European Journal Of Pharmaceutics And Biopharmaceutics[JOURNAL]
Sun
200 papers
Development and biological evaluation of new nano copolymer-drug composites designed for selective liver cancer treatment.
Kareem AA, Habeeb TZ, Al-Ghanimi BK … +2 more , Abbas ZM, Al-Baiati MN
Eur J Pharm Biopharm · 2026 Jun · PMID 41932555 · Publisher ↗
This study focuses on the design, synthesis, characterization, and biological evaluation of two novel nano-graft copolymer-drug composites (B3 and B4) for targeted liver cancer therapy. A new nano-graft copolymer was fir...
This study focuses on the design, synthesis, characterization, and biological evaluation of two novel nano-graft copolymer-drug composites (B3 and B4) for targeted liver cancer therapy. A new nano-graft copolymer was first synthesized via the reaction of phthalic anhydride with glycerol, followed by conversion to its acid chloride derivative (B2). This intermediate was successfully used to graft the therapeutic agent's ampicillin (B3) and 4-aminoantipyrine (B4). Structural confirmation of the grafted composites was achieved using FT-IR, 1H NMR, and 13C NMR spectroscopy, which verified the formation of amide bonds and the successful conjugation of the drugs to the polymer backbone. Molecular docking studies using PyRx and Biovia software revealed strong binding affinities of B3 and B4 to the liver-cancer-associated protein 1JNX, facilitated by multiple stabilizing interactions including hydrogen bonds, π-π stacking, π-alkyl interactions, and van der Waals forces with key amino acid residues. *In vitro* cytotoxicity assessment via MTT assay demonstrated potent, concentration-dependent inhibition of HEp-2 liver cancer cell proliferation, with IC values of 38.245 µg/mL for B3 and 49.551 µg/mL for B4. Microscopic analysis further confirmed significant morphological changes and cell death after treatment. In conclusion, the synthesized nano copolymer-drug composites show promising selective anticancer activity and biocompatibility, supporting further *in vivo* investigations.
Investigation of baicalin, baicalein and low-dose sulfasalazine for orocecal transit time determination in saliva and plasma.
Senekowitsch S, Link NA, Wildgrube T … +4 more , Schick P, Engeli S, Weitschies W, Grimm M
Eur J Pharm Biopharm · 2026 Jun · PMID 41932554 · Publisher ↗
The application of high-dose sulfasalazine (≥500 mg) followed by plasma or salivary sampling represents an established method for orocecal transit time determination. In the present study, we aimed to establish an altern...
The application of high-dose sulfasalazine (≥500 mg) followed by plasma or salivary sampling represents an established method for orocecal transit time determination. In the present study, we aimed to establish an alternative procedure. For this, we investigated.following the oral ingestion of low-dose sulfasalazine (50 mg) and 400 mg baicalin. Furthermore, in a second study arm 400 mg baicalein were applied together with 50 mg sulfasalazine to enhance the understanding of the oral pharmacokinetics and conversion of baicalin and baicalein. The oral application of baicalein led to an onset of plasma concentration that was substantially earlier than that of sulfapyridine. In contrast, the plasma appearance times of baicalin after oral baicalin administration was not statistically significant different from sulfapyridine plasma appearance time. However, baicalin was not secreted into saliva. Low-dose sulfasalazine proved to be a reliable salivary marker for the determination of the orocecal transit time, like already reported for high dosages. The correlation between plasma and salivary concentrations and appearance times was excellent. However, there was a statistically significant difference between sulfapyridine plasma and saliva appearance time, mainly attributable to the lower salivary sulfapyridine concentrations taking slightly more time to reach the threshold defined as appearance. Hence, it is necessary to consider the generally lower salivary sulfapyridine concentrations in appearance time determination. As this procedure only uses minimal dosages (1/10 of the lowest therapeutic dosage), the risk for side effects is reduced. Taking into consideration that the possibility for saliva sampling enables a non-invasive procedure without the need for specialized personal, this approach represents an easy to use method for studies investigating orocecal transit times.
Low-cost particulate matter sensors for real-time spatiotemporal detection of pharmaceutical dust in containment.
Küllmar H, Schöler M, Braunschweig KU … +1 more , Leopold CS
Eur J Pharm Biopharm · 2026 Jun · PMID 41905615 · Publisher ↗
Highly potent active pharmaceutical ingredients pose a risk with regard to dustiness and spatial distribution of dust in the manufacture of pharmaceuticals. Traditional filter-based methods for dust investigations, for e...
Highly potent active pharmaceutical ingredients pose a risk with regard to dustiness and spatial distribution of dust in the manufacture of pharmaceuticals. Traditional filter-based methods for dust investigations, for example based on IOM samplers have several disadvantages, such as the gravimetrical or wet chemical analysis of the collected samples, neither allowing the detection of airborne dust concentrations in real-time, nor time-resolved. Therefore, a recently developed chamber setup was equipped with low-cost particulate matter sensors to investigate their feasibility to detect and visualize the spatiotemporal distribution of pharmaceutical dusts in real-time. Experiments with the surrogate substance acetaminophen revealed that with a suitable adjustment of the atomization parameters, reproducible dust concentrations and the spatiotemporal dust distribution within the chamber setup were detectable with the sensors in real-time. Based on these results, lactose as a typical excipient in tableting blends for direct compression and a binary powder blend of acetaminophen and lactose were also investigated. The binary blend as well as plain lactose showed a reduced dustiness when compared to plain acetaminophen, indicating particle interactions between both substances which influence their tendency to become airborne. In conclusion, the particulate matter sensors allow investigations of spatiotemporal dust distributions in real-time.
Pyrogenicity of phage active pharmaceutical ingredients used for personalized therapy in Belgium.
Willocx M, Pirnay JP, Merabishvili M … +5 more , Laurent F, Clouet S, Lavigne R, Ceyssens PJ, Vanhee C
Eur J Pharm Biopharm · 2026 Jun · PMID 41903826 · Publisher ↗
The assessment of pyrogenicity is critical for phage-based therapeutic products, especially when administered intravenously. However, current standard endotoxin tests, such as the Limulus Amoebocyte Lysate (LAL) and the...
The assessment of pyrogenicity is critical for phage-based therapeutic products, especially when administered intravenously. However, current standard endotoxin tests, such as the Limulus Amoebocyte Lysate (LAL) and the recombinant Factor C (rFC) assay, capture only part of their immune-activating potential. Here, we compared the LAL test, the rFC assay, and the human cell-based Monocyte Activation Test (MAT) to evaluate the pyrogenic profile of phage active pharmaceutical ingredients (pAPIs). While LAL and rFC are rapid and cost-effective, MAT provides unique physiological relevance by capturing immune responses to both endotoxins and non-endotoxin pyrogens (NEPs), as well as potential interactions between phages and the human immune system. This study provides a first insight into the pyrogenic activity of pAPIs as perceived by human immune cells and highlights the complementary roles of endotoxin tests and MAT in ensuring product safety. The tested pAPIs generally exhibited low pyrogenicity, with most batches below 1000 EU/mL. Based on our experience, we propose a practical two-tiered quality control strategy using rFC as an initial screening tool for rapid and cost-effective endotoxin quantification, and MAT as a complement to assess pyrogenic potential as perceived by the human immune system. Importantly, MAT is not intended to overrule endotoxin detection by rFC, but rather to support the interpretation of complex pyrogenic signals. This approach provides a more physiologically relevant and comprehensive view of pyrogenicity, while supporting ethical testing practices aligned with the 3Rs principles (Replacement, Reduction, and Refinement of animal use).
Design and optimization of the surfactant mixture ratio for oleic acid-based ophthalmic nanoemulsions prepared by the HPH technology - feasibility study for clotrimazole as a model drug.
Gawin-Mikołajewicz A, Malec KH, Marciniak DM … +8 more , Dołowacka-Jóźwiak A, Piątkowska EC, Brożyna M, Junka AF, Górniak AD, Polowczyk I, Benkowska-Biernacka D, Karolewicz BL
Eur J Pharm Biopharm · 2026 Jun · PMID 41903825 · Publisher ↗
Developing ophthalmic nanoemulsions is a complex process that requires the selection of appropriate pharmaceutical excipients and optimal parameters of the technological process to achieve formulations with desirable phy...
Developing ophthalmic nanoemulsions is a complex process that requires the selection of appropriate pharmaceutical excipients and optimal parameters of the technological process to achieve formulations with desirable physicochemical properties. To develop appropriate preparations, a design of experiments was conceptualized. Varying concentrations of the surfactants (2 - 6 %) and cosurfactants (0 - 6 %) were used in nanoemulsions based on oleic acid (13 %) that were prepared under constant conditions of high-pressure homogenization technology (3 cycles, 1000 Bar). After composition optimization, the optimal concentration of the surfactants (Kolliphor EL 6 % and Tween 80 5 %) and cosurfactants (propylene glycol 2 %, PEG 200 4 %, triacetin 6 %) was selected. Utilising a developed model, clotrimazole-loaded nanoemulsions with monomodal droplet size distribution were prepared, with the average droplet diameters in the range of 88.53 - 97.06 nm and PDI values 0.080 - 0.117. After physicochemical assessment, nanoemulsion NE4_KOL6_PG2 was selected for further studies, with the highest stability, optimal physicochemical properties, and shelf-life estimation parameter at a level higher than 5 months. The release rate of clotrimazole (CLT) from the nanoemulsion NE4_KOL6_PG2 (T = 9.4 h) was significantly higher than in the case of the 1 % CLT oily solution in castor oil (T = 32.6 h). In the in vitro study, the prepared formulation obtained the MIC value 0.008 % (0.08 mg/ml) against C. albicans ATCC 10231. In the model with Galleria mellonella larvae, formulation did not affect larval survival within six days. This study demonstrated the usefulness of the obtained optimization for scalable manufacturing of stable CLT-loaded nanoemulsions with the required properties for ophthalmic use.
Nose-to-Brain delivery of genistein-loaded peppermint lipid nanocapsules for neuroprotection against Alzheimer's Disease: Formulation, Characterization, pharmacokinetic and Pharmacodynamic studies.
Labib MS, Abd-Allah H, Bazan LS … +2 more , Ibrahim HM, Abdel-Mottaleb MMA
Eur J Pharm Biopharm · 2026 Jun · PMID 41881284 · Publisher ↗
Lipid nanocapsules (LNC) are promising nanocarriers that have known mucus permeation enhancement properties, this makes them suitable for intranasal administration. They could act as potential nose-to-brain carriers for...
Lipid nanocapsules (LNC) are promising nanocarriers that have known mucus permeation enhancement properties, this makes them suitable for intranasal administration. They could act as potential nose-to-brain carriers for drugs like genistein with poor aqueous solubility and extensive metabolism, making them reach the brain in effective concentrations. This study was conducted to observe the effects of different essential oils (peppermint, lavender, and eucalyptus essential oils) on LNC characteristics including particle size, polydispersity index, and zeta potential. The optimized genistein-loaded peppermint LNC experienced a nearly full in-vitro release in 10 h. Transmission electron microscope, differential scanning calorimetry, and Fourier-transform infrared spectroscopy ensured the successful preparation of this formulation. In-vivo pharmacokinetic study revealed that the optimized LNC had better relative bioavailability than drug suspension by 60% with earlier T at 30 min and C of 23.17 ± 1.5 µg/g brain tissue. Pharmacodynamic assessment in AlCl-induced Alzheimer's disease in rats showed that the optimized LNC preserved the spatial and reference memory in Morris water maze test. Biochemical analyses confirmed the enhanced oxidative defense (increased superoxide dismutase, reduced glutathione, and decreased malondialdehyde) and the inhibition of acetylcholinesterase enzyme. Histopathological examination showed preserved neuronal structure in the hippocampal brain region. Genistein-loaded peppermint LNC were able to have neuroprotective effects, making the intranasal LNC formulation a promising candidate for the neuroprotection against Alzheimer's disease.
Cryomilling of freeze dried low-Tg sugar glasses: A versatile method to prepare inhalable dry powder formulations.
Jansen EM, Posthumus SAE, Chan MKT … +4 more , Beertema M, Mulia KF, Frijlink HW, Hinrichs WLJ
Eur J Pharm Biopharm · 2026 Jun · PMID 41876048 · Publisher ↗
Pulmonary delivery may offer significant advantages for the administration of certain biologics, but its success relies on the development of dry powder formulations that are both stable and respirable. Low-glass transit...
Pulmonary delivery may offer significant advantages for the administration of certain biologics, but its success relies on the development of dry powder formulations that are both stable and respirable. Low-glass transition temperature (Tg) sugars are widely used as stabilizing excipients, yet their application in pulmonary formulations is limited by poor physical stability during conventional processes such as spray drying or jet milling. These methods generate heat that can exceed the Tg, causing crystallization and loss of stabilizing properties. Cryomilling provides a potential solution by milling freeze dried cakes under cryogenic conditions. In this study, freeze dried sucrose, maltose, isomalt, trehalose, and lactose were cryomilled for 3, 5, 7, or 9 cycles without or with either leucine or trileucine. Physicochemical properties were assessed using X-ray powder diffraction (XRPD), modulated differential scanning calorimetry (mDSC), and dynamic vapor sorption (DVS). Furthermore, the primary particle size and the particle size and dispersion efficiency from the Cyclops DPI were analyzed by laser diffraction, while aerodynamic performance of the cryomilled dry powder formulations was measured using cascade impaction analysis. The number of cryomilling cycles did not affect primary particle size of any of the cryomilled formulations. Furthermore, sucrose, maltose, isomalt and lactose cryomilled with either 4% leucine or trileucine demonstrated superior dispersibility from the Cyclops DPI compared with formulations containing no excipient. Cascade impaction analysis confirmed that cryomilling each of the 5 freeze dried sugars with 4% trileucine achieved aerodynamic characteristics suitable for deep lung deposition. In conclusion, cryomilling of freeze dried low Tg sugars with 4% trileucine enables the production of inhalable powders from low-Tg sugars with optimal dispersibility and pulmonary performance. This approach may provide a foundation for future investigations into pulmonary delivery of biologics.
Emerging technologies and scientific advances in lyophilization of pharmaceuticals: insights from the 2025 freeze-drying of pharmaceuticals & biologicals conference.
Richert E, Winter G, Friess W
Eur J Pharm Biopharm · 2026 Jun · PMID 41871702 · Publisher ↗
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Impact of post approval quantitative changes in excipient composition on nitrosamine formation: De-risking strategy.
Charoo NA, Untoo SA, Rahman Z
Eur J Pharm Biopharm · 2026 Jun · PMID 41871701 · Publisher ↗
Between 2018 and 2021, losartan was the most often recalled product (24% of total recalls) followed by metformin tablets (19% of total recalls) due to the presence of nitrosamine impurities. The objective of this work is...
Between 2018 and 2021, losartan was the most often recalled product (24% of total recalls) followed by metformin tablets (19% of total recalls) due to the presence of nitrosamine impurities. The objective of this work is to analyse the de-risking method in terms of reducing nitrosamine generation and establishing nitrite specifications in excipients. In light of these recalls, we simulated the influence of post-approval level 1 and level 2 changes in excipient compositions on nitrosamine formation in metformin SR (sustained release) and losartan film coated tablets. Furthermore, we investigated the de-risking approach in terms of reducing nitrosamine formation and establishing nitrite specifications in excipients. Level 1 changes in excipient composition resulted in no discernible increase in nitrosamine impurities for both metformin SR and losartan film coated tablets. On the other hand, level 2 changes resulted in more than 7% and 18% increase in nitrosamine levels in metformin SR and losartan film coated tablets, respectively. In fact, level 2 changes could cause nitrosamine impurities to exceed the AI (acceptable intake) limits. When low-nitrite level (LNL) excipients were employed, level 2 changes resulted in no significant increase in nitrosamine formation from their original values. Finally, specifications for nitrite in excipients were established. Selecting formulation excipients with LNLs is critical for risk mitigation as was demonstrated in this study. To continue enjoying the regulatory flexibility in terms of reducing post approval variation submissions, it is paramount to assess the impact of nitrite load of excipients on the total nitrosamine burden of the product during product development.
Human photoaging skin models for the efficacy evaluation of anti-aging ingredients: Advances on clinical and ex vivo studies.
Jesus A, Silva JP, Cidade H … +3 more , Cruz MT, Sousa E, Almeida IF
Eur J Pharm Biopharm · 2026 Jun · PMID 41866002 · Publisher ↗
Solar radiation impacts the skin's biological processes, leading to premature aging. Accurately identifying and evaluating these effects in humans through tissue-based models is essential for advancing anti-aging researc...
Solar radiation impacts the skin's biological processes, leading to premature aging. Accurately identifying and evaluating these effects in humans through tissue-based models is essential for advancing anti-aging research and validating cosmetic ingredients claims. However, the existing literature remains highly fragmented, hindering the identification of suitable photoaging skin models and knowledge gaps. This work provides a comprehensive and up-to-date review of human (clinical and ex vivo) photoaging skin models used to assess the anti-aging efficacy of cosmetic ingredients, paving the way for the development of more advanced models for this purpose. A total of 43 studies using human skin (24 clinical and 19 ex vivo studies) were identified and curated. Clinical studies capture integrated physiological responses, in their majority associated with the improvement of clinical manifestations, whereas ex vivo models enable controlled mechanistic assessments of cellular and molecular changes. The key biomarkers evaluated in these studies encompass the main hallmarks of skin aging, including inflammation, oxidative stress, cellular senescence, and structural alterations. In recent years, the assessment of photo-induced alterations in skin fibers and oxidation products has improved considerably due to the advances in the spectroscopic techniques in clinical studies. Despite these advances, variability in exposure conditions, biomarker selection, and phototype representation thwarts deeply cross-study comparisons. Future progress should focus on incorporating a broader range of Fitzpatrick phototypes, optimising irradiation conditions to approximate to the chronic solar exposure and integrating new biomarkers such as advanced glycation end-products and immunosuppressive indicators. The implementation of emerging technologies, such as skin-on-a-chip systems, and microfluidics, could enhance physiological relevance and reproducibility. Overall, this review identifies the key findings, highlighting strengths and limitations of the models, and future priorities towards the development and implementation of accurate human skin models for assessing anti-aging efficacy.
Supersaturated SNEDDS for enhancing the bioavailability of lapatinib ditosylate: A mechanistic approach to bridge the solubilization-absorption gap.
Singh N, Pal A, Kumar A … +4 more , Kumari M, Zapadia B, Roy SK, Datta P
Eur J Pharm Biopharm · 2026 Jun · PMID 41866001 · Publisher ↗
A supersaturated self-nanoemulsifying drug delivery system (superSNEDDS) is investigated to enhance the oral bioavailability of lapatinib ditosylate (LPT), a BCS class II kinase inhibitor with ∼24% systemic availability....
A supersaturated self-nanoemulsifying drug delivery system (superSNEDDS) is investigated to enhance the oral bioavailability of lapatinib ditosylate (LPT), a BCS class II kinase inhibitor with ∼24% systemic availability. An integrative evaluation encompassing in-vitro lipolysis, dissolution-digestion coupling, Caco-2 permeability, and in-vivo pharmacokinetics was undertaken to mechanistically address the solubilization-absorption gap, a key barrier limiting the performance of solubilization-enhancing formulations. Especially for LPT, such correlative studies have not been reported earlier. Following a comprehensive excipients screening, the superSNEDDS was formulated with Phosal® 53 MCT, Labrasol® ALF, Transcutol® HP, and PVP K-30 (PhLaT-superSNEDDS), and 40 mg/g of LPT was dissolved in it (LPT-PhLaT-superSNEDDS). Two-stage in vitro dissolution was performed using biorelevant media simulating gastric (FaSSGF, pH 1.6), and intestinal conditions (FaSSIF). In the gastric phase (15 min), LPT-PhLaT-superSNEDDS achieved 88 ± 3% cumulative drug dissolution (mean ± SD, n = 3), which was approximately 5-fold higher (p < 0.0001) than LPT-suspension (17 ± 1%). It continued to maintain 80% of the drug in a supersaturated state for more than 120 min after the intestinal transition condition. Following lipid digestion for 30 min, LPT-PhLaT-superSNEDDS formulation achieved 8-fold (p < 0.0001) higher aqueous solubility than LPT-suspension. In Caco-2 cell lines, P of 1.87 × 10 cm/s was obtained, significantly higher than LPT-suspension (6.55 × 10 cm/s) concurrently with a 1.5 times reduction in the efflux ratio of LPT-PhLaT-superSNEDDS compared to the LPT-suspension. Wistar rats showed a 5.3 times (p < 0.0001) higher C (1220 ± 140 ng/mL) from LPT-PhLaT-superSNEDDS formulation than LPT-suspension (230 ± 80 ng/mL) and a 5 times higher (p < 0.0001) AUC (12,883 ± 78 ng · h/mL was compared to 2600 ± 116 ng · h/mL). A strong positive correlation was observed between P and C (R = 1, p < 0.0008) or P and AUC (R = 0.926) as well as between dissolution and C (R = 0.999, p < 0.018) and AUC (R = 0.939). Results lead to the conclusion that the rationale design of delivery systems with mechanistic characterization of delivery systems addressing the supersaturation-permeability balance, and augments the oral bioavailability of LPT, addressing critical challenges faced for novel delivery systems of BCS class II drugs.
Orodispersible tablets as delivery platform for oral administration of drug-loaded nanoparticles to paediatric patients.
Cornilă A, Iurian S, Tefas LR … +7 more , Muntean DM, Casian T, Hales D, Rus LM, Tudoran LB, Tomuță I, Porfire AS
Eur J Pharm Biopharm · 2026 Jun · PMID 41866000 · Publisher ↗
Patient-friendly solid oral dosage forms remain a rather understudied part of pharmaceutical development, particularly in paediatric patients. Thus, patients and caregivers around the world must resort to traditional app...
Patient-friendly solid oral dosage forms remain a rather understudied part of pharmaceutical development, particularly in paediatric patients. Thus, patients and caregivers around the world must resort to traditional approaches, such as liquid dosage forms or division of solid dosage forms, which can lead to inaccurate dosing and drug inactivation. To avoid these issues, as well as the swallowing problems and choking risk of conventional solid oral dosage forms, there is a need for modern, safe and effective oral dosage forms. Orodispersible tablets enhance the ease of administration for patients with deglutition difficulties, but their use is typically confined to immediate-release delivery systems. In this study, we addressed these shortcomings by developing orodispersible tablets as delivery platform for oral administration of loratadine-loaded zein-based nanostructures to paediatric patients. First, the nanostructures were freeze-dried with mannitol and maltodextrin as cryoprotectants. The resulting powders were compressed as such or mixed with different ratios of co-processed excipients for orodispersible tablets, in order to understand their compression behaviour. To ensure dose uniformity and powder homogeneity, a near infrared spectroscopic method was developed for non-destructive assessment of the API content. With the aid of the co-processed excipients and supplementary lubrication to reduce the tablet ejection stress, tablets with adequate mechanical properties and a disintegration time within the required range of 180 s were obtained from the nanostructures lyophilised with mannitol. Through this methodology, we have transformed loratadine-based nanosystems into an innovative and patient-friendly oral delivery system that meets the specific quality requirements of orodispersible pharmaceutical forms.
Integrating Quality by Design and Hansen Solubility Parameters in Preformulation of Vanillic Acid-Loaded Nanostructured Lipid Carriers (Part I).
Maher M, Abd-Allah H, S Ibrahim S … +1 more , D Mortada N
Eur J Pharm Biopharm · 2026 Jun · PMID 41864441 · Publisher ↗
Phenolic acids such as vanillic acid (VA) possess diverse pharmacological activities, however, their clinical application is hindered by poor solubility and bioavailability. In this study, a systematic quality by design...
Phenolic acids such as vanillic acid (VA) possess diverse pharmacological activities, however, their clinical application is hindered by poor solubility and bioavailability. In this study, a systematic quality by design (QbD) approach was followed to develop versatile VA-loaded nanostructured lipid carriers (NLCs). First, quality target product profile (QTPP) and critical quality attributes (CQAs) were identified, followed by a risk assessment using an Ishikawa diagram and failure mode and effect analysis (FMEA). Hansen solubility parameters and experimental solubility studies identified the optimal solid and liquid lipids for solubilizing VA, at 70:30 ratio as suggested by differential scanning calorimetry (DSC) and filter paper method. Plackett-Burman design was employed to screen eleven high-risk factors, where Pareto charts and perturbation plots identified stirring time, amounts of lipid, VA and lecithin, aqueous phase volume, stabilizer type and concentration, sonication time and on: off cycles as significant factors affecting the CQAs. The prepared NLCs displayed a wide range of particle sizes (203.6 nm to 2048 nm), a negative surface charge and a high entrapment reaching 86.35 %. These characteristics make the developed NLCs adaptable for most routes of administration and provide a practical QbD framework that can guide the development of a wide range of phenolic acid-loaded NLCs.
Bioinspired apixaban nanosuspension-loaded polymeric microneedle arrays for non-invasive transdermal delivery: a skin-friendly patch.
Abdel-Messih HA, El Zaafarany GM, Ishak RAH … +1 more , Mortada ND
Eur J Pharm Biopharm · 2026 Jun · PMID 41861921 · Publisher ↗
Apixaban (APX), an anticoagulant drug with indications in managing strokes, systemic embolism and deep vein thrombosis, has been of great interest since COVID-19 pandemic. We investigated, for the first time, the non-inv...
Apixaban (APX), an anticoagulant drug with indications in managing strokes, systemic embolism and deep vein thrombosis, has been of great interest since COVID-19 pandemic. We investigated, for the first time, the non-invasive transdermal delivery of APX nanosuspension (NS)-loaded microneedle (MN) array patches using sodium alginate (SA) and pectin polymers, to enhance its bioavailability and improve patient compliance. APX-SA-NS and APX-pectin-NS were formulated and screened using emulsification solvent evaporation technique, acquiring particle sizes of 405.25 ± 8.41 and 443.3 ± 27.31 nm, respectively, then incorporated into MN arrays, and subjected to morphological examination, texture analyses, ex vivo skin penetration/permeation and in vivo pharmacokinetic studies. APX-SA-MNs and APX-pectin-MNs visualized by various imaging techniques had fitting mechanical strength with effective skin piercing/insertion properties, reaching depths of 504 and 630 μm, respectively, adequate for transdermal drug delivery. Ex vivo experiments and in vivo pharmacokinetics revealed the superiority of SA-MNs over pectin-MNs in skin permeation with respective area under the curve values reaching 7500.03 ± 1326.31 and 2181.92 ± 777.07 ng/ml*h, compared to 4120.48 ± 148.48 ng/ml*h for the oral marketed tablet Apixatrack®. SA-MNs also exhibited exceptional prolonged mean residence times and relative bioavailability. Histopathology indicated the skin-friendly impact of SA-MNs patches, whereas, pectin-MNs showed signs of inflammation, endorsing SA superiority for APX delivery via ensuring a lower dosing frequency, enhanced drug efficacy, and increased patient compliance.
Inhibition of sebum production and pro-inflammatory mediators by QDF hydrogel reduces acne symptoms in mice model.
Wang R, Cai K, Xu T … +6 more , Luo A, Wang Y, Lai Z, Wang J, Zhao J, Nie H
Eur J Pharm Biopharm · 2026 Jun · PMID 41846039 · Publisher ↗
OBJECTIVE: This study aimed to prepare a hydrogel loaded with the "Qu Dou Formula" (QDF), a compound formula of traditional Chinese medicine (TCM) modified from Qing Shang Fang Feng Tang, and explore its potential benefi...
OBJECTIVE: This study aimed to prepare a hydrogel loaded with the "Qu Dou Formula" (QDF), a compound formula of traditional Chinese medicine (TCM) modified from Qing Shang Fang Feng Tang, and explore its potential benefits in the treatment of acne, as well as the mechanisms by which QDF inhibits sebum secretion and attenuates inflammatory responses. METHODS: QDF hydrogels were prepared from oxidized sodium alginate/carboxymethyl chitosan (OSA/CMCS) microspheres crosslinked with the chitosan quaternary ammonium salt. A composite model of acne on the backs of the mice was established, and histopathology was used to assess the effect of QDF on acne lesions. Network pharmacology was used to identify important intervention pathways and targets. In vivo experiments were performed to detect the expression of genes and proteins associated with inflammation and sebum metabolism. RESULTS: First, we successfully prepared a stable and biocompatible QDF hydrogel. Second, QDF significantly improved pathological changes in skin lesions, reduce the infiltration of inflammatory cells in the dermis and inhibit the secretion of FFA and TG. Network pharmacology suggest that QDF may exert anti-inflammatory effects through TNF, IL-6 and other targets. In addition, QDF inhibits the secretion of TLR2, MMP9 and other factors, ultimately reducing acne inflammation. CONCLUSION: In this study, a stable and biocompatible QDF hydrogel was prepared, suggesting that the QDF hydrogel can inhibit sebum secretion and inflammation through multiple pathways and multiple targets, and effectively relieve acne symptoms. This study provides new insights and directions for acne treatment.
Lipid excipients as key modulators of the apparent intestinal permeability in lipid-based formulations: Insights from Caco-2 and Caco-2/HT29-MTX models.
Bourderi-Cambon A, Fadhlaoui K, Garrait G … +4 more , Rossano M, Miolane C, Caisse P, Beyssac E
Eur J Pharm Biopharm · 2026 Jun · PMID 41833799 · Publisher ↗
Lipid-based formulations (LBFs) represent a promising strategy to improve the oral absorption of poorly soluble and poorly permeable compounds, such as BCS Class IV drug. Nevertheless, the development of lipid formulatio...
Lipid-based formulations (LBFs) represent a promising strategy to improve the oral absorption of poorly soluble and poorly permeable compounds, such as BCS Class IV drug. Nevertheless, the development of lipid formulations requires predictive in vitro models that closely mimic in vivo physiology, allowing for more reliable estimation of oral absorption. Permeability studies using culture cells monolayers can contribute to evaluate the influence of formulation components as well as the interplay between solubilisation and permeation. In this study, the cytotoxicity of ticagrelor, a BCS class IV drug, and placebo formulations was first assessed in Caco-2 cells, and selected LBFs were subsequently validated in both Caco-2 monoculture and Caco-2/HT29-MTX co-culture. The apparent permeability (Papp) was estimated using the well-established Caco-2 monoculture model and the more innovative Caco-2/HT29-MTX co-culture, which incorporates mucus secretion to better mimic the intestinal barrier. LC/MS analysis from permeability studies revealed that the apparent permeability coefficient of the pure API (1.02 × 10 cm/s for monoculture and 1.25 × 10 cm/s for co-culture) was significantly enhanced, by a factor ranging from 4.6 to 9.4 for monoculture, and from 2.1 to 6.6 for co-culture, when formulated in LBFs. The inclusion of permeation enhancers in the LBFs increased Papp values compared for LBFs without permeation enhancers. Overall, a decrease in permeability was observed in the co-culture model due to the mucus barrier, although this reduction was not statistically significant for the majority of tested formulations.
Alginate microcapsules for topical delivery of lavender essential oil: Impact of divalent crosslinkers on release, antibacterial efficacy and biocompatibility.
Kabalan Y, Bernarda H, Montané X … +8 more , Szymański T, Cywoniuk P, Rybka JD, Przysiecka Ł, Jancelewicz M, Tylkowski B, Giamberini M, Woźniak-Budych M
Eur J Pharm Biopharm · 2026 Jun · PMID 41825722 · Publisher ↗
Lavender essential oil has shown antibacterial activity against acne-associated bacteria; however, its volatility, oxidative instability, and potential skin irritation limit direct topical application. Moreover, the inco...
Lavender essential oil has shown antibacterial activity against acne-associated bacteria; however, its volatility, oxidative instability, and potential skin irritation limit direct topical application. Moreover, the incorporation of essential oils into hydrogel-based delivery systems presents formulation challenges related to nanoemulsion stability, encapsulation efficiency, and controlled release. The objective of this study was to develop and characterise alginate-based capsules containing lavender oil, crosslinked with either zinc or calcium ions, as a potential topical delivery system for acne therapy. Capsules crosslinked with zinc or calcium ions were prepared using a scalable combination of ionic gelation and nanoemulsion techniques, yielding high encapsulation efficiency (around 98 ± 0.2%). Capsules prepared with 2% alginate and 2% crosslinker exhibited spherical morphology and reproducible size. Oil-loaded capsules showed a porous internal structure and reduced mechanical stiffness compared to empty systems. Isothermal thermogravimetric analysis demonstrated improved oil retention in calcium-crosslinked formulations. Biological evaluation revealed antibacterial and anti-inflammatory activity, with distinct ion-dependent effects and formulation-specific cytocompatibility profiles. This study demonstrates that alginate-based microcapsules can serve as effective delivery systems for essential oils, enabling stabilisation, controlled release, and enhanced biological activity. The results underline the importance of crosslinker selection in balancing efficacy and safety, providing formulation-level design guidelines for the development of essential oil-based topical drug delivery systems.
Electrospun polylactic acid (PLA)/polycaprolactone (PCL) nanofibrous wound dressings incorporating caffeic acid and gentamicin for antibacterial and antibiofilm applications.
Reyhanoglu MB, Sulutas RB, Adali B … +5 more , Kaya E, Tinaz GB, Evran S, Gunduz O, Cesur S
Eur J Pharm Biopharm · 2026 Jun · PMID 41819502 · Publisher ↗
To investigate their effects on the epithelial tissue surface, caffeic acid (CA) and gentamicin (GEN) were loaded onto electrospun nanofibers formed from a polylactic acid (PLA)/polycaprolactone (PCL) combination. The mo...
To investigate their effects on the epithelial tissue surface, caffeic acid (CA) and gentamicin (GEN) were loaded onto electrospun nanofibers formed from a polylactic acid (PLA)/polycaprolactone (PCL) combination. The morphology, chemical structures, and thermal temperatures of the produced pure PLA/PCL, PLA/PCL/CA, PLA/PCL/GEN, and combined drug-loaded PLA/PCL/CA/GEN nanofiber patches were determined. SEM images demonstrate smooth surfaces for both pure and agent-loaded nanofibrous patches. Tensile test results indicate that GEN and CA, when loaded separately, exhibited good resistance to tensile forces, exhibiting similar strength values. According to the drug release results, CA release ended at 4 days, while GEN release continued until the 11th day. The antibacterial and antibiofilm activities of PLA/PCL, PLA/PCL/CA, PLA/PCL/GEN, and PLA/PCL/CA/GEN nanofiber patches against Pseudomonas aeruginosa and Staphylococcus aureus were evaluated. Results showed that PLA/PCL/CA/GEN nanofiber patches have excellent antibacterial and antibiofilm activities. This research provides an innovative perspective on the development of dual-acting wound dressings with antibacterial and anti-inflammatory properties through the use of CA and GEN. Our study supports the finding that dual-acting wound dressings are biocompatible materials that provide functionality in wound healing, and we obtained comparable findings supported by morphological, chemical, mechanical properties, in-vitro biocompatibility, and antimicrobial tests of nanofibers.
Utilizing large-scale produced exosomes in a hepatocellular carcinoma model as an antigen delivery system.
Kimiz-Gebologlu I, Kantarci AG, Oncel SS
Eur J Pharm Biopharm · 2026 Jun · PMID 41812777 · Publisher ↗
Since the discovery of exosomes, research has focused on their potential as delivery systems and immunomodulatory platforms for early diagnosis and therapy in various diseases. However, the problems related to the produc...
Since the discovery of exosomes, research has focused on their potential as delivery systems and immunomodulatory platforms for early diagnosis and therapy in various diseases. However, the problems related to the production, isolation and various loading strategies of sufficient amounts of exosomes for clinical use have not been fully resolved. In this study, the large-scale production of human monocyte cell line THP-1 which were adapted to chemically defined medium that did not contain serum and animal protein, the optimization of the ultrafiltration method, which is more suitable for large-scale exosomes during exosome isolation from cells, detailed characterization of the obtained exosomes, loading with hepatitis B antigen and testing in the established hepatocellular carcinoma model by hanging drop were carried out. THP-1 cells were successfully grown in a stirred tank bioreactor with a working volume of 1 L and exosomes were isolated in an ultrafiltration system with a flow rate of 125 rpm. Additionally, it was determined that loading 5 µg recombinant HBsAg/mL antigen into the exosomes isolated as a result of large-scale production by the co-incubation method was effective on both spheroid formation and the formed spheroid. These findings demonstrate that large-scale-produced exosomes can serve as an effective antigen delivery platform and highlight their potential application in vaccine-related strategies targeting HBV-associated hepatocellular carcinoma.
One-step synthesized NIR-responsive polydopamine nanoparticles for synergistic nitric oxide chemotherapy and photothermal therapy against multidrug-resistant bacteria.
Wang J, Wang Y, Song H … +2 more , Yang X, Zhang Y
Eur J Pharm Biopharm · 2026 Jun · PMID 41806926 · Publisher ↗
To address the global challenge of multidrug-resistant bacteria (MDRB), this study developed near-infrared (NIR)-responsive polydopamine nanoparticles (PDA NP-BNN6) that synergize nitric oxide (NO)-mediated chemotherapy...
To address the global challenge of multidrug-resistant bacteria (MDRB), this study developed near-infrared (NIR)-responsive polydopamine nanoparticles (PDA NP-BNN6) that synergize nitric oxide (NO)-mediated chemotherapy and photothermal therapy (PTT). A one-step synthesis strategy was employed to simultaneously encapsulate the NO donor BNN6 and fabricate PDA nanoparticles, achieving a high drug-loading efficiency of 35.05% while significantly simplifying the preparation process. The optimized formulation (PDA NP-BNN6-20) exhibited efficient photothermal conversion (ΔT = 23.7 °C), excellent cyclic stability, and precise NIR-triggered NO release under 808 nm irradiation. Quantitative assays demonstrated remarkable synergistic antibacterial rates of 92.54% against S. aureus and 92.03% against E. coli after 25 min of irradiation. Morphological analysis revealed severe membrane disruption under combined NO/PTT treatment, corroborating the dual-action mechanism. Additionally, the nanoparticles showed favorable hemocompatibility (hemolysis < 2%) and good colloidal stability. By integrating efficient one-step synthesis, controlled NO release, and potent photothermal activity, this work presents a streamlined and effective antibacterial nanoplatform, offering a promising proof-of-concept for localized anti-infective therapy, particularly for biofilm-associated and device-related infections.
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