European Journal Of Pharmaceutics And Biopharmaceutics[JOURNAL]
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200 papers
Corrigendum to "DNA vaccination for cervical cancer: Strategic optimisation of RALA mediated gene delivery from a biodegradable microneedle system" [Eur. J. Pharm. Biopharm. 127 (2018) 288-297].
Cole G, Ali AA, McCrudden CM … +7 more , McBride JW, McCaffrey J, Robson T, Kett VL, Dunne NJ, Donnelly RF, McCarthy HO
Eur J Pharm Biopharm · 2026 May · PMID 41688300 · Publisher ↗
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Corrigendum to "A triple crosslinked micelle-hydrogel lacrimal implant for localized and prolonged therapy of glaucoma" [Eur. J. Pharm. Biopharm. 185 (2023) 44-54].
Zhao J, Xiong J, Ning Y … +8 more , Zhao J, Wang Z, Long L, He H, Gou J, Yin T, Tang X, Zhang Y
Eur J Pharm Biopharm · 2026 May · PMID 41680012 · Publisher ↗
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Site-specific targeting in immunoliposomal nanomedicine for oncology: opportunities and limitations.
Milczarek M, Kleczkowska P
Eur J Pharm Biopharm · 2026 May · PMID 41655818 · Publisher ↗
The integration of monoclonal antibodies with liposomal nanocarriers has opened new possibilities in targeted cancer therapy. Immunoliposomes, which are liposomes surface-conjugated with antibodies or antibody fragments,...
The integration of monoclonal antibodies with liposomal nanocarriers has opened new possibilities in targeted cancer therapy. Immunoliposomes, which are liposomes surface-conjugated with antibodies or antibody fragments, offer dual specificity by combining passive targeting (via the enhanced permeability and retention effect) with active targeting of tumor-specific antigens. This design allows for increased drug accumulation in tumor tissue and reduced off-target toxicity, which are critical challenges in conventional chemotherapy. Although no immunoliposomal therapy has yet received the FDA or EMA approval, the platform continues to evolve. Several formulations are under clinical investigation for various solid tumors, including triple-negative breast cancer, glioblastoma, and non-small cell lung cancer. For example, in a phase II study of anti-EGFR immunoliposomes loaded with doxorubicin in advanced triple-negative breast cancer (NCT02833766), the median progression-free survival was 3.5 months, with 73% of patients experiencing disease progression within the first year. Immunoliposomes hold promise as future therapeutic agents, especially when integrated with molecular diagnostics and patient-specific targeting strategies. However, their clinical translation requires overcoming biological and technological barriers to ensure reproducible efficacy and safety. This review critically examines current progress and explores future perspectives for this emerging therapeutic strategy in precision oncology.
Development of anti-EGFR targeted magnetic nanoparticles for doxorubicin delivery into triple negative breast cancer cells.
Lameli C, David S, Allard-Vannier E … +5 more , Dupeyrol G, Boursin F, Aubrey N, Chourpa I, Hervé-Aubert K
Eur J Pharm Biopharm · 2026 May · PMID 41651244 · Publisher ↗
A new generation of pH-responsive magnetic theranostic nanovectors (NV) has been developed to deliver doxorubicin (DOX) to triple negative breast cancer (TNBC) cells which overexpress epidermal growth factor receptor (EG...
A new generation of pH-responsive magnetic theranostic nanovectors (NV) has been developed to deliver doxorubicin (DOX) to triple negative breast cancer (TNBC) cells which overexpress epidermal growth factor receptor (EGFR). DOX was loaded onto functionalized NV using a pH-sensitive DOX-Fe complex (hereafter called NV-DOX). NV-DOX consist of superparamagnetic iron oxide nanoparticles (SPIONs), labelled with Dylight 680 fluorophore, and coated with a layer of covalently bound polyethylene-glycol (PEG) which is partially functionalized with anti-EGFR scFvs (average ratio is ≈12 scFvs per nanovector). The physico-chemical characteristics of the new nanovectors were suitable for IV injection: hydrodynamic diameter D below 150 nm, polydispersity index below 0.3 and slightly negative surface charge (≈ -10 mV). Thanks to the functional grafted scFvs, the NV-DOX were able to recognize the EGFR antigen efficiently. Using preformed DOX-Fe complex which binds to the SPION surface in a pH-dependent manner, about 6.5% w/w (DOX/iron oxide) of the drug was loaded onto the NV-DOX. The drug loading and release in its native form at acidic pH were characterized by surface-enhanced Raman scattering (SERS) spectroscopy. The dual fluorescent response of both Dylight680 and that of DOX was confirmed, which is promising for theranostic use of the nanovectors. Finally, the in vitro toxicity of NV-DOX on the EGFR-overexpressing TNBC cell line MDA-MB-468 was confirmed and compared to that of free DOX and NV without DOX. Together, all these properties of the NV-DOX are promising for their potential use as theranostic platform for TNBC treatment.
A way forward for generic development of telmisartan tablets: Integrating critical material attributes and bio-predictive dissolution for target product profile.
Pillai M, Shah RP, Sengupta P
Eur J Pharm Biopharm · 2026 May · PMID 41643868 · Publisher ↗
This study systematically integrated critical material attributes (CMAs) influencing drug release, focusing on factors such as particle size and excipient composition, and characterization of polymorphic form. As a model...
This study systematically integrated critical material attributes (CMAs) influencing drug release, focusing on factors such as particle size and excipient composition, and characterization of polymorphic form. As a model compound, a BCS class II drug Telmisartan was selected, and the methodology was evaluated using seven different formulations of Telmisartan through comprehensive analysis. The orthogonal analytical techniques, including chromatography, hot-stage microscopy, NMR spectroscopy, and dissolution testing were employed for evaluating critical quality attributes (CQAs). Systematic efforts were made to develop a biopredictive dissolution method using USP dissolution Apparatus I, II, and IV. Based on the t value of telmisartan, a multi-stage dissolution strategy was developed to understand the behaviour of formulation in acidic and neutral pH corresponding to the stomach and duodenum under fasting conditions. After de-formulation experiments, formulations were categorized into different buckets based on the size of API particles(d90 value of 8 ± 2 µm; 12 ± 2 µm and >15 µm), the type of excipients present (functional excipient and non-functional excipients), and the micro-environmental pH of the formulations. A rank-based approach was applied to evaluate a robust framework for understanding the differences between these generic formulations. This approach not only supports comprehensive formulation development through CMA-CQA correlations, but also aligns with regulatory expectations for adopting multi-dissolution methods as in vitro testing in cases of formulation change requirements with a bioequivalence waiver for post-approval formulation changes.
Two-birds-one-stone, microfluidic producing DES/W microemulsions to solubilize quercetin and penetrate intestinal mucosa for enhanced oral bioavailability.
Liu R, Yang X, Huang C … +4 more , Guan X, Li Y, Yang G, Yang Q
Eur J Pharm Biopharm · 2026 May · PMID 41633432 · Publisher ↗
Quercetin has antioxidant, anti-inflammatory, antibacterial, and anticancer effects. However, its therapeutic efficacy is limited by poor water solubility, low oral absorption, and limited bioavailability. In this study,...
Quercetin has antioxidant, anti-inflammatory, antibacterial, and anticancer effects. However, its therapeutic efficacy is limited by poor water solubility, low oral absorption, and limited bioavailability. In this study, a novel deep eutectic solvent (DES) in water (DES/W) microemulsion system was developed, wherein the DES was composed of DL-menthol and capric acid at a molar ratio of 7:3, to simultaneously accomplish enhanced quercetin solubilization and promoted mucosal permeation, both of which ensuring an adequate oral bioavailability and sufficient therapeutic effectiveness. Optimized DESs were used with microfluidic technology to create uniform quercetin-loaded DES/W microemulsions under the optimal formulation conditions: Tween 20 as the surfactant, a surfactant concentration of 1.37%, a continuous phase flow rate of 30.98 mL/h, and a dispersed phase flow rate of 3.15 mL/h. The results showed that the obtained microemulsions increased quercetin solubility, retention time in the intestines, and mucosal absorption, improving drug absorption and bioavailability. Pharmacokinetic studies showed that compared with free quercetin, the area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C) of the microemulsion formulation were significantly increased, with AUC being 5.54-fold higher than that of free quercetin. Notably, the use of microfluidic technology in preparing these microemulsions considerably reduces the need for surfactants, thus enhancing the biosafety of DES-based microemulsions. Overall, the DES/W microemulsions prepared by microfluidics could effectively addresses the challenges associated with poor absorption and low bioavailability of insoluble drugs with highly monodisperse and uniform formulations.
Strain- and species-specific immune responses to human adipose stem cell-derived extracellular vesicles: A comparative pharmacological evaluation in mice and human PBMCs.
Kim DO, Nguyen QT, Choi YC … +4 more , Choi JS, Lee KS, Cho YW, Yoo MH
Eur J Pharm Biopharm · 2026 May · PMID 41628693 · Publisher ↗
Human adipose stem cell-derived extracellular vesicles (hASC-EVs) have gained attention as potential cell-free therapeutics in regenerative medicine due to their immunomodulatory properties and low immunogenicity. Despit...
Human adipose stem cell-derived extracellular vesicles (hASC-EVs) have gained attention as potential cell-free therapeutics in regenerative medicine due to their immunomodulatory properties and low immunogenicity. Despite this promise, their immunotoxicity profile remains insufficiently characterized, particularly across species and genetic backgrounds. This study systematically assessed immune responses to repeated high-dose intravenous administration of hASC-EVs in two murine strains-C57BL/6 (inbred) and ICR (outbred)-and in human peripheral blood mononuclear cells (hPBMCs) in vitro. Flow cytometry of murine blood and spleen samples revealed transient, strain-dependent shifts in immune cell populations, including neutrophils, monocytes, macrophages, B cells, and NK cells. Notably, C57BL/6 mice exhibited more pronounced fluctuations than ICR mice, reflecting the role of host genetics in EV-induced immunomodulation. In contrast, hPBMCs exposed to equivalent concentrations of hASC-EVs displayed no significant changes in cell viability, immune cell subset composition, or activation markers over a 24-hour period. While a mild, transient increase in CD86 monocytes was observed at 6 h, this effect normalized by 12 h. These results suggest that hASC-EVs induce minimal and reversible immune responses in vivo and are immunologically inert in human immune cells under the tested conditions. The strain- and species-specific differences observed emphasize the limitations of rodent-only models for predicting human immunotoxicity and support the incorporation of human immune cell assays into preclinical safety assessments of EV-based therapeutics.
Preparation, Characterization, Pharmacokinetics, and Anti-Idiopathic pulmonary fibrosis activity of Bisdemethoxycurcumin liposomes.
Wang K, Wang Q, Adu-Frimpong M … +1 more , Ding H
Eur J Pharm Biopharm · 2026 Apr · PMID 41605301 · Publisher ↗
Bisdemethoxycurcumin (BDMC) exhibits anti-inflammatory, antioxidant, and antitumor properties. Nonetheless, there is currently no published evidence regarding its efficacy in the management of idiopathic pulmonary fibros...
Bisdemethoxycurcumin (BDMC) exhibits anti-inflammatory, antioxidant, and antitumor properties. Nonetheless, there is currently no published evidence regarding its efficacy in the management of idiopathic pulmonary fibrosis (IPF). Low solubility in water and reduced bioavailability of BDMC upon oral administration limit its application in the clinics. This study aimed to prepare D-α-tocopherol polyethylene glycol (PEG)-1000-succinate (TPGS)- and 1, 2-distearoyl-sn-glycero-3-phospho-ethanolamine (DSPE)-PEG-modified BDMC-loaded liposomes (BDMC-TPGS-DSPE-PEG-L) using the thin-film dispersion technique. Regarding formulation optimization, we employed single-factor experiments combined with Box-Behnken design (BBD). The physicochemical properties, in vitro release characteristics, and pharmacokinetic profiles of the prepared liposomes were systematically characterized. Furthermore, the anti-fibrotic activity of BDMC-TPGS-DSPE-PEG-L was evaluated in bleomycin (BLM)-induced A549 cells via MTT assay, senescence-associated β-galactosidase (SA-β-Gal) staining, and immunohistochemical analysis of Collagen-I. The optimal formulation showed favorable characteristics, namely particle size (PS), polydispersed index (PDI), zeta potential, encapsulation efficiency (EE%) and drug loading (DL) to be 232.36 ± 3.75 nm, 0.249 ± 0.016, -28.71 ± 0.976 mV, 95.98 ± 0.02%, and 6.84 ± 0.002%, respectively. The liposomal formulation significantly enhanced BDMC oral bioavailability by 1.6-fold compared to free BDMC. The results of the MTT assay confirmed that the cell inhibition rate of the liposome group decreased in a concentration-dependent manner, which was significantly lower compared to free drug group at the same concentration (P < 0.05). Moreover, microscopic observation showed that high-concentration liposome group significantly reduced senescence-associated β-galactosidase (SA-β-Gal) activity and type I collagen (Collagen-I) expression compared to free BDMC. Altogether, BDMC-liposomes could effectively improve the solubility and bioavailability of BDMC, thereby providing a novel therapeutic option for IPF.
Re-purposed phenobarbital-loaded squarticles: A novel approach for the topical management of chemotherapy-induced alopecia".
Fereig SA, Youshia J, El-Zaafarany GM … +2 more , Arafa MG, Abdel-Mottaleb MMA
Eur J Pharm Biopharm · 2026 Apr · PMID 41587585 · Publisher ↗
BACKGROUND: Chemotherapy-induced alopecia (CIA) causes significant psychological distress, prompting the need for effective prophylactic or therapeutic interventions. Phenobarbital, a potential agent for re-purposing tow...
BACKGROUND: Chemotherapy-induced alopecia (CIA) causes significant psychological distress, prompting the need for effective prophylactic or therapeutic interventions. Phenobarbital, a potential agent for re-purposing towards CIA prophylaxis and/or treatment, activates ABC receptors to expel chemotherapeutic agents from hair follicles. Squarticles, nanostructured lipid carriers enriched with squalene, are emerging nanocarriers that selectively target hair follicles via interaction with physiological sebum. METHODS: This study developed phenobarbital-loaded squarticles using a cost-effective high-speed stirring-ultrasonication method. Key formulation variables included total lipid amount (1% or 2%), precirol-to-squalene ratio (0:1, 3:1, 1:1, 1:0), and surfactant concentration (0.25% or 0.5%) RESULTS: The optimized formulation displayed a particle size of 229 ± 16.7 nm and drug entrapment efficiency of 82.72 ± 3.02%. Further characterization of the optimized formula demonstrated controlled drug release following the Higuchi pharmacokinetic model, with ∼ 11% of the drug deposited in hair follicles. Confocal laser scanning examination of skin specimens with DiI-loaded squarticles confirmed follicular targeting. In vivo studies on cyclophosphamide-induced alopecia in mice showed that both phenobarbital-loaded and blank squarticles provided a degree of hair follicle protection, accelerated recovery, and promoted cellular proliferation, as verified by histopathology, SEM imaging, and Ki-67 immunohistochemistry. CONCLUSIONS: Both blank and drug-loaded squarticles demonstrated potential as prophylactic/therapeutic agents against CIA.
Facile Formulation of an Oral Nanovesicular Carrier Co-Encapsulating Simvastatin and Ezetimibe for Enhanced Lipid-Lowering Effect.
Elfarouny AA, Haggag YA, Essa EA … +1 more , El-Gizawy SA
Eur J Pharm Biopharm · 2026 Apr · PMID 41565188 · Publisher ↗
Simvastatin/Ezetimibe (SIM/EZE) is a widely prescribed hypolipidemic drug combination that provides substantial cardiovascular protection, particularly in high-risk patients. However, its poor dissolution and extensive f...
Simvastatin/Ezetimibe (SIM/EZE) is a widely prescribed hypolipidemic drug combination that provides substantial cardiovascular protection, particularly in high-risk patients. However, its poor dissolution and extensive first-pass metabolism limit gastrointestinal bioavailability, necessitating higher doses and thereby increasing the risk of adverse effects. In this study, we report a facile, robust, and easily scalable cholesterol-surfactant based nanocarrier system to enhance the oral delivery of SIM/EZE. Nanoparticles were prepared using Span 60 or Tween 80 in combination with cholesterol and optimized via a 2 factorial experimental design. The effects of surfactant type, surfactant-to-cholesterol ratio, and sonication time on formulation characteristics were systematically investigated. The optimized formulation, prepared with 1200 mg Span 60, 300 mg cholesterol, 40 mg SIM, and 10 mg EZE and sonicated for 40 min, exhibited spherical morphology, a small particle size (109.6 nm), a zeta potential of (-37.91 mV), and high encapsulation efficiency (97.39 % for SIM and 88.79 % for EZE). Stability testing confirmed the absence of degradation under physiological conditions and showed no significant changes over three months of storage. In vivo evaluation in a hyperlipidemic rat model demonstrated that the optimized formulation significantly reduced total cholesterol levels compared with both the marketed product (Inegy™) and the drug suspension, indicating enhanced oral absorption. These findings highlight the potential of this nanoparticle system as an effective platform to improve the therapeutic efficacy of the SIM/EZE fixed-dose combination.
A refined coadministration regime to mitigate immunological clearance of biomedical nanoparticles.
Schorr K, Konrad J, Birringer J … +3 more , Damm C, Breunig M, Goepferich A
Eur J Pharm Biopharm · 2026 Apr · PMID 41558551 · Publisher ↗
Nanoparticles are frequently designed as carriers to mediate the active transport of their cargo to the site of action, thereby serving as effector particles. However, after their in vivo administration, they become quic...
Nanoparticles are frequently designed as carriers to mediate the active transport of their cargo to the site of action, thereby serving as effector particles. However, after their in vivo administration, they become quickly recognized by immune cells and are cleared from the systemic circulation. This significantly impairs the nanoparticles' targeting efficiency and shifts the target/off-target ratio toward metabolizing organs. As engineering-driven strategies, such as the PEGylation of their surface, require major modifications of the nanoparticles' structure and do not appear to achieve the desired level of effectiveness, synergistic approaches are attracting increasing attention. They rely on the transient blockade of the immune system through endocytosis inhibitors or decoy nanomaterials. In the present study, we introduce a further development of these synergistic approaches by loading lipid nanocapsules (LNCs) as decoy nanoparticles with the endocytosis inhibitor chloroquine. Two principal advantages can be ascribed to this refined synergistic approach: First, encapsulation of the endocytosis inhibitor paves the way for pioneering subcutaneous application as a novel route of administration for the effector nanoparticles, as phagocytic cells within the lymphatic system can be selectively targeted. Second, the established co-administration regime constitutes a transferable concept across diverse settings without the need for structural modifications of the respective effector nanoparticles. Here, we report the successful in vitro establishment of this refined coadministration regime. Preincubation with chloroquine-loaded LNCs led to a statistically significant uptake inhibition of model effector nanoparticles into macrophages. Moreover, we investigated, for the first time, the incorporation of 1,2-Dioleoyl-sn-glycero-3-phosphoserine as a macrophage-specific targeting structure into the decoy LNCs' envelope and its effect on the phagocytosis activity of macrophages.
The THP-1 cell line as a model for the assessment of monoclonal antibodies aggregates' immunological effects.
Lteif M, Abratanska S, Turbica I … +1 more , Pallardy M
Eur J Pharm Biopharm · 2026 Apr · PMID 41554462 · Publisher ↗
Immunogenicity is a major challenge to the development of biotherapeutics, and it is now well admitted that aggregation of therapeutic antibodies contributes to inducing an immunogenic response. The aim of this work was...
Immunogenicity is a major challenge to the development of biotherapeutics, and it is now well admitted that aggregation of therapeutic antibodies contributes to inducing an immunogenic response. The aim of this work was to investigate the THP-1 cell line as a model to evaluate antibodies (Ab) aggregates' immunological effects, by studying internalization and cell activation. We generated aggregates by submitting infliximab (IFX), an immunogenic anti-TNF-α chimeric Ab, to a heat stress for various time of incubation. Of importance, some IFX aggregates, that were generated in mild conditions, altered THP-1 phenotype. Our results also showed that IFX aggregates are more internalized by THP-1 compared to the native antibody. Larger IFX aggregates, in particular, were able to modify THP-1 cells phenotype through the activation of the FcγRIIa-Syk pathway and to activate Syk in a Src-dependent manner. ERK kinase was also activated. Taken together, our results highlight the possibility of using the THP-1 cell line to assess the biological effects of Abs aggregates by measuring membrane markers and internalization.
Fabrication of bioprints self-coated with thermally sensitive lactobacilli for CAUTI applications.
Maners C, Kyser AJ, Verhoeven D … +4 more , Fotouh B, Greiner A, Gilbert NM, Frieboes HB
Eur J Pharm Biopharm · 2026 Apr · PMID 41544720 · Full text
Catheter-associated urinary tract infections (CAUTI) represent a large healthcare burden, accounting for a substantial portion of hospital-acquired infections in the United States. Solutions such as intermittent catheter...
Catheter-associated urinary tract infections (CAUTI) represent a large healthcare burden, accounting for a substantial portion of hospital-acquired infections in the United States. Solutions such as intermittent catheterization and catheter surface coatings with antibiotics or silver nanoparticles have offered limited success in preventing uropathogen biofilm formation on the catheter or in promoting a healthy urinary tract. This study explores a novel self-coating biomaterial approach for CAUTI applications, with the goal to promote antibacterial interference. A new fabrication technique is developed to incorporate thermally sensitive Lactobacillus bacteria into a silicone-based polymer. These species are known for their probiotic capabilities and were selected as a means for the material to self-coat with them. Using 3D-printed CAD-designed molds and bio-injection molding, "living probiotic carrier" catheter segments were formed with the probiotic-containing bioink. Lactobacillus-containing segments immersed in artificial urine media (AUM) increased in mass up to 7 days and remained stable at physiological conditions. Increased absorbance via crystal-violet staining indicated biomass accumulation while SEM imaging revealed a visibly large probiotic presence on the segment intraluminal surface over 7-day submersion in AUM. Mechanical integrity testing yielded Shore A hardness values within clinically acceptable ranges. TGA and DSC thermal stability analyses suggested that probiotic presence could affect silicone crosslinking, highlighting the need to fine-tune loading amount and composition of bacterial species to achieve desired polymeric degradation. Overall, the results demonstrate promising biomaterial properties along with lactobacilli biofilm formation, highlighting the potential for silicone catheters self-coated by thermally sensitive lactobacilli to offer a bacterial interference strategy against CAUTI.
Computational analysis of the impact of urine volume on magnetic nanoparticle hyperthermia in the treatment of non-muscle-invasive bladder cancer.
Marami S, Tavakoli MH, Pashaki AS … +1 more , Nikzad S
Eur J Pharm Biopharm · 2026 Apr · PMID 41544719 · Publisher ↗
Magnetic nanoparticle hyperthermia (MNP-HT) has emerged as a promising non-invasive technique for targeted cancer therapy. This study presents a comprehensive computational analysis of the influence of urine volume on th...
Magnetic nanoparticle hyperthermia (MNP-HT) has emerged as a promising non-invasive technique for targeted cancer therapy. This study presents a comprehensive computational analysis of the influence of urine volume on the efficacy of MNP-HT for the treatment of T1 non-muscle-invasive bladder cancer (NMIBC). A two-dimensional axisymmetric finite element model was developed, coupling solid tissue heat transfer with intravesical fluid dynamics. Magnetite (FeO) nanoparticles with a mean diameter of 19 nm were excited using an alternating magnetic field at a frequency of 100 kHz. Four clinically relevant urine volumes (60, 120, 240, and 400 mL) were simulated to evaluate their effects on magnetic field distribution, nanoparticle power dissipation, convective heat transfer, and temperature distributions in both tumor and surrounding healthy tissues. Tissue heating was modeled using the Pennes bioheat equation, while urine flow and thermal transport were governed by the Navier-Stokes and energy equations. The results demonstrate a clear inverse relationship between urine volume and hyperthermia efficiency. Average tumor temperatures decreased from 41.89 °C at 60 mL to 41.51 °C at 400 mL due to enhanced convective cooling and reduced magnetic field-dependent nanoparticle power dissipation, while healthy tissue temperatures remained within safe therapeutic limits. These findings highlight urine volume as a critical physiological parameter influencing MNP-HT performance. To optimize thermal efficacy, clinical protocols should aim to minimize bladder urine volume before and during treatment through bladder emptying strategies and careful monitoring of bladder refilling.
Trp2 cationic liposomes doped with manganese adjuvant potently activate dendritic cells to enhance antitumor activity against melanoma in mice.
Ding C, Li H, Han P … +1 more , Zhao Y
Eur J Pharm Biopharm · 2026 Apr · PMID 41539498 · Publisher ↗
Tyrosinase-related protein 2 (Trp2) peptide-based vaccines hold great promise for melanoma immunotherapy, however, their application is often limited by inefficient antigen delivery, inadequate dendritic cell (DC)-mediat...
Tyrosinase-related protein 2 (Trp2) peptide-based vaccines hold great promise for melanoma immunotherapy, however, their application is often limited by inefficient antigen delivery, inadequate dendritic cell (DC)-mediated immune activation, and an immunosuppressive tumor microenvironment. To address these challenges, we developed an engineered cationic liposome vaccine platform for co-delivering Trp2 and a manganese-based adjuvant (MnJ). The Trp2-DOTAP-Lipo/MnJ system facilitates efficient antigen delivery to antigen-presenting cells via electrostatic interactions between the cationic lipid bilayer and negatively charged cell membranes, significantly enhancing antigen uptake, promoting DC maturation, stimulating the secretion of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) and levels of interleukin-6 (IL-6), and increasing cytotoxic T lymphocyte infiltration. Acting as a key amplifier of antigen-specific immunity, MnJ enhances antigen presentation and effector functions, which together with its role in localizing cytokine production, potently enhances anti-tumor immunity while minimizing systemic toxicity. In a murine melanoma model, Trp2-DOTAP-Lipo/MnJ exhibited significantly improved tumor suppression and extended survival. By combining nanocarrier engineering with innate immune activation, this strategy offers a robust combinatory therapeutic approach for melanoma, leveraging efficient antigen delivery and localized immunomodulation to overcome key obstacles in cancer immunotherapy.
Injectable poloxamer-based thermogel as a delivery platform for agmatine and hyaluronic acid in muscle tissue engineering.
Qutub M, Tatode A, Premchandani T … +2 more , Taksande J, Umekar M
Eur J Pharm Biopharm · 2026 Mar · PMID 41519311 · Publisher ↗
Volumetric muscle loss (VML) results in permanent functional deficits for which current therapeutic strategies are insufficient. We hypothesized that an injectable, thermoresponsive hydrogel enabling localized delivery o...
Volumetric muscle loss (VML) results in permanent functional deficits for which current therapeutic strategies are insufficient. We hypothesized that an injectable, thermoresponsive hydrogel enabling localized delivery of agmatine sulfate (AgS) and hyaluronic acid (HA) could synergistically promote robust neuromuscular regeneration. A poloxamer-based thermogel was systematically optimized using a 3 full factorial design. The lead formulation exhibited a physiologically advantageous gelation temperature (27 ± 1.03°C) and time (42 ± 1.4 s), with rapid bioactive release (85-90% within 18-24 h) matched to the critical satellite cell activation window. In vitro degradation studies confirmed complete gel erosion, providing burst delivery during the acute injury phase. In a rat tibialis anterior VML model, the AgS-HA combination therapy demonstrated profound synergistic effects, restoring grip strength and normalizing complex gait parameters to near-control levels. This functional recovery was corroborated by significantly reduced serum creatine kinase, indicating reduced muscle damage. Histopathological analysis revealed near-complete restitution of mature, organized myofiber architecture with minimal fibrosis, contrasting with extensive scar tissue in control groups. Notably, functional recovery occurred without significant modulation of systemic inflammatory markers (IL-6, IL-10, TNF-α), suggesting regeneration proceeds through direct pro-myogenic, anti-fibrotic, and neurovascular mechanisms rather than systemic anti-inflammatory effects. These findings demonstrate that a thermoresponsive hydrogel platform for rapid AgS and HA delivery effectively promotes comprehensive structural and functional recovery, representing a potent and clinically translatable strategy for VML.
Cationic liposome-mediated intra-articular delivery of lorecivivint for osteoarthritis treatment.
Gonzalez-Fernandez P, Morici L, Simula L … +4 more , Takwa R, Benabdellah A, Allémann E, Jordan O
Eur J Pharm Biopharm · 2026 Mar · PMID 41519310 · Publisher ↗
Osteoarthritis (OA) is the most common joint disease worldwide causing cartilage loss, inflammation and pain. Lorecivivint (LOR) is a new disease-modifying osteoarthritis drug (DMOAD) that targets the Wnt pathway to impr...
Osteoarthritis (OA) is the most common joint disease worldwide causing cartilage loss, inflammation and pain. Lorecivivint (LOR) is a new disease-modifying osteoarthritis drug (DMOAD) that targets the Wnt pathway to improve cartilage regeneration and reduce the pro-inflammatory cytokines production. However, its advancement in the clinical evaluation is facing certain challenges due to poor solubility and fast clearance from the joint. Our study is the first to improve LOR delivery using cationic liposomes for intra-articular injection. DSPC-Chol-DOTAP-based liposomes were formulated using microfluidics with an encapsulation efficiency (EE) of 36 % of LOR and increasing the drug solubility over 120-fold in PBS and 100-fold in simulated synovial fluid. In a physiological environment, a prolonged release of 17 % of the LOR over 14 days was achieved, while faster release of 65 to 86 %, respectively, was observed in simulated synovial fluid. The surface charge of + 35 mV and the size of 145 nm were influential in increasing cartilage uptake in bovine explant of 1.4-fold and 3.6-fold compared to free LOR solution and suspension, respectively. In vitro study by flow cytometry revealed there was no cytotoxicity at 10 nM in human chondrocytes (hCHs) and in human mesenchymal stem cells (MSCs). Nevertheless, some toxicity-related morphological changes in hCHs spheroids were observed at 300 nM, which corresponds to the IC80 of LOR. The safer liposomal concentration of 10 nM maintained the drug bioactivity and reduced by half TGF-β and IL-6 levels in two-dimensional hCHs and MSCs cell culture, which confirmed the anti-fibrotic and anti-inflammatory effects. An in vivo pilot study was conducted using a severe ACLT-hMnX rat model showing preliminary evidence of an alleviated osteophyte formation and reduced cartilage matrix loss in the medial tibial plateau. Overall, Lipo-LOR improved drug solubility, release and cartilage retention, which are critical requirements for implementing a localized intra-articular OA therapy.
A new drug-drug co-amorphous system of imipramine and celecoxib with improved solubility and synergistic antinociceptive effects.
Chen Z, Zhou H, Song J … +5 more , Xu B, Wang C, He F, Zhang G, Zhuang T
Eur J Pharm Biopharm · 2026 Mar · PMID 41519309 · Publisher ↗
Because the monotherapy of currently available pain killers often shows serious adverse effects or limited efficacy for treating neuropathic pain, multimodal analgesia has been highly recommended to gain improved antinoc...
Because the monotherapy of currently available pain killers often shows serious adverse effects or limited efficacy for treating neuropathic pain, multimodal analgesia has been highly recommended to gain improved antinociceptive effects and reduce dose-dependent side effects. Drug-drug co-amorphous systems emerge as a useful strategy for ameliorating the physicochemical properties of drug substances and achieving clinical benefits compared with individual components. New drug-drug co-amorphous products IMI-CEL at different ratios were prepared from imipramine hydrochloride (IMI) and a poorly water-soluble anti-inflammatory drug-celecoxib (CEL) by melt-quenching method, which were characterized by XRPD, DSC and IR. Co-amorphous product IMI-CEL (1:1) displayed notable improvement in the solubility (64.4 times) and dissolution rate (3.1 times) than crystalline CEL in pH 6.8 buffer, and IMI-CEL exhibited good physical stability under long-term storage conditions. Isobolographic analysis demonstrated that IMI-CEL (1:1) showed synergistic analgesic effects in paclitaxel-induced neuropathic pain in mice. Moreover, the oral bioavailability of 1:1 IMI-CEL was improved 1.396 times in rats when compared to the single drug. Above results suggested the potential of IMI-CEL to produce synergistic analgesic effects through developing drug-drug co-amorphous systems.
Rifampicin-containing interpenetrating hydrogel networks (IHNs) based on poly(methacrylates) and Poloxamers, and their potential as short-duration use antimicrobial medical device biomaterials.
Jones DS, Westwood M, Li S … +1 more , Andrews GP
Eur J Pharm Biopharm · 2026 Apr · PMID 41519308 · Publisher ↗
This study describes the surface, mechanical, swelling, microbial anti-adherence and drug release properties of rifampicin-containing interpenetrating hydrogel networks (IHNs) composed of either poly(hydroxyethylmethacry...
This study describes the surface, mechanical, swelling, microbial anti-adherence and drug release properties of rifampicin-containing interpenetrating hydrogel networks (IHNs) composed of either poly(hydroxyethylmethacrylate, p(HEMA)) or poly(methacrylic acid, p(MAA)) and Poloxamer block copolymers (grades F127, P123 and L121), prepared using free radical polymerisation and designed as coatings for urinary medical devices. The swelling and mechanical properties of the IHNs were affected by the polymethacrylate type, Poloxamer grade and concentration. Incorporation of Poloxamers decreased the crosslink density and increased the pore size of the hydrogels at pH 7.2 (calculated from swelling data), leading to enhanced IHN swelling and reduced ultimate tensile strength and Young's Modulus. The static contact angles of the IHNs depended on the type of polymethacrylate but not on the Poloxamer grade/concentration. In particular, the contact angles of p(HEMA) IHNs were greater than for p(MAA) IHNs. The contact angles of p(MAA) IHNs at pH 4 were greater than those at pH 7.2. ATR-FTIR confirmed the presence of PEO at the surface of p(MAA)/F127 IHNs. Drug loading into (by swelling) and subsequent release at pH 7.2 buffer depended on polymethacrylate type, grade and concentration of Poloxamers. Rifampicin release from p(MAA) IHNs was significantly greater than from comparator p(HEMA) IHNs, due to both the greater loading of rifampicin and the increased pore size of these hydrogels. The mass of rifampicin loaded into the hydrogels was greater for p(MAA) IHNs Release of rifampicin from p(MAA) hydrogels at pH 4 (pre-swollen in rifampicin solutions at pH 7.2) involved burst release (dependent on and reduced by increasing concentration of Poloxamer), followed by slow, controlled release, again affected by Poloxamer concentration. p(HEMA) p(HEMA) IHNs significantly decreased microbial adherence, with the inclusion of rifampicin inhibiting microbial adherence at 4 h (for selected IHNs) and 24 h. Microbial adherence to rifampicin-containing p(MAA) IHNs following a 4-hour contact time was inhibited; however, given the rapid drug release, prolonged anti-adherence is unlikely. Conversely, the ability of Poloxamers to enhance and offer both greater control of rifampicin release from p(HEMA) IHNs and the more prolonged anti-adherence effects make these platforms more suitable for urinary application.
Enhancing bioavailability of a weakly basic drug through cocrystallization: PBPK modeling of ketoconazole-succinic acid.
Santos Goes AK, Soliman A, Kowthavarapu VK … +2 more , Oliveira PR, de Moraes NV
Eur J Pharm Biopharm · 2026 Mar · PMID 41513155 · Publisher ↗
Pharmaceutical cocrystals, formed by combining an active pharmaceutical ingredient (API) with a suitable coformer, offer a promising strategy to enhance drug solubility, stability, and dissolution, thereby improving abso...
Pharmaceutical cocrystals, formed by combining an active pharmaceutical ingredient (API) with a suitable coformer, offer a promising strategy to enhance drug solubility, stability, and dissolution, thereby improving absorption and bioavailability without altering pharmacological properties. This approach is particularly advantageous for poorly soluble drugs such as ketoconazole (KTZ), a BCS Class II compound characterized by dissolution-limited absorption and variable oral bioavailability. As a weak dibasic drug, KTZ exhibits pH-dependent dissolution, which was favored under acidic gastric conditions. To overcome the pH-dependent dissolution, a cocrystal of KTZ with succinic acid (SA) was developed and a physiologically based pharmacokinetic (PBPK) approach informed by in vitro solubility and dissolution data was used to predict KTZ plasma concentration profiles, following administration of KTZ or KTZ-SA cocrystal. The developed PBPK model was verified, with a predicted/observed AUC ratio within a 2-fold range for KTZ. The model successfully captured the reduced exposure to KTZ when administered with omeprazole. PBPK simulations demonstrated a reduced KTZ exposure following a 200 mg dose under achlorhydric conditions (AUC: 1.1 µg·h·mL-1) or with omeprazole administration (AUC: 3.1 µg·h·mL-1), compared to healthy subjects (AUC: 12.2 µg·h·mL-1). In contrast, KTZ-SA cocrystal achieved consistently similar exposure in healthy subjects (AUC: 17.2 µg·h·mL-1), achlorhydric populations (AUC: 18.6 µg·h·mL-1), or when coadministered with omeprazole (AUC: 16.9 µg·h·mL-1). This model-based approach has demonstrated the potential of KTZ-SA cocrystal to enhance bioavailability in populations with achlorhydria-related disparities, effectively addressing the challenges posed by variable gastric acidity. The findings support the development of pharmaceutical cocrystals to optimize drug delivery and maximize therapeutic outcomes.
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