European Journal Of Pharmaceutics And Biopharmaceutics[JOURNAL]
Sun
200 papers
Ciliation and mucus secretion in an in vitro model of nasal mucosa based on CI-pNaEC cell line for preclinical drug testing.
Klintz LPI, Reichl S
Eur J Pharm Biopharm · 2026 Jul · PMID 42401318 · Publisher ↗
In preclinical development of nasal drug formulations, in vitro models of the nasal mucosa offer a viable alternative to animal testing. The novel cell line CI-pNaEC produces mucus and develops motile ciliation, thereby...
In preclinical development of nasal drug formulations, in vitro models of the nasal mucosa offer a viable alternative to animal testing. The novel cell line CI-pNaEC produces mucus and develops motile ciliation, thereby adequately emulating key characteristics of human nasal epithelium. In this study, ciliation and mucin secretion in CI-pNaEC was further investigated. Mucin expression was quantified and fluorescence recovery after photobleaching (FRAP) assays were used to evaluate the mucus diffusion barrier. In addition, the contribution of the mucus barrier to drug permeation was evaluated. The thickness of the CI-pNaEC-derived mucus and the diffusion barrier were within the ranges reported for healthy mucus. Cilia length in CI-pNaEC cultures corresponded to physiological conditions, although overall ciliation density remained lower than in vivo. However, coordinated mucus transport can be observed in some areas of the CI-pNaEC cultures, which could lead to mucociliary clearance with further optimization. These results highlight CI-pNaEC as a promising in vitro model for mimicking human nasal mucosa in the preclinical assessment of intranasal drug delivery systems.
Long-term physical stability of lyophilized carbohydrate matrices assessed by positron annihilation lifetime spectroscopy.
Shiga Y, Sakurai N, Chiari L
Eur J Pharm Biopharm · 2026 Jul · PMID 42401317 · Publisher ↗
Understanding long-term physical changes in lyophilized matrices is essential for rational formulation design and stability assessment. In this study, positron annihilation lifetime spectroscopy (PALS) was applied to mon...
Understanding long-term physical changes in lyophilized matrices is essential for rational formulation design and stability assessment. In this study, positron annihilation lifetime spectroscopy (PALS) was applied to monitor time-dependent structural evolution in simple lyophilized carbohydrate-polymer matrices stored for up to 21 months under low and elevated humidity conditions. Formulations containing saccharides, polyols and starch were selected as model amorphous systems to investigate molecular mobility and phase evolution in the absence of active pharmaceutical ingredients. The free volume and ortho-positronium (o-Ps) intensity were determined as complementary indicators of free volume within the amorphous phase and relative amorphous fraction, respectively. Over prolonged storage, composition- and humidity-dependent changes in these parameters were observed. Under elevated humidity, selected formulations exhibited reductions in o-Ps intensity consistent with partial recrystallization, while variations in free volume reflected concurrent structural relaxation within the remaining amorphous phase. Solid-state H NMR and X-ray diffraction provided complementary support for these evolution trends. The results demonstrate that PALS sensitively detects physical aging and structural changes in lyophilized matrices by probing free-volume evolution during storage. These findings support the utility of PALS as a non-destructive analytical tool for monitoring long-term physical stability of amorphous lyophilized matrices under defined environmental conditions.
Partition-controlled drug release from polymeric nanocapsules: A physically consistent framework with formulation-specific corrections.
de Albuquerque MAS, de Albuquerque DF
Eur J Pharm Biopharm · 2026 Jul · PMID 42392377 · Publisher ↗
Mathematical models for drug release from polymeric nanocapsules have traditionally relied on Noyes-Whitney-based first-order kinetics, which implicitly predict faster release for drugs exhibiting higher solubility in th...
Mathematical models for drug release from polymeric nanocapsules have traditionally relied on Noyes-Whitney-based first-order kinetics, which implicitly predict faster release for drugs exhibiting higher solubility in the oily core. This prediction is inconsistent with numerous experimental observations in which more lipophilic compounds are released more slowly. To address this apparent paradox, a partition-controlled kinetic framework is derived in which the effective release rate scales inversely with oily-core solubility. The resulting model, [Formula: see text] introduces a dimensionless correction factor α and a reference solubility S, yielding a dimensionally consistent formulation while preserving the mechanistic inverse-solubility dependence predicted by partition equilibrium arguments. A re-analysis of the previously published nanocapsule model reveals a dimensional inconsistency and a tabulation error affecting the reported kinetic parameters. After correction, the published adapalene data are found to be consistent with the proposed inverse-solubility scaling. The model is further evaluated using four release datasets (adapalene in two oily cores, capsaicin, and dihydrocapsaicin), yielding R values between 0.925 and 0.969 with C fixed at the final experimental value. These results support partition-controlled release as a physically plausible and dimensionally consistent framework for describing drug release from polymeric nanocapsules.
Formulation-dependent differences in systemic glutathione availability: Comparative pharmacokinetics of orally dissolving film and tablet formulations in healthy adults.
Jung ES, Jang HY, Jung SJ … +5 more , Kim BH, Kim YJ, Moon JH, Chae SW, Lee SO
Eur J Pharm Biopharm · 2026 Jul · PMID 42392376 · Publisher ↗
BACKGROUND: Glutathione is a tripeptide involved in antioxidant defense; however, its systemic availability following oral administration remains controversial, and pharmacokinetic differences between formulations in hum...
BACKGROUND: Glutathione is a tripeptide involved in antioxidant defense; however, its systemic availability following oral administration remains controversial, and pharmacokinetic differences between formulations in humans are not well characterized. OBJECTIVE: This study compared the pharmacokinetics and short-term supplementation effects of an orally dissolving film (ODF) and a conventional tablet formulation of glutathione in healthy adults. METHODS: In Study I, a randomized open-label crossover trial evaluated single-dose (300 mg) pharmacokinetics following administration of ODF or tablets. In Study II, participants consumed ODF (100 mg/day) or tablets (100 mg/day) for 4 weeks. RESULTS: Plasma glutathione concentrations were higher in the ODF group, with significant differences at 4 and 6 h. The ODF formulation showed a longer T and tended toward higher C and systemic exposure (iAUC). During 4-week supplementation, both formulations increased circulating glutathione levels, with no significant changes in oxidative stress-related biomarkers. No adverse events were reported. CONCLUSIONS: The ODF formulation exhibited a distinct pharmacokinetic profile and showed a trend toward greater systemic glutathione exposure compared with the tablet formulation. These findings suggest that formulation characteristics may contribute to differences in the bioavailability and pharmacokinetic behavior of orally administered glutathione. CLINICAL TRIAL REGISTRATION: Clinical Research Information Service (CRIS), KCT0011710.
Does magnesium permeate the skin? An ex vivo investigation of magnesium ion delivery through intact and barrier-disrupted skin.
Camili V, Stürup S, Heinz A
Eur J Pharm Biopharm · 2026 Jun · PMID 42372834 · Publisher ↗
The potential for cutaneous magnesium delivery remains uncertain despite widespread use of topical formulations. This study aimed to directly evaluate magnesium ion permeation from a saturated aqueous magnesium sulfate m...
The potential for cutaneous magnesium delivery remains uncertain despite widespread use of topical formulations. This study aimed to directly evaluate magnesium ion permeation from a saturated aqueous magnesium sulfate monohydrate solution across porcine skin using an ex vivo Franz diffusion cell model. Permeated magnesium was quantified by inductively coupled plasma mass spectrometry in both intact and tape-stripped porcine skin, the latter representing impaired barrier conditions. Minimal magnesium permeation was observed across intact skin, with no significant difference between magnesium-treated and control samples, where magnesium permeation after 24 h was found to be 8.3 ± 3.4 µg cm (magnesium-treated) as compared to 3.9 ± 0.8 µg cm (control). In contrast, tape stripping resulted in a marked increase in magnesium permeation to approximately 13.0 ± 5.3 mg cm, representing an increase of several orders of magnitude. Substantial inter-individual variability was observed in barrier-impaired skin. The findings of this study demonstrate that magnesium permeation is strongly limited by the stratum corneum and that transdermal delivery from simple aqueous solutions is unlikely under normal physiological conditions. However, significantly enhanced permeation may occur in compromised skin. Overall, the study highlights the critical role of skin barrier integrity in regulating magnesium permeation and provides insight into the limitations of topical magnesium application.
Surface engineering of graphene as a novel nano-carrier for doxorubicin using sugar-based deep eutectic systems.
Zainal-Abidin MH, Hayyan M, Ngoh GC … +5 more , Wong WF, Looi CY, Abdul Rahman MB, Salim N, Fei TE
Eur J Pharm Biopharm · 2026 Jun · PMID 42372833 · Publisher ↗
The future of graphene as a drug nano-carrier lies in nanotechnolgy where it can be tailor-made to favor the cellular biological environment. Therefore, an innovative route was implemented to improve the biocompatibility...
The future of graphene as a drug nano-carrier lies in nanotechnolgy where it can be tailor-made to favor the cellular biological environment. Therefore, an innovative route was implemented to improve the biocompatibility of graphene using binary and ternary sugar-based deep eutectic systems (DESs) as green functionalizing agents with composition of choline chloride (ChCl):glucose (2:1), ChCl:fructose (2:1), ChCl:fructose:water (5:2:5), and ChCl:glucose:water (5:2:5). The changes in physicochemical properties of sugar-based DES-functionalized graphene were observed via FESEM, FTIR, BET, XRD, and Raman spectroscopy, testifying the addition of DES-functional groups. The biocompatibility of graphene was significantly improved post functionalization with sugar-based ternary DES compared to sugar-based binary DES as validated in biological assays. The ternary DES-functionalized graphene demonstrated higher doxorubicin (DOX) loading capacity as compared to the binary DES-functionalized graphene. To gain molecular-level insights, computational simulations via quantum chemical calculations were performed to elucidate the interactions between graphene, DES components, and DOX. After DOX loading, the graphene exhibited damaging impacts against cancerous cells through the intracellular ROS production and cell cycle disruption phenomena. Real-time cell growth analysis was further investigated to confirm the cytotoxicity kinetic response of DOX loaded-Gr against cancerous cells over time. The results of this cellular kinetic response were in accordance with the DOX loading capacity data. Sugar-based ternary DESs ChCl:glucose:water and ChCl:fructose:water, were the most promising functionalizing agents for nano-drug carrier, owing to their lower cytotoxicity, higher drug loading capacity and a significant inhibition on the cancer cell growth profile.
Buprenorphine long acting injectables: clinical needs, pharmacodynamic and pharmacokinetic basis, and design challenges for solid preformed implants.
Wang T, Biswas AA, Zhang F … +2 more , Sun R, Hu M
Eur J Pharm Biopharm · 2026 Jun · PMID 42364665 · Publisher ↗
With annual overdose deaths in the United States over 1 million, medication-assisted treatment (MAT) with buprenorphine (BUP) remains the first-line, gold-standard therapy for opioid use disorder (OUD). Because OUD is a...
With annual overdose deaths in the United States over 1 million, medication-assisted treatment (MAT) with buprenorphine (BUP) remains the first-line, gold-standard therapy for opioid use disorder (OUD). Because OUD is a chronic, relapsing condition that requires long-term pharmacotherapy, long acting injectables (LAI) and implantable formulations offer important advantages over daily formulations for maintenance treatment. By comparing transmucosal BUP and LAI formulations' systemic exposure profiles and μ-opioid receptor (MOR) occupancy, converging data demonstrate that higher and more sustained BUP exposure with low variability is required to fully suppress withdrawal, cravings, and illicit opioid use. These findings indicated that currently marketed formulations may not adequately address the clinical challenges associated in the fentanyl/polysubstance era. Accordingly, this rationale-based review proposes a mechanistic framework supporting the development of next-generation BUP-PLGA solid biodegradable implants to maintain a conservative therapeutic benchmark (e.g. Css ≥ 5 ng/mL) for extended durations (e.g. 3-6 months) with low variability (e.g. no large burst release, major lag phase or phase inversion). However, progress in implant development has been hindered by limited mechanistic understanding of drug release. In PLGA-BUP systems, poor IVIVC is largely driven by the low and pH-dependent solubility of BUP, which can make dissolution rate-limiting in vivo and interact with the evolving PLGA acidic microenvironment (acidification, porosity formation, and autocatalytic degradation). Future research should be prioritized to determine directly whether polymer erosion coincides with drug release in PLGA depots, or whether residual, poorly soluble BUP persists locally and releases under dissolution-limited kinetics. Clarifying these mechanisms is not only essential to fulfill the regulatory and translational expectations of the FDA and NIDA, but also to deepen mechanistic understanding and accelerate the rational development of LAI formulations for poorly soluble drug.
Design rules for externally triggered drug uncaging under optical and radiolytic regimes.
Hanif H, Neupane P, Garrett LF … +2 more , David SR, Suyama TL
Eur J Pharm Biopharm · 2026 Jun · PMID 42364664 · Publisher ↗
Externally triggered prodrug activation can improve therapeutic index by decoupling systemic distribution from pharmacological activity. This review examines prodrug uncaging strategies enabled by electromagnetic radiati...
Externally triggered prodrug activation can improve therapeutic index by decoupling systemic distribution from pharmacological activity. This review examines prodrug uncaging strategies enabled by electromagnetic radiation through the lens of activation physics and clinical constraints, spanning UV-visible-near-infrared photochemistry and ionizing radiation. Differences in clinical applicability arise from fundamentally contrasting activation physics and irradiation geometry. While recent reviews have cataloged externally triggered prodrug systems across multiple modalities, we instead organize the field by activation regime and evaluate these systems under clinically realistic constraints. In photochemical activation, direct light-chromophore coupling enables predictable bond cleavage through defined excited-state pathways, but effective application is constrained by tissue optics and beam-sample geometry. X- and γ-rays penetrate deeply into tissues, but their uncaging pathway is indirect via diffusible water radiolysis products, resulting in stochastic rather than deterministic cleavage chemistry. We evaluate these platforms using deliverability, irradiation geometry, dose efficiency under clinically realistic conditions, microenvironment dependence, and functional group compatibility. We conclude with practical design rules and a decision framework that aligns targeted pathology and treatment objectives with the appropriate trigger chemistry, payload selection, and delivery strategy under the governing activation physics.
Systematic evaluation of cryopreservation parameters for natural killer cells in clinically relevant cyclic olefin polymer vials.
Juliano M, Garcia B, Nguyen H … +3 more , Potnis M, Cornell L, Khan K
Eur J Pharm Biopharm · 2026 Jun · PMID 42364663 · Publisher ↗
BACKGROUND AIMS: Allogeneic cell therapy uses donor-derived cells to treat disease indications in oncology, autoimmune disorders, and other areas. Unlike patient-specific autologous therapies, allogeneic therapies are ma...
BACKGROUND AIMS: Allogeneic cell therapy uses donor-derived cells to treat disease indications in oncology, autoimmune disorders, and other areas. Unlike patient-specific autologous therapies, allogeneic therapies are manufactured in large batches. For these products, the final containment is critical for maintaining cell viability and function. Factors such as material composition, container closure integrity at cryogenic temperatures, and container-cell interactions directly affect post-thaw recovery and performance. This study evaluates key cryogenic storage parameters for NK-92 cells used in allogeneic therapies in a clinically relevant cyclic olefin polymer (COP) vial. METHODS: In this study, parameters such as freezing rate, cell density, and the presence of DMSO as a cryoprotective agent during the freezing process in COP vials were evaluated. Additionally, the effect of ice nucleation was measured, and a direct comparison of freezing these cells in COP vials versus cryobags was investigated. The effect on cells post-thawing was determined by measuring its recovery, viability, proliferation, cytokine secretion, and tumor killing ability. RESULTS: A freezing rate of -1 or -5°C/min was found to be optimal for NK-92 cell storage in COP vials. DMSO as the cryoprotectant improved post-thaw proliferation, lower cell density during freezing enhanced recovery, and in contrast, higher cell density increased cytokine secretion. Ice nucleation timing on the other hand had no significant impact on NK-92 cell viability or function. Compared head-to-head, cells frozen in COP vials demonstrated superior post-thaw tumor killing activity versus cells stored in bags. CONCLUSION: This study to our knowledge provides the first comprehensive analysis of cryopreservation conditions for therapeutically relevant allogeneic cell therapy products in a clinically relevant vial, which is crucial to ensure their effectiveness upon reaching patients.
Erratum to "'Site-specific enrichment of highly sialylated N-glycans in an erythropoietin-hybrid Fc fusion protein" [Eur. J. Pharm. Biopharm. 226 (2026) 115147].
Park J, Eom D, Park CS … +8 more , Moon C, Kim S, Lee S, Lee J, Shin J, Jo Y, Lee M, Kim HH
Eur J Pharm Biopharm · 2026 Jun · PMID 42350243 · Publisher ↗
Abstract loading — click title to view on PubMed.
Hydrophobic ion pairing formed semaglutide designed for oral self-microemulsifying delivery in diabetes treatment.
Zhang Y, Cheng J, Wang H … +4 more , Zong Z, Zhang W, Shen Y, Tian Y
Eur J Pharm Biopharm · 2026 Jun · PMID 42349668 · Publisher ↗
Semaglutide (SET) is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. Although injectable formulations offer high bioavailability, they are associated with poor patient co...
Semaglutide (SET) is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes. Although injectable formulations offer high bioavailability, they are associated with poor patient compliance. In contrast, oral tablets are more convenient but suffer from limited absorption due to SET's hydrophilicity and enzymatic instability in the gastrointestinal tract. To address these challenges, we developed a hydrophobic ion pair (HIP) complex of SET and sodium docusate (SET-DOC), which was further incorporated into a self-emulsifying drug delivery system (SD@SEDDS) to facilitate oral delivery. The optimized SD@SEDDS produced a clear emulsion upon dilution, with a uniform particle size of 85.55 nm, high drug loading (2.64 mg/g), and excellent stability. In vitro transport studies using a Caco-2/HT-29 co-culture model demonstrated enhanced permeability and reduced P-glycoprotein-mediated efflux. In vivo studies in a type 2 diabetic rat model showed that SD@SEDDS significantly reduced blood glucose levels, improved lipid profiles, and exhibited good biocompatibility without observable toxicity. These findings suggested that the combination of HIP technology and SEDDS represented a promising strategy for enhancing the oral delivery efficiency of peptide drugs such as SET.
DNA network-encapsulated carnosine/ZnO nano-complexes for enhanced antibacterial efficacy and biocompatibility.
Huang KW, Huang CR, Lan KC … +2 more , Chang CH, Chen YF
Eur J Pharm Biopharm · 2026 Jun · PMID 42349667 · Publisher ↗
Developing localized, smart antibacterial systems is crucial to overcome the limitations of traditional antibiotics. Here, we report the synthesis of a DNase-responsive nano-platform, ZnO@Car@DNA-BAC, using kiwifruit-der...
Developing localized, smart antibacterial systems is crucial to overcome the limitations of traditional antibiotics. Here, we report the synthesis of a DNase-responsive nano-platform, ZnO@Car@DNA-BAC, using kiwifruit-derived genomic DNA as a sustainable scaffold. The system is engineered by cross-linking DNA with N,N'-Bis(acryloyl)cystamine (BAC) and incorporating L-carnosine (Car) functionalized ZnO nanoparticles (NPs), enabling targeted therapeutic release triggered by bacterial nucleases. Our findings reveal that while nanoparticle surface charge dictates the immediate therapeutic outcome in terms of bacterial membrane affinity, electron paramagnetic resonance (EPR) analysis confirmed ROS-mediated oxidative stress as a secondary killing mechanism. Crucially, the nanocomposite exhibited excellent biocompatibility in 3D spheroid models derived from Raw264.7 and HaCaT cells. The dual-layered encapsulation effectively mitigated the intrinsic toxicity of ZnO NPs, resulting in significantly higher IC values and preserved metabolic activity within the 3D micro-tissues compared to bare nanoparticles. Following the tissue-level safety validation, the comprehensive nano-platforms were tested in a C. elegans infection model. The results showed a significant suppression of S. aureus colonization and prolonged host survival, regardless of the initial core charge. This study provides a strategic framework for designing stimuli-responsive, charge-tunable biomaterials for precision infection control, balancing robust antibacterial performance with high tissue-level safety.
Green synthesized β-caryophyllene oxide enriched fraction-derived carbon quantum dots trigger ROS production and p53 activation in HepG2 cells.
Salve P, Bhinge S
Eur J Pharm Biopharm · 2026 Jun · PMID 42342161 · Publisher ↗
Carbon Quantum Dots (CQDs) are highly valued in the biomedical field for their intrinsic fluorescence, excellent biocompatibility, and broad range of precursor availability. This study is the first to report the preparat...
Carbon Quantum Dots (CQDs) are highly valued in the biomedical field for their intrinsic fluorescence, excellent biocompatibility, and broad range of precursor availability. This study is the first to report the preparation of CQDs using a β-caryophyllene oxide enriched fraction (BCPO-EF) isolated from Blumea eriantha DC via microwave-assisted green synthesis approach. GC-MS profiling of the isolated fraction identified the major component eluted at 25.113 min, exhibited molecular ion peak at m/z 220. In the C NMR spectrum, 15 carbon signals were observed within the δ 17.02-151.85 ppm range, while the H NMR spectrum displayed peaks between δ 0.97 and 4.98 ppm. C-O stretching bands of the epoxide ring at 1258.94 and 959.97 cm in the FTIR spectrum confirm the isolate as BCPO-EF. The structural formation of BCPO-EF-CQDs was confirmed through spectroscopic characterization. Absorption at 257 nm reflects C=C conjugation of CQDs core. BCPO-EF-CQDs cytotoxic effects on HepG2 cells were measured using the MTT cytotoxicity assay, lactate dehydrogenase (LDH) assay, apoptosis assessment, p53-MDM2 expression, and intracellular reactive oxygen species (ROS) assessment. BCPO-EF-CQDs exhibited 27.15% photoluminescence quantum yield (PLQY) and spherical particles of 3.56-8.44 nm. The IC value of BCPO-EF-CQDs was calculated to be 47.80 μg mL on HepG2 cells. Flow cytometry detected 56.70% apoptosis, ROS levels increased by 5.057-fold and Western blot showed p53 and MDM2 upregulated 11.12- and 3.68-fold, respectively in HepG2 cells following BCPO-EF-CQDs treatment. The present results confirm ROS-mediated p53 activation by BCPO-EF-CQDs in HepG2 hepatocellular carcinoma cells, warranting further investigation.
Novel approach for direct drug delivery to the central nervous system via intratympanic administration.
Saito M, Sano N, Nakayama S … +3 more , Yokoyama Y, Takeba N, Torimoto N
Eur J Pharm Biopharm · 2026 Jun · PMID 42342160 · Publisher ↗
Therapeutic drugs for central nervous system (CNS) diseases need to reach CNS tissues. However, the blood-brain barrier often limits their therapeutic effects. To address this issue, highly invasive drug administration r...
Therapeutic drugs for central nervous system (CNS) diseases need to reach CNS tissues. However, the blood-brain barrier often limits their therapeutic effects. To address this issue, highly invasive drug administration routes, such as intracerebroventricular or intrathecal administration, can be used. In addition, intranasal (i.n.) administration is increasingly being recognized as a non-invasive route, although its application in humans is limited. Hence, we explored intratympanic (i.t.) administration as a novel, minimally invasive route for direct drug delivery to the CNS. The aim of this study was to develop a new administration route that enables efficient and comprehensive evaluation of CNS drug transport by employing cassette dosing. Using this approach, we assessed multiple low- and high-permeability drugs concurrently in rodents and non-human primates. Pharmacokinetics were evaluated in cerebrospinal fluid (CSF) and brain tissues to investigate the potential for enhanced CNS penetration. Furthermore, the effects of cetirizine, a second-generation histamine receptor antagonist, on spontaneous locomotor activity were examined following i.t. and intravenous (i.v.) administration. I.t. of low-permeable drugs such as cetirizine markedly increased their penetration into CSF and brain in both rats and monkeys. Pharmacologically, i.t. of cetirizine significantly decreased spontaneous locomotor activity in rats, whereas such effects were not observed following i.v.. This study demonstrates that i.t. may serve as a promising route (Ear-to-Brain) for treating neurodegenerative diseases that currently lack effective treatment options.
Hyaluronic acid and PEA-based Rutin-loaded nanoparticles as new cardioprotective tool against anthracycline-induced cardiotoxicity.
Serri C, Quagliariello V, Pio di Cagno M … +4 more , Giunchedi P, Rassu G, Maurea N, Gavini E
Eur J Pharm Biopharm · 2026 Jun · PMID 42342159 · Publisher ↗
A dual cardioprotective strategy was developed using lipid-polymer hybrid nanoparticles co-encapsulating rutin and palmitoylethanolamide (PEA), with or without hyaluronic acid (HA). This approach may enhance cardioprotec...
A dual cardioprotective strategy was developed using lipid-polymer hybrid nanoparticles co-encapsulating rutin and palmitoylethanolamide (PEA), with or without hyaluronic acid (HA). This approach may enhance cardioprotection by improving the delivery of rutin, an agent with strong antioxidant and anti-inflammatory effects whose clinical application is constrained by poor solubility and low bioavailability. PEA, known for modulating the endocannabinoid system and inhibiting NLRP3 inflammasome activation, offers a complementary mechanism to reduce inflammation and oxidative stress. The LPNs were prepared via nanoprecipitation technique. The LPNs lacking HA exhibited an average size ∼171 nm, while HA-based LPNs displayed larger sizes ∼247 nm, accompanied by negative zeta potentials (from -20.13 to -29.95 mV) and surface hydrophilicity attributable to HA. Despite these variations, drug content and encapsulation efficiencies remained comparable between formulations. In vitro release and permeation (PermeaPad®) experiments demonstrated formulation-dependent differences in rutin delivery. Notably, HA and PEA-based LPNs significantly protected cardiomyocytes from DOXO toxicity, evidenced by decreased apoptosis, caspase activation, and LDH release, while upregulating protective proteins (Nrf2, SIRT1) and downregulating inflammatory mediators (NLRP3, MyD88, IL-1β, IL-6). These findings support the potential of HA and PEA-based LPNs as a targeted strategy to preserve anticancer efficacy while reducing DOXO-associated cardiotoxicity.
Iontophoretic-assisted wound-healing using azithromycin and nanoparticulate magnesium oxide embedded fiber coated films.
Arshad MS, Mushtaq S, Zafar S … +9 more , Rana SJ, Chohan TA, Abbas K, Rajput AW, Benziane R, Iqbal H, Onaiwu E, Fei D, Ahmad Z
Eur J Pharm Biopharm · 2026 Jun · PMID 42336001 · Publisher ↗
The present study aimed to demonstrate iontophoretic-assisted wound healing using azithromycin and magnesium oxide (MgO) particulate embedded fibers coated films. The formulations were prepared by electrospinning techniq...
The present study aimed to demonstrate iontophoretic-assisted wound healing using azithromycin and magnesium oxide (MgO) particulate embedded fibers coated films. The formulations were prepared by electrospinning technique and evaluated for physicochemical features, thermal analysis, in vitro drug release, in vitro antibiofilm and in vivo antibiofilm studies. Nano-sized MgO particles and azithromycin composite fibers displayed acceptable physicochemical properties and a smooth-surfaced interconnected network. Differential scanning calorimetry analysis suggested relatively reduced crystallinity of azithromycin upon incorporation into the polymeric matrix. During in vitro study, prepared formulations released > 95% azithromycin within 45 min exhibiting first order kinetics. Drug loaded formulations showed significantly (p value < 0.05) higher reduction in the Staphylococcus aureus (S. aureus) biomass during in vitro study when compared to the pure drug aqueous suspension. Inclusion of the metal oxide nanoparticles into the drug loaded fibers led to a significantly higher reduction in the biomass than the azithromycin alone incorporated counterparts. During in vivo antibiofilm study, iontophoresis mediated delivery of azithromycin from composite fibers resulted in a rapid reduction in the biomass of S. aureus from infected skin wounds and complete regeneration of epidermis and dermis after an 8-days treatment. It was concluded that iontophoretic delivery of azithromycin from the drug and MgO nanoparticle loaded polymeric fibers can be used to treat S. aureus biofilm contaminated wounds.
Development and clinical evaluation of a nanoemulsion for buccal delivery of cannabis extract in refractory chronic pain.
Spirito A, Provenzano R, Vitiello A … +9 more , Di Spirito NA, Izzo L, Lombardi A, Maiolino P, Pane C, Ungaro F, Saccà F, d'Angelo I, Miro A
Eur J Pharm Biopharm · 2026 Jun · PMID 42336000 · Publisher ↗
Cannabinoid-based therapies have gained increasing attention for the management of chronic and treatment-resistant pain, although their clinical application is limited by the poor aqueous solubility and variable bioavail...
Cannabinoid-based therapies have gained increasing attention for the management of chronic and treatment-resistant pain, although their clinical application is limited by the poor aqueous solubility and variable bioavailability of Δ9-tetrahydrocannabinol (THC). In this study, we developed and characterized a nanoemulsion (THC-NE) for buccal administration of a Cannabis sativa L. extract (Bedrocan®), with the aim of improving solubility, stability and bioavailability. The optimized formulation, composed of pharmaceutically acceptable excipients, showed a narrow droplet size distribution (DH ≈ 73 nm, PDI ≈ 0.2), a THC content consistent with the theoretical value (3.53 ± 0.56 mg/mL), and good physicochemical stability at 4°C for at least 90 days. The formulation maintained its properties upon extensive dilution in simulated buccal fluids and after spray nebulization, supporting its suitability for oromucosal delivery. In vitro release studies confirmed sustained THC release from THC-NE, whereas negligible release was observed from the oil extract, highlighting the role of nanoformulation in enhancing solubilization and controlled release. An observational study was conducted in 18 patients with chronic pain unresponsive to standard treatments. After a median follow-up of 189 days, mean pain scores (NRS) decreased significantly from 8.6 ± 0.9 to 5.4 ± 2.8 (p < 0.001), with 83% of patients achieving a ≥ 20% reduction. Among responders, the mean NRS decreased by 45% and treatment persistence was found to be high, with 64% of patients still remaining under therapy after six months. A total of 17 adverse events were reported in 11 patients, most of which were mild to moderate and transient. Additionally, treatment interruption occurred in three patients due to adverse events, in other three owing to limited efficacy and in two for logistical reasons. Overall, these findings indicate that buccal administration of THC-NE represents a promising patient-friendly approach for cannabis-based therapy, offering improved solubility, controlled release and meaningful clinical benefit in patients with refractory chronic pain.
Influence of simulated tear flow on ocular penetration of transfersomes.
Barbalho GN, Brugger S, Gratieri T … +3 more , Keck CM, Rupenthal ID, Agarwal P
Eur J Pharm Biopharm · 2026 Jun · PMID 42324048 · Publisher ↗
Transfersomes are deformable lipid vesicles extensively evaluated for transdermal drug delivery. However, the ocular penetration mechanism of transfersomes is poorly understood as the effect of tear flow, which by alteri...
Transfersomes are deformable lipid vesicles extensively evaluated for transdermal drug delivery. However, the ocular penetration mechanism of transfersomes is poorly understood as the effect of tear flow, which by altering osmotic gradients across ocular tissues can influence transfersome penetration, has not been evaluated before. Hence, this study investigated the impact of simulated tear flow (STF) on the ocular distribution of curcumin-loaded transfersomes. Transfersome penetration was evaluated ex vivo under static (no STF) and dynamic (with STF) conditions and the total amount penetrated (TAP) and the maximal penetration depth (MPD) in corneal and conjunctival tissues were semi-quantitatively evaluated. Corneal distribution of transfersomes was considerably altered in the dynamic model. Drug redistribution due to STF reduced TAP in the central cornea while increasing it in the peripheral cornea. Surprisingly, corneal MPD was significantly higher with STF, likely due to surface dehydration in the absence of STF. Meanwhile, STF reduced both TAP and MPD in the bulbar conjunctiva, although no significant difference was observed in the tarsal conjunctiva. These findings provide a mechanistic insight into ocular transfersome penetration and suggest that tear flow compromise, as observed in ocular surface disorders, may influence drug bioavailability by altering precorneal distribution and surface dehydration.
Model-based analysis of nanocarrier-mediated transdermal drug delivery with coated microneedles.
Benington B, Zhan W
Eur J Pharm Biopharm · 2026 Jun · PMID 42323148 · Publisher ↗
Coated microneedles represent a promising strategy to overcome the barrier of the stratum corneum in transdermal delivery, enabling direct administration of drugs into viable skin tissues and systemic circulation. Howeve...
Coated microneedles represent a promising strategy to overcome the barrier of the stratum corneum in transdermal delivery, enabling direct administration of drugs into viable skin tissues and systemic circulation. However, the delivery performance to different skin layers and the blood circulation depend strongly on the characteristics of the drug delivery system, which can vary considerably. In this study, a mathematical model incorporating a reconstructed skin structure with realistic anatomical features is developed to investigate how key, practically controllable parameters influence dynamic drug transport and accumulation within each homogeneous, isotropic skin layer and systemic blood. In particular, distributed models based on a set of convection-diffusion-reaction equations are employed to describe drug transport between the microneedle and multiple skin layers, whereas the coupled kinetic models are used to simulate drug transport within the blood compartments. The skin model consists of the stratum corneum (15 μm), viable epidermis (100 μm), papillary dermis (350 μm), and reticular dermis (800 μm). This study specifically examines drug transport through the transepidermal pathway, with appendageal transport neglected. The results confirm the capability of coated microneedles to effectively deliver nanocarrier-encapsulated drugs to both local tissues and systemic circulation. Drug concentrations generally decrease with increasing tissue depth, and delivery outcomes differ markedly among tissue compartments. Importantly, each skin layer responds differently to variations in nanocarrier and coating properties. Parameters such as nanocarrier diffusivity in the coating layer and skin tissues, interfacial transfer rate, transvascular permeability, coating thickness, and drug release kinetics significantly affect drug distribution. Some factors enhance systemic exposure at the expense of skin retention, whereas others favour local accumulation while limiting systemic transport. These findings highlight the importance of parameter optimisation according to the intended therapeutic objective, whether targeting specific skin layers or systemic circulation. Overall, this study provides mechanistic insights that support the rational design and advancement of coated microneedle-based drug delivery systems for enhanced efficacy in transdermal therapy.
From candidate ranking to lead identification - Hydrophobic interaction chromatography, PAIA, and Structure-Based calculations for hydrophobicity determination during developability assessment of mAbs and a mAb-Derived fusion protein.
Helbig C, Arsiccio A, Schuster G … +2 more , Hawe A, Menzen T
Eur J Pharm Biopharm · 2026 Jun · PMID 42323147 · Publisher ↗
Antibody therapeutics have gained critical relevance in the treatment of numerous health conditions, yet their development is resource-intensive and bears a non-negligible failure risk. Consequently, developability asses...
Antibody therapeutics have gained critical relevance in the treatment of numerous health conditions, yet their development is resource-intensive and bears a non-negligible failure risk. Consequently, developability assessment to predict a protein's likeliness to evolve into an approved drug has become a pivotal measure. Surface hydrophobicity is a crucial developability feature because of its relation to self-interaction and aggregation. In our study, we determined the hydrophobicity of 21 antibodies and one antibody-derived fusion protein by hydrophobic interaction chromatography (HIC), the emerging PAIA assay, and structure-based calculations. We derived data analysis concepts for PAIA and calculated surface descriptors by taking well-established HIC as reference. Based on these concepts and considering each technique's capabilities and limitations, we deduce how HIC, PAIA, and surface descriptors for hydrophobicity can efficiently be combined throughout the different developability assessment stages to meet material availability and required throughput and characterization depth. For discovery and early development, we illustrate the definition of in silico thresholds to identify low-risk candidates and reduce the initial candidate pool. We then show how data from 384-well plate-based PAIA screening can be used for the classification into low-, medium-, and high-hydrophobicity molecules, followed by the high-resolution hydrophobicity ranking of final lead candidate(s) by HIC.
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