrospun fibers showed the same stability as the film-cast formulation, in contrast to the physical mixture crystallizing within one week. Notably, dynamic vapor sorption analysis revealed that electrospun fibers absorbed less moisture than film-cast ASD despite their higher surface area and porous structure, attributed to the protective barrier function of the Kollicoat shell. These findings establish core-shell electrospun fibers as an advantageous platform combining rapid dissolution with moisture-resistant stability for empagliflozin formulation.
Computational and machine learning approach for nanoparticles-enhanced bio-heat transport with coupled effects of interparticle spacing and particles radius.
Darvesh A, Collantes Santisteban LJ, El-Rahman MA … +2 more , Khan S, El-Wahed Khalifa HA
Eur J Pharm Biopharm · 2026 Jul · PMID 42069266 · Publisher ↗
Targeted delivery of drugs and hyperthermia in cardiovascular disease demand the accurate delivery of nanoparticles in complex arterial geometries. This paper introduces combined hybrid computational model that concomita...
Targeted delivery of drugs and hyperthermia in cardiovascular disease demand the accurate delivery of nanoparticles in complex arterial geometries. This paper introduces combined hybrid computational model that concomitantly examines the combined impact of nanoparticle radius and interparticle spacing on the thermal and mass transport characteristics of ternary bio-nanofluid flow under magnetohydrodynamic (MHD) effect. The ternary fluid is composed of blood fluid with suspended nanoparticles such as gold (Au), silver (Ag) silica SiO. The mathematical model accounts for geometric properties of nanoparticles such as nanoparticles radius and interparticle spacing for their practical utility for several medical interventions. The numerical analysis is based on hybrid computational strategy, where the solutions are determined through the bvp4c numerical solver and then a novel supervised multi hidden layers Artificial neural network (ANN) is integrated. The proposed model has a high predictive capability with an exceptionally high accuracy with the lowest Mean squared error and ideal regression coefficient MSE=9.6327×10, Gradient=9.5681e-08, Mu=1e-09, and R=1.0. Some of the main findings indicate that less spacing between particles (h=0.1) leads to continuous networks of thermal percolation, which enhance the thermal conductivity . to improve the efficiency of hyperthermia, whereas the larger nanoparticles radius .) offer a higher drug-loading capacity. .. Optimization of the magnetic parameter (.) also decreases flow velocity . and extends the nanoparticle residence time . which allows sustained drug delivery, results directly applicable to clinical-strength and . MRI-guided interventions. Radiation parameter . increases temperature of the ternary hybrid bio-nanofluids by . giving controllable thermal modulation to applications of hyperthermia. . The purpose of such an integrated computational-machine learning systems is to provide a better pathway, which could be crucial in several bio-medical interventions. The results can be used to offer practical advice to stent manufactures, interventional radiologist and pharmaceutical developers to create evidence-based cardiovascular therapy of the next generation.
Mechanistic insights into dissolution of highly drug-loaded amorphous solid dispersions of a fast-crystallising drug.
Kolisnyk T, Mohylyuk V
Eur J Pharm Biopharm · 2026 Jul · PMID 42069265 · Publisher ↗
The dissolution behaviour of fast-crystallising amorphous solid dispersions (ASDs) at drug loadings (DLs) far exceeding the amorphous solubility limit remains poorly understood. In this study, we investigate how extreme...
The dissolution behaviour of fast-crystallising amorphous solid dispersions (ASDs) at drug loadings (DLs) far exceeding the amorphous solubility limit remains poorly understood. In this study, we investigate how extreme DLs influence dissolution mechanisms in naproxen-copovidone VA64 ASDs prepared by hot-melt extrusion at 20, 50, and 70 wt% DL. Rapid post-extrusion cooling was applied at 70 wt% DL to kinetically suppress crystal growth, while lower DL formulations remained amorphous as confirmed by DSC and PXRD. Drug-polymer interactions were analysed using ATR-FTIR combined with principal component analysis. Saturation solubility measurements revealed moderate advantages of ASDs over physical mixtures, suggesting that polymer-mediated interfacial effects contribute to solubility enhancement independently of amorphisation. Non-sink dissolution testing revealed a non-monotonic, DL-dependent behaviour. At 20 wt% DL, naproxen remained amorphous for at least 2 h, enabling near-congruent drug-polymer release and the highest dissolution performance. At 50 wt% DL, rapid surface crystallisation within a dense swollen polymer layer restricted drug release. Unexpectedly, dissolution performance partially recovered at 70 wt% DL despite crystallization, as the reduced polymer fraction generated a more porous hydrated layer that facilitated liquid penetration and drug release compared with 50 wt% DL ASDs and physical mixtures. Spectroscopic analysis showed progressive loss of hydrogen bonding at intermediate and high DLs, while transient, non-specific drug-polymer associations persisted and likely contributed to improved wettability. These findings demonstrate that dissolution enhancement in fast-crystallising ASDs can be sustained above the amorphous solubility limit when the architecture of the hydrated layer - together with persistent non-specific drug-polymer interactions in aqueous media - governs drug transport rather than amorphous stability alone.
Co-processed excipients for DC: pharmaceutical applications, manufacturing techniques, and critical quality attributes.
Zhang M, Lin X, Hong Y … +2 more , Shen L, Zhao L
Eur J Pharm Biopharm · 2026 Jul · PMID 42067047 · Publisher ↗
The widespread adoption of direct compression has increased the performance requirements for pharmaceutical excipients. While single excipients often fail to meet these multifaceted demands, co-processed excipients integ...
The widespread adoption of direct compression has increased the performance requirements for pharmaceutical excipients. While single excipients often fail to meet these multifaceted demands, co-processed excipients integrate multiple components through specialized processes to create superior multifunctional systems, thereby emerging as a pivotal solution for advancing DC formulations. This review systematically summarizes recent advances in CPEs, outlining their applications in modulating drug release, improving compressibility, and enhancing compatibility with moisture-sensitive drugs. It further elucidates the structure-performance relationships of various manufacturing techniques and analyzes the decisive role of key material attributes in dictating product performance. This review aims to offer valuable theoretical guidance for the future development and application of high-performance CPEs.
Cationic nanolipoplexes for high-performance mRNA transfection at the nasal mucosa.
Dechbumroong P, Lapmanee S, Keaswejjareansuk W … +6 more , Yimsoo T, Treesuppharat W, Ariyachayut A, Liang XJ, Namdee K, Zhu M
Eur J Pharm Biopharm · 2026 Jul · PMID 42044858 · Publisher ↗
Intranasal mRNA therapeutic design represents a compelling strategy by offering a minimally invasive delivery route that concentrates mRNA activity at the nasal mucosa, promotes localized biological responses, and limits...
Intranasal mRNA therapeutic design represents a compelling strategy by offering a minimally invasive delivery route that concentrates mRNA activity at the nasal mucosa, promotes localized biological responses, and limits systemic distribution and first-pass metabolism. However, biological barriers such as the mucus layer remain significant obstacles to effective delivery. In this study, we developed an intranasal mRNA delivery platform based on non-PEGylated cationic liposomes composed of SPC, DPPC, cholesterol, and DDAB, fabricated using a microfluidic approach. Among the tested formulations, B4 lipoplexes (SPC, DPPC, cholesterol, and DDAB at a 2:3:1:0.5 M ratio) demonstrated desired properties, including a positive surface charge of +21.0 mV, a particle size of 140 nm, a low polydispersity (0.28), and as high as 84% mRNA encapsulation. The lipoplexes were systematically evaluated for physicochemical characteristics, mucoadhesiveness, mucus penetration, in vitro cell viability and uptake, and transfection efficiency both in vitro and in vivo. The formulation demonstrated strong mucoadhesive behavior while maintaining efficient mucus penetration. Fluorescence imaging confirmed robust cellular uptake and successful cytosolic mRNA delivery, resulting in high transfection efficiency. Notably, the lipoplexes encapsulating GFP and SARS-CoV-2 Omicron spike protein mRNA achieved efficient in vitro transfection with minimal cytotoxicity in A549 and HEK293T cells, as confirmed by MTT assay. Importantly, the lipoplexes containing 0.25-2 µg mRNA did not trigger significant pro-inflammatory cytokine responses (IL-1β, IL-6, TNF-α, and MCP-1) in THP-1 cells. Following intranasal administration in C57BL/6 mice, firefly luciferase mRNA-loaded B4 lipoplexes exhibited efficient adhesion to and penetration through nasal mucus, facilitated transfection of cells lining the nasal cavity, and produced localized reporter protein expression without detectable off-target expression. Collectively, these findings highlighted the strong potential of the non-PEGylated cationic lipoplexes as a safe and effective intranasal mRNA delivery platform, offering a noninvasive targeting strategy that broadens the applicability of lipid-based mRNA therapeutics.
Spatiotemporally controlled systemic delivery reshapes the in vivo fate of a cationic antimicrobial peptide for lung-selective exposure and an improved therapeutic index.
Tao W, Li M, Zhou Y … +4 more , Liu K, Wu G, Guo J, Di B
Eur J Pharm Biopharm · 2026 Jul · PMID 42044857 · Publisher ↗
A key biopharmaceutic barrier in systemic treatment of pulmonary infections is achieving sufficient drug exposure at infected lung sites with cationic antimicrobial peptides (AMPs), which are prone to proteolytic degrada...
A key biopharmaceutic barrier in systemic treatment of pulmonary infections is achieving sufficient drug exposure at infected lung sites with cationic antimicrobial peptides (AMPs), which are prone to proteolytic degradation, rapid clearance, and off-target interactions in circulation. S-thanatin (Ts) is a cationic AMP with potent in vitro antibacterial activity and low resistance liability, yet its unfavorable in vivo fate limits therapeutic efficacy. To address this limitation, we implemented a spatiotemporally controlled systemic delivery strategy that couples pathogen-associated localization with enzyme-activated, on-site release. As a practical formulation to realize this concept, Ts@CPN@PM was electrostatically assembled with bacteria-pre-stimulated macrophage membranes for pathogen-associated targeting and equipped with a matrix metalloproteinase-3 (MMP-3)-cleavable NFF-3 switch for infection-microenvironment-triggered release. Ts@CPN@PM achieved ∼95 % in vitro Ts release under elevated MMP-3 conditions and preferentially accumulated in infected lungs (>70 % by fluorescence quantification). In an antibiotic-resistant E. coli pneumonia model, Ts@CPN@PM improved survival (10 % to 60 %), reduced pulmonary bacterial burden (∼2 log CFU/g), and attenuated inflammatory responses. Ts@CPN@PM showed favorable cytocompatibility and hemocompatibility in vitro, and systemic biosafety was confirmed in healthy mice. Overall, these findings support spatiotemporal control of lung-site exposure as a feasible route to improve the in vivo fate and therapeutic index of cationic AMPs for pulmonary bacterial infections.
AI/ML in drug product development & manufacturing - report on the 8th APV Winter conference.
Page S, Funke A, Juhnke M
Eur J Pharm Biopharm · 2026 Jul · PMID 42025883 · Publisher ↗
Artificial Intelligence and Machine Learning (AI/ML) have already revolutionized Drug Discovery. However, Chemistry, Manufacturing, and Controls (CMC) remains in "digital infancy". This report from the 8th APV Winter Con...
Artificial Intelligence and Machine Learning (AI/ML) have already revolutionized Drug Discovery. However, Chemistry, Manufacturing, and Controls (CMC) remains in "digital infancy". This report from the 8th APV Winter Conference with 55 participants details a critical industry shift toward Digital Design and Quantitative Formulation. Five cooperative shifts are necessary for this transformation: redefining scientists as orchestrators, democratizing computational fluency, prioritizing structured data, optimizing strategic experimentation, and aligning with evolving regulatory frameworks. Critical challenges like data reliability, model explainability, and "human-in-the-loop" accountability are addressed. Through case studies ranging from physicochemical profiling, formulation and process development, equipment design, manufacturing and analytical control, and biopharmaceutics, the conference demonstrated how AI/ML creates high-fidelity and interoperable architectures advancing drug product development and manufacturing.
Incorporation of micronized poorly soluble drug into orodispersible tablets by aqueous fluid bed granulation of co-processed excipients.
Badawi S, Lillotte T, Esser E … +3 more , Nueboldt C, Hoheisel W, Breitkreutz J
Eur J Pharm Biopharm · 2026 Jul · PMID 42013942 · Publisher ↗
The layering of active pharmaceutical ingredient (API) suspension on inert carriers through fluid bed granulation has been tackled in several studies. This study investigates the feasibility and impact of aqueous fluid b...
The layering of active pharmaceutical ingredient (API) suspension on inert carriers through fluid bed granulation has been tackled in several studies. This study investigates the feasibility and impact of aqueous fluid bed granulation of a poorly soluble micronized API suspension directly onto co-processed excipients as active carriers for orally dispersible tablet production. Indomethacin was selected as model API and Parteck ODT® (mannitol based) and StarLac® (lactose-based) were examined as carrier materials. Produced batches were systematically characterized for change in particle size distribution using laser diffraction, flow properties via Hausner ratio determination and morphology using scanning electron microscopy. The solid-state properties were evaluated using differential scanning calorimetry and XRPD, and moisture uptake was assessed via dynamic vapour sorption. The initial exposure of the carriers to water induced distinct morphological changes; controlled wetting of Parteck ODT® resulted in particle shrinkage due to surface-confined transient dissolution and subsequent recrystallisation of the mannitol outer layer. On the other hand, wetting the StarLac® caused extensive morphological collapse of it's spherical structure accompanied with a decrease in all the percentiles of the particle size distribution. Subsequent polymeric processing with hydroxypropyl methyl cellulose solution promoted particle growth and agglomeration for both carriers. Incremental Indomethacin addition further altered the surface, inducing progressive increase in surface roughness, which correlated with diminishing of packing efficiency observed in increase in Hausner ratio, yet all batches remained within passable limits. These findings demonstrate that while aqueous fluid bed layering is a feasible strategy for the solidification of micronized drug suspension onto co-processed excipients, the properties of the product inevitably depend on the inherent properties of the carrier material.
New insights into the intrinsic tryptophan fluorescence emission spectra of IgG antibodies and the impact of protein unfolding and aggregation.
Brack L, Binder J, Gialdini I … +4 more , Lamb DC, Friess W, Merkel OM, Schroeder R
Eur J Pharm Biopharm · 2026 Jul · PMID 42009236 · Publisher ↗
Intrinsic tryptophan (Trp) fluorescence emission (ITFE) spectroscopy is widely used in biologics development, yet interpretation remains challenging for proteins with more than one Trp, such as antibodies, and is often l...
Intrinsic tryptophan (Trp) fluorescence emission (ITFE) spectroscopy is widely used in biologics development, yet interpretation remains challenging for proteins with more than one Trp, such as antibodies, and is often limited to bulk spectral shifts. For better understanding and more detailed characterization of mAbs by ITFE, we analyzed an in-house therapeutic IgG1 (mAbT) and the National Institute of Standards and Technology (NIST mAb) reference IgG1. Human serum albumin (HSA) was used as a single-Trp protein control. Steady-state, second-derivative and time-resolved fluorescence measurements combined with Molecular Dynamics simulations enabled site-resolved interpretation of ITFE signals. A limited number of dominant Trp residues, primarily near the complementary-determining regions (CDRs) in the VH domains, were identified as the main contributors to the overall emission. Long fluorescence lifetimes (>5 ns) correlated with moderate solvent accessibility (around 25%) and low quenching propensity. The direction of spectral shifts during unfolding and aggregation was governed by the environment of the individual VH domain Trp. The increase in fluorescence intensity during denaturation was primarily attributed to unfolding and was further enhanced by thermal stress induced aggregation. Protein aggregation induced by interfacial stress produced similar spectral signatures in mAbT and HSA, indicating comparable effects on ITFE. This study demonstrates that integration of ITFE with molecular dynamic simulations allows for mechanistic interpretation beyond just an empirical description. By thoroughly interpreting ITFE spectra, one can obtain information about spectral properties of variable Trps residues in IgG1 molecules and gain valuable insights into protein denaturation mechanisms.
A biomimetic nanoparticle for the treatment of sepsis via anti-inflammatory, antioxidant, and anticoagulant mechanisms.
Xie H, Cao Y, He H … +3 more , Zheng B, Chen M, Ying Y
Eur J Pharm Biopharm · 2026 Jun · PMID 41990977 · Publisher ↗
Sepsis is a life-threatening syndrome resulting from a dysregulated immune response to infection, characterized by high morbidity and mortality. Excessive oxidative stress, inflammatory cytokine storms, and hyperactivate...
Sepsis is a life-threatening syndrome resulting from a dysregulated immune response to infection, characterized by high morbidity and mortality. Excessive oxidative stress, inflammatory cytokine storms, and hyperactivated coagulation cascades collectively drive multiple organ dysfunction, posing major challenges in clinical treatment. Quercetin (Que), a natural flavonoid with anti-inflammatory, antioxidant, and anticoagulant activities, has shown considerable potential as a therapeutic agent for sepsis. Nevertheless, its clinical translation is limited by poor aqueous solubility, chemical instability, and low bioavailability. To overcome these limitations, we designed a biomimetic nanoplatform based on mesoporous polydopamine (mPDA) nanoparticles for the efficient delivery of Que. Furthermore, to enhance the biocompatibility, circulation time, and inflammation-targeting capability, the Que-loaded mPDA nanoparticles were coated with platelet membranes (PM), yielding mPDA-Que@PM nanoparticles. In vitro, mPDA-Que@PM exhibited efficient ROS scavenging, significantly suppressed LPS-induced secretion of TNF-α, IL-6, and IL-1β, and inhibited the TLR4/NF-κB signaling pathway. In a CLP-induced sepsis mouse model, treatment with mPDA-Que@PM alleviated hepatic and pulmonary inflammation and oxidative damage, reduced serum thrombin and thrombin-antithrombin complex levels, improved coagulation abnormalities, and significantly increased survival. Additionally, the mPDA-Que@PM demonstrated excellent hemocompatibility and biosafety. This study presents a multifunctional, platelet-mimicking nanomedicine capable of simultaneously modulating oxidative stress, inflammation, and coagulation imbalance, offering a promising strategy for precise and synergistic intervention in sepsis.
Improving oral bioavailability and tabletability of celecoxib by preparing its three cocrystals.
Liu J, Yin L, Yang W … +4 more , Qin Y, Yan C, Jiang B, Deng Y
Eur J Pharm Biopharm · 2026 Jun · PMID 41985790 · Publisher ↗
Celecoxib (Cel) has extremely poor aqueous solubility, low bioavailability, and unsatisfactory powder mechanical properties for its tablet formulation development. Three cocrystals of Cel with tartaric acid (Ta), cinnami...
Celecoxib (Cel) has extremely poor aqueous solubility, low bioavailability, and unsatisfactory powder mechanical properties for its tablet formulation development. Three cocrystals of Cel with tartaric acid (Ta), cinnamic acid (Ca), and salicylamide (Sal) were prepared to improve these properties of Cel and characterized by PXRD, DSC and FTIR. The cocrystals underwent comprehensive in vitro characterization, encompassing equilibrium solubility, dissolution, and tabletability profiling, followed by in vivo pharmacokinetic evaluation to assess bioavailability and pharmacodynamic performance. The results demonstrated significant improvements in pharmaceutical properties by preparing the cocrystals of Cel. The equilibrium solubility of the Cel-Ca cocrystal was 3.4 times of that of Cel, and the maximum dissolution of the Cel-Sal cocrystal was about 2.7 times of that of Cel. The tensile strengths of the cocrystals were greater than the critical tensile strength of 1.7 MPa for the formation of tablets, and the three cocrystals could be used for direct tabletting. In vivo pharmacokinetic studies showed that the cocrystals shortened the peak concentration time of oral absorption of Cel and significantly enhanced the relative bioavailability.
Design and application of a dissolution-permeation apparatus with scalable surface area and controllable hydrodynamic conditions at the membrane interface.
Zůza D, Pritts D, Klimša V … +2 more , Beránek J, Štěpánek F
Eur J Pharm Biopharm · 2026 Jun · PMID 41980673 · Publisher ↗
The evaluation of drug release from enabling formulations often requires a coupled measurement of dissolution and permeation processes. While dissolution testing alone is well established in pharmaceutical development, c...
The evaluation of drug release from enabling formulations often requires a coupled measurement of dissolution and permeation processes. While dissolution testing alone is well established in pharmaceutical development, coupled dissolution-permeation studies often face challenges due to limited permeation surface area and poor control over local hydrodynamic conditions that affect the thickness of the unstirred water layer at the membrane interface. This study presents adissolution-permeation device integrating a standard USP II dissolution vessel and a custom-built permeation module with a sandwich structure, offering a permeation area that is scalable by multiplication. The functionality of the apparatus was demonstrated using carboxyfluorescein and caffeine as model solutes permeating across polycarbonate and polyvinylidene fluoride membranes under varying hydrodynamic conditions. The results provide a clear dependence of the apparent permeability on the flow velocity at the membrane interface, indicating a significant influence of the unstirred water layer. Simultaneous dissolution-permeation experiments with tablet prototypes exhibiting immediate and sustained drug release demonstrated the ability of the device to capture dynamic permeation behaviour, revealing an initial non-steady permeation phase that transitions into pseudo steady-state conditions. It has been shown that the permeation flux can be increased by multiplication of the basic permeation module to increase the membrane area to 100 cm. The findings establish the apparatus as a platform suitable for dynamic in vitro dissolution-permeation experiments with a potential to support formulation development and provide data for in-vivo-in-vitro correlations.
Editorial for the special issue "Excipients".
Herbig M, Mäder K, Salar-Behzadi S
Eur J Pharm Biopharm · 2026 Jun · PMID 41962854 · Publisher ↗
Abstract loading — click title to view on PubMed.
[F]FDG interactions with human serum albumin: Binding and molecular modeling studies.
Trusova V, Malovytsia U, Kuznietsov P … +4 more , Yakymenko I, Gorbenko G, Kominia M, Elsinga PH
Eur J Pharm Biopharm · 2026 Jun · PMID 41956223 · Publisher ↗
Using a set of techniques, including radiometric binding assays, kinetic measurements, fluorescence displacement, and molecular modeling, the interaction of [F]FDG with human serum albumin (HSA) was characterized. [F]FDG...
Using a set of techniques, including radiometric binding assays, kinetic measurements, fluorescence displacement, and molecular modeling, the interaction of [F]FDG with human serum albumin (HSA) was characterized. [F]FDG was found to display weak, saturable binding to HSA, with a maximal bound fraction of ∼40% and an apparent dissociation constant of ∼43 µM in the presence of glucose physiological concentration. Equilibrium was reached within ∼30-35 min, which is consistent with rapid, reversible association. Binding saturated near ∼100 µM HSA, a concentration relevant to the lower range of serum albumin in hypoalbuminemic patients. Molecular docking and 100-ns molecular dynamics simulations indicated [F]FDG engagement at the Sudlow's site I, without perturbing albumin structure. Modest and concentration-dependent displacement of warfarin by cold analog 2-deoxy-D-glucose supported partial competition at this site. Collectively, the obtained results indicate that [F]FDG exists partly in a transient albumin-associated state rather than exclusively in a freely diffusible form. While modest in magnitude, this interaction may contribute to variability in blood-pool and liver background uptake in patients with altered albumin or glucose levels, and provides quantitative reference values to refine interpretation of PET imaging under diverse metabolic and nutritional states. Recognizing this albumin-associated fraction may help interpret subtle variations in liver and blood-pool reference regions, improving the reliability of SUV-based assessments in patients with low albumin or altered glucose metabolism.
Ondansetron-loaded magnetically targeted nanocarriers for anxiety: optimization, in vitro characterization, and in vivo evaluation in rats.
Tantawy N, Elsalhy S, Alsofany JM … +6 more , Saleh AM, Alshehri SM, Alqarni SS, El-Sayed EK, Ahmed AA, El Naggar EE
Eur J Pharm Biopharm · 2026 Jun · PMID 41956222 · Publisher ↗
This study investigated an intranasal nose-to-brain delivery strategy to repurpose ondansetron (OND) for anxiety management using PLGA nanoparticles co-loaded with superparamagnetic iron oxide nanoparticles (SPIONs) and...
This study investigated an intranasal nose-to-brain delivery strategy to repurpose ondansetron (OND) for anxiety management using PLGA nanoparticles co-loaded with superparamagnetic iron oxide nanoparticles (SPIONs) and incorporated into a Carbopol 940 mucoadhesive gel. Nanoparticles were optimized using an I-optimal experimental design evaluating PLGA concentration and surfactant type. The optimized SPION/OND-PLGA nanoparticles showed a small particle size (141.547 ± 1.31 nm), narrow size distribution (PDI = 0.235 ± 0.002), relatively high zeta potential (-34.307 ± 0.53 mV), and satisfactory encapsulation efficiency (42.09 ± 1.34%). The developed nanogel exhibited acceptable organoleptic properties, shear-thinning behavior, sustained drug release, and enhanced ex vivo nasal permeability, with OND permeation values of 996.96 ± 6.53 μg, 621.92 ± 7.54 μg, and 317.87 ± 2.88 μg per cm within 6 h for the nanogel,SPION/PLGA NPs and aqueous solution, respectively. In vivo behavioral studies (open field test and elevated plus maze) demonstrated significant anxiolytic activity in all OND-treated groups, with superior efficacy for the magnetically targeted nanogel. Neurochemical and biochemical analysis indicated a monoaminergic-dominant anxiolytic profile, increased BDNF expression, and improved oxidative stress status. Molecular docking revealed strong OND binding to 5-HT5A and 5-HT3A receptors. Overall, magnetic intranasal nanocarriers substantially enhanced the anxiolytic and neuroprotective efficacy of ondansetron.
Recombinant human hyaluronidase PH20 facilitates rapid subcutaneous infusion: two randomized, double-blind, self-controlled phase III clinical trials.
Ma H, Lu X, Xiu J … +12 more , Cao M, Li J, Qiao Y, Liu Y, Wang Z, Zhang L, Qian X, Zhang H, Tang H, Zhao N, Yu Y, Zhang L
Eur J Pharm Biopharm · 2026 Jun · PMID 41935547 · Publisher ↗
BACKGROUND: Hyaluronidases (HAase) increase tissue permeability by depolymerizing hyaluronan in the extracellular matrix. Consequently, the subcutaneous (SC) delivery of substantial volumes of fluids or biotherapeutics i...
BACKGROUND: Hyaluronidases (HAase) increase tissue permeability by depolymerizing hyaluronan in the extracellular matrix. Consequently, the subcutaneous (SC) delivery of substantial volumes of fluids or biotherapeutics is facilitated. Recombinant human hyaluronidase PH20 (rHuPH20) has been developed to overcome the allergic and immunologic risks associated with animal-derived HAase. However, standalone rHuPH20 products remain unavailable in China despite increasing clinical demand. METHODS: Two randomized, double-blind, self-controlled phase III clinical trials (phase IIIa and IIIb) were conducted to evaluate the SC infusion rate, tolerability and safety of KJ017, a rHuPH20, in healthy participants receiving gravity-driven SC infusion. The primary outcome was SC infusion rate. The secondary outcomes included arm circumference, time to recover baseline arm circumference, and safety evaluations, such as adverse events (AEs). RESULTS: Across both trials, SC infusion rates in all KJ017 groups (128/150 IU, 385 IU, and 1540/1500 IU) were significantly higher than those in the placebo groups (all P < 0.001). KJ017 administration was associated with minimal increases in limb circumference at the infusion site, suggesting reduced local fluid accumulation and more efficient tissue dispersion of the infused solution. SC administration of KJ017 across a dose range of 128 IU to 1540 IU was well tolerated and safe, and no allergic reactions were documented. CONCLUSIONS: These phase III trials demonstrate that KJ017 effectively enhances gravity-driven SC infusion performance while maintaining favorable safety and tolerability. By increasing SC tissue permeability, KJ017 enables the delivery of clinically relevant fluid volumes through the SC route across multiple anatomical sites. These findings support the further development of KJ017 as an enabling agent for large-volume SC administration and for potential co-administration with therapeutic agents requiring rapid or high-volume SC delivery. Trial registrationChictr.org.cn, ChiCTR2100049727 and ClinicalTrials.gov, NCT06604546.
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