Pub Date : 2025-12-27DOI: 10.1016/j.ejpb.2025.114969
Samaa Abdullah , Samar Thiab , Abeer A. Altamimi , Alaa A. Al-Masud , Meshal Marzoog Al-Sharafa , Hatim S. AlKhatib , Imad Hamadneh
{"title":"Corrigendum to “Nanogel therapy for chronic and post-surgical wounds: a bioengineered Lactoferrin–Acacia–Alginate system enhancing tissue regeneration and inflammatory resolution” [Eur. J. Pharm. Biopharm. 219 (2026) 114952]","authors":"Samaa Abdullah , Samar Thiab , Abeer A. Altamimi , Alaa A. Al-Masud , Meshal Marzoog Al-Sharafa , Hatim S. AlKhatib , Imad Hamadneh","doi":"10.1016/j.ejpb.2025.114969","DOIUrl":"10.1016/j.ejpb.2025.114969","url":null,"abstract":"","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114969"},"PeriodicalIF":4.3,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-23DOI: 10.1016/j.ejpb.2025.114979
Thomas Eason , Ellie Ponsonby-Thomas , Anna C. Pham , Shouyuan Huang , Simone Margaard Offersen , Thomas Thymann , Vanessa Zann , Malinda Salim , Ben J. Boyd
Milk-based formulations have been proposed as enabling formulations for the delivery of poorly water-soluble drugs to children due to their safety, dose versatility and ability to improve drug solubilisation through the digestion process. In this study the feasibility of using commercially available infant formula as an enabling formulation to enhance the solubilisation and oral bioavailability of clofazimine, a poorly soluble lipophilic drug, following oral administration was investigated. The solubilisation of crystalline clofazimine in digesting infant formula was assessed in vitro using synchrotron small-angle X-ray scattering. An in vivo pharmacokinetic study was then conducted to determine the oral bioavailability of a suspension of clofazimine in infant formula compared to a lipid-free aqueous suspension in both a rat and piglet animal model. Clofazimine administered in infant formula produced significantly higher plasma concentrations than the aqueous vehicle and resulted in comparable enhancements in relative oral bioavailability in both the piglet (235%) and rat animal models (256%). Results from this study demonstrated that infant formula was an effective enabling formulation, with a positive correlation between improved drug solubilisation during in vitro digestion of infant formula and enhanced in vivo drug exposure following oral administration. Infant formula therefore offers an inexpensive and scalable formulation approach for improving the bioavailability of paediatric drugs, like clofazimine, and enabling the treatment of infections in children.
{"title":"Co-administering clofazimine with infant formula enhances its oral bioavailability in rats and pigs","authors":"Thomas Eason , Ellie Ponsonby-Thomas , Anna C. Pham , Shouyuan Huang , Simone Margaard Offersen , Thomas Thymann , Vanessa Zann , Malinda Salim , Ben J. Boyd","doi":"10.1016/j.ejpb.2025.114979","DOIUrl":"10.1016/j.ejpb.2025.114979","url":null,"abstract":"<div><div>Milk-based formulations have been proposed as enabling formulations for the delivery of poorly water-soluble drugs to children due to their safety, dose versatility and ability to improve drug solubilisation through the digestion process. In this study the feasibility of using commercially available infant formula as an enabling formulation to enhance the solubilisation and oral bioavailability of clofazimine, a poorly soluble lipophilic drug, following oral administration was investigated. The solubilisation of crystalline clofazimine in digesting infant formula was assessed <em>in vitro</em> using synchrotron small-angle X-ray scattering. An <em>in vivo</em> pharmacokinetic study was then conducted to determine the oral bioavailability of a suspension of clofazimine in infant formula compared to a lipid-free aqueous suspension in both a rat and piglet animal model. Clofazimine administered in infant formula produced significantly higher plasma concentrations than the aqueous vehicle and resulted in comparable enhancements in relative oral bioavailability in both the piglet (235%) and rat animal models (256%). Results from this study demonstrated that infant formula was an effective enabling formulation, with a positive correlation between improved drug solubilisation during <em>in vitro</em> digestion of infant formula and enhanced <em>in vivo</em> drug exposure following oral administration. Infant formula therefore offers an inexpensive and scalable formulation approach for improving the bioavailability of paediatric drugs, like clofazimine, and enabling the treatment of infections in children.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114979"},"PeriodicalIF":4.3,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145833583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-22DOI: 10.1016/j.ejpb.2025.114972
Jia Deng , Jiangying Li , Yangwen Peng , Qian Dai , Ningbo Pang , Zhe Wang , Hailu Zhang , Xin Chen
Sulfasalazine (SULF) is a well-established therapeutic agent for rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but its oral absorption is limited by efflux transporters, particularly MRP2 and BCRP. Consequently, high daily doses (1–3 g) and frequent administration (three to four times daily) are required, increasing the risk of adverse effects during long-term therapy. To overcome these limitations, co-amorphous systems (CASs) of SULF with quercetin (QUE) were developed in this study. The CASs were systematically characterized using powder X-ray diffraction (PXRD), polarized light microscopy (PLM), scanning electron microscopy (SEM), and temperature-modulated differential scanning calorimetry (mDSC). The molecular-level formation mechanism was further elucidated via Fourier-transform infrared spectroscopy (FTIR) and molecular dynamics (MD) simulations. All SULF–QUE CASs exhibited glass transition temperatures around 113 °C and demonstrated sustained-release behavior, with markedly lower SULF dissolution (24.5–42.9 %) compared to the crystalline form (89.8 %) after 6 h. This reduction was attributed to the in situ formation of a dense “shell-like” recrystallized QUE surface structure resulting from its incongruent dissolution. Importantly, co-amorphous forms demonstrated enhanced oral bioavailability (1.52–2.80-fold) and prolonged Tmax (1.84–5.52-fold) compared to crystalline SULF, fulfilling the original goal of their development. Moreover, these systems exhibited satisfactory physical stability over time. Overall, the SULF–QUE CASs present a promising strategy to optimize the clinical dosage of SULF, reduce side effects, and offer a synergistic therapeutic approach for RA and IBD.
柳氮磺胺吡啶（SULF）是一种公认的治疗类风湿性关节炎（RA）和炎症性肠病（IBD）的药物，但其口服吸收受到外排转运蛋白，特别是MRP2和BCRP的限制。因此，需要每日高剂量（1-3 g）和频繁给药（每日三至四次），这增加了长期治疗期间不良反应的风险。为了克服这些限制，本研究开发了SULF与槲皮素（QUE）的共无定形体系（CASs）。采用粉末x射线衍射（PXRD）、偏振光显微镜（PLM）、扫描电镜（SEM）和温度调制差示扫描量热法（mDSC）对CASs进行了系统表征。通过傅里叶变换红外光谱（FTIR）和分子动力学（MD）模拟进一步阐明了分子水平的形成机理。所有的SULF- que CASs都表现出113 °C左右的玻璃化转变温度，并表现出缓释行为，在6 h后，SULF的溶解（24.5-42.9 %）明显低于结晶形式（89.8 %）。这种减少归因于原位形成致密的“贝壳状”再结晶QUE表面结构，这是由于其不均匀溶解造成的。重要的是，与结晶型磺胺砜相比，共无定形形式表现出更高的口服生物利用度（1.52-2.80倍）和延长的Tmax（1.84-5.52倍），实现了其开发的最初目标。此外，随着时间的推移，这些系统表现出令人满意的物理稳定性。总体而言，SULF- que CASs为优化SULF的临床剂量、减少副作用以及为RA和IBD提供协同治疗方法提供了一种有希望的策略。
{"title":"Sulfasalazine–quercetin co-amorphous systems: Sustained release behaviors and enhanced pharmacokinetics","authors":"Jia Deng , Jiangying Li , Yangwen Peng , Qian Dai , Ningbo Pang , Zhe Wang , Hailu Zhang , Xin Chen","doi":"10.1016/j.ejpb.2025.114972","DOIUrl":"10.1016/j.ejpb.2025.114972","url":null,"abstract":"<div><div>Sulfasalazine (SULF) is a well-established therapeutic agent for rheumatoid arthritis (RA) and inflammatory bowel disease (IBD), but its oral absorption is limited by efflux transporters, particularly MRP2 and BCRP. Consequently, high daily doses (1–3 g) and frequent administration (three to four times daily) are required, increasing the risk of adverse effects during long-term therapy. To overcome these limitations, co-amorphous systems (CASs) of SULF with quercetin (QUE) were developed in this study. The CASs were systematically characterized using powder X-ray diffraction (PXRD), polarized light microscopy (PLM), scanning electron microscopy (SEM), and temperature-modulated differential scanning calorimetry (mDSC). The molecular-level formation mechanism was further elucidated via Fourier-transform infrared spectroscopy (FTIR) and molecular dynamics (MD) simulations. All SULF–QUE CASs exhibited glass transition temperatures around 113 °C and demonstrated sustained-release behavior, with markedly lower SULF dissolution (24.5–42.9 %) compared to the crystalline form (89.8 %) after 6 h. This reduction was attributed to the in situ formation of a dense “shell-like” recrystallized QUE surface structure resulting from its incongruent dissolution. Importantly, co-amorphous forms demonstrated enhanced oral bioavailability (1.52–2.80-fold) and prolonged <em>T</em><sub>max</sub> (1.84–5.52-fold) compared to crystalline SULF, fulfilling the original goal of their development. Moreover, these systems exhibited satisfactory physical stability over time. Overall, the SULF–QUE CASs present a promising strategy to optimize the clinical dosage of SULF, reduce side effects, and offer a synergistic therapeutic approach for RA and IBD.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114972"},"PeriodicalIF":4.3,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145827148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-21DOI: 10.1016/j.ejpb.2025.114971
Dominique Lunter , Sascha Gorissen , Michael Herbig , Martin Hukauf , Adina Eichner
With great anticipation, the European Medicines Agency (EMA) guideline titled “Quality and Equivalence of Locally Applied, Locally Acting Cutaneous Products” officially came into effect on April 2, 2025. This regulatory document establishes the legal and scientific framework for the evaluation of generic topical medicinal products, particularly those for which systemic bioavailability is not a relevant endpoint. The guideline is designed to replace conventional clinical trials with scientifically justified alternative methodologies for demonstrating therapeutic equivalence to reference products in the context of generic marketing authorization. These methodologies include, most notably, in vitro release testing (IVRT), in vitro permeation testing (IVPT), stratum corneum sampling via tape stripping (TS), and the vasoconstriction assay for corticosteroids. Based on the draft guideline version released in 2018, preliminary experience has been gathered in recent years regarding the implementation and practical applicability of some testing parameters proposed. However, this early engagement also exposed several ambiguities and limitations in the draft guidance, prompting expectations that the finalized version would address these deficiencies and offer more comprehensive direction on the use of these methods. The present paper is intended to summarize these known limitations and critically examine selected aspects of the guideline. Thereby, it seeks to provide an informed perspective on the scope, robustness, and regulatory utility of the final guideline, and to facilitate a dialogue on its practical implementation in regulatory and industrial settings.
{"title":"Reflection paper on the APV workshop on in vitro performance testing of topically applied and topically acting substances","authors":"Dominique Lunter , Sascha Gorissen , Michael Herbig , Martin Hukauf , Adina Eichner","doi":"10.1016/j.ejpb.2025.114971","DOIUrl":"10.1016/j.ejpb.2025.114971","url":null,"abstract":"<div><div>With great anticipation, the European Medicines Agency (EMA) guideline titled <em>“Quality and Equivalence of Locally Applied, Locally Acting Cutaneous Products”</em> officially came into effect on April 2, 2025. This regulatory document establishes the legal and scientific framework for the evaluation of generic topical medicinal products, particularly those for which systemic bioavailability is not a relevant endpoint. The guideline is designed to replace conventional clinical trials with scientifically justified alternative methodologies for demonstrating therapeutic equivalence to reference products in the context of generic marketing authorization. These methodologies include, most notably, <em>in vitro</em> release testing (IVRT), <em>in vitro</em> permeation testing (IVPT), stratum corneum sampling via tape stripping (TS), and the vasoconstriction assay for corticosteroids. Based on the draft guideline version released in 2018, preliminary experience has been gathered in recent years regarding the implementation and practical applicability of some testing parameters proposed. However, this early engagement also exposed several ambiguities and limitations in the draft guidance, prompting expectations that the finalized version would address these deficiencies and offer more comprehensive direction on the use of these methods. The present paper is intended to summarize these known limitations and critically examine selected aspects of the guideline. Thereby, it seeks to provide an informed perspective on the scope, robustness, and regulatory utility of the final guideline, and to facilitate a dialogue on its practical implementation in regulatory and industrial settings.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114971"},"PeriodicalIF":4.3,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145818632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-20DOI: 10.1016/j.ejpb.2025.114970
Qiyao Zhai , Shuang Guo , Zhixiang Cui , Lu Qin , Jian Guan , Xin Zhang , Shirui Mao
The development of oral insulin delivery systems has advanced significantly, with polyelectrolyte nanocomplexes (PEC) showing promise due to their solvent-free synthesis. However, their efficacy is limited by poor mucus penetration and intestinal absorption. Inspired by the nature of mucin, chitosan (CS) modified with proline, threonine and serine to mimic the mucin’s PTS sequence were synthesized to enhance mucus permeability of the PEC. To further improve the mucus permeability and the trans-epithelial transport of the PEC, muco-penetrating nanocomplexes were fabricated by utilizing hyaluronic acid (HA), thus forming a surface with high-density positive and negative charges to mimic the surface charge properties of viruses. The nanocomplexes were self-assembled using modified CS and insulin, followed by HA coating. It was demonstrated that the nanocomplexes exhibited good physical stability, enhanced protection against enzymatic degradation, and increased penetration efficiency across the mucus layer and small intestine compared to unmodified counterparts. Furthermore, the in vivo hypoglycemic study further revealed a 2.16-fold increase in relative pharmacological availability for the nanocomplexes over the CS/Ins PEC Collectively, these findings reveal the potential of (PTS-CS/Ins)/HA, a dual-mimicking muco-penetrating nanocomplex based on the nature of mucin and virus, as a promising platform for oral insulin delivery.
{"title":"Exploration of a dual-mimetic mucus inert nanocomplex for enhanced oral insulin delivery","authors":"Qiyao Zhai , Shuang Guo , Zhixiang Cui , Lu Qin , Jian Guan , Xin Zhang , Shirui Mao","doi":"10.1016/j.ejpb.2025.114970","DOIUrl":"10.1016/j.ejpb.2025.114970","url":null,"abstract":"<div><div>The development of oral insulin delivery systems has advanced significantly, with polyelectrolyte nanocomplexes (PEC) showing promise due to their solvent-free synthesis. However, their efficacy is limited by poor mucus penetration and intestinal absorption. Inspired by the nature of mucin, chitosan (CS) modified with proline, threonine and serine to mimic the mucin’s PTS sequence were synthesized to enhance mucus permeability of the PEC. To further improve the mucus permeability and the <em>trans</em>-epithelial transport of the PEC, muco-penetrating nanocomplexes were fabricated by utilizing hyaluronic acid (HA), thus forming a surface with high-density positive and negative charges to mimic the surface charge properties of viruses. The nanocomplexes were self-assembled using modified CS and insulin, followed by HA coating. It was demonstrated that the nanocomplexes exhibited good physical stability, enhanced protection against enzymatic degradation, and increased penetration efficiency across the mucus layer and small intestine compared to unmodified counterparts. Furthermore, the <em>in vivo</em> hypoglycemic study further revealed a 2.16-fold increase in relative pharmacological availability for the nanocomplexes over the CS/Ins PEC Collectively, these findings reveal the potential of (PTS-CS/Ins)/HA, a dual-mimicking muco-penetrating nanocomplex based on the nature of mucin and virus, as a promising platform for oral insulin delivery.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114970"},"PeriodicalIF":4.3,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
5-fluorouracil (5-FU) is one of the most effective chemotherapeutic drugs for various solid tumors. However, its low water solubility and limited absorption rates in the stomach are crucial limitations that prevent it from being effectively applied in clinical practice. To address these issues, we first encapsulated 5-FU in β-cyclodextrin (5-FU–β-CD) to enhance its solubility, and the resulting 5-FU–β-CD was then loaded into a PLA film to prepare a novel gastro-retentive drug delivery system (GRDDS) based on shape-memory properties. The excipients, such as tributyl citrate (TBC), hydroxyethyl cellulose (HEC), citric acid (CA), and sodium bicarbonate (NaHCO3), were incorporated into the PLA matrix at an optimized ratio. This was done to enhance the performance of PLA as an ideal matrix material in GRDDS, including improvements in drug release, floating behavior, shape recovery, gastric retention, and in vivo anti-tumor activity. The results suggested that the solubility of the 5-FU–β-CD inclusion complex was significantly enhanced, which was 1.88-fold higher than that of pure 5-FU. The optimal shape-memory drug delivery formulation, 5-FU–β-CD–PLA/TBC (86/14), prepared in this study consists of PLA/TBC (86/14) incorporating 3 % HEC, 3 % NaHCO3, 1 % CA, and 3 % 5-FU. Its gastric retention time was notably prolonged to approximately 8 h following oral administration in mice, whereas the residual amount of 5-FU–β-CD at this time point was much lower than the initial loading. The oral bioavailability of the 5-FU–β-CD–PLA/TBC (86/14) was 269 % higher than that of pure 5-FU. Additionally, the mean tumor size and weight in the mouse model of gastric carcinoma administered with 5-FU–β-CD–PLA/TBC (86/14) were 215.3 mm3 and 241.4 mg respectively, significantly smaller than those in the 5-FU group. This indicates that the novel PLA-based drug delivery system has significantly enhanced anti-tumor effects. Its excellent therapeutic effects were further confirmed through HE, Ki67, and TUNEL staining. Taken together, 5-FU–β-CD–PLA/TBC (86/14) can be retained in the stomach to improve relative bioavailability. This system represents a promising carrier not only for 5-FU but also for other poorly soluble drugs that require prolonged retention in the stomach.
{"title":"Novel PLA-based shape-memory formulation: Design, preparation, and evaluation for gastro-retentive delivery of 5-fluorouracil to enhance oral bioavailability","authors":"Fengxue Liu , Xuefei Yu , Yanmei Wu , Ting Zhu , Ning Chen , Hao Chen , Wei Shen , Wei Zheng","doi":"10.1016/j.ejpb.2025.114968","DOIUrl":"10.1016/j.ejpb.2025.114968","url":null,"abstract":"<div><div>5-fluorouracil (5-FU) is one of the most effective chemotherapeutic drugs for various solid tumors. However, its low water solubility and limited absorption rates in the stomach are crucial limitations that prevent it from being effectively applied in clinical practice. To address these issues, we first encapsulated 5-FU in β-cyclodextrin (5-FU–β-CD) to enhance its solubility, and the resulting 5-FU–β-CD was then loaded into a PLA film to prepare a novel gastro-retentive drug delivery system (GRDDS) based on shape-memory properties. The excipients, such as tributyl citrate (TBC), hydroxyethyl cellulose (HEC), citric acid (CA), and sodium bicarbonate (NaHCO<sub>3</sub>), were incorporated into the PLA matrix at an optimized ratio. This was done to enhance the performance of PLA as an ideal matrix material in GRDDS, including improvements in drug release, floating behavior, shape recovery, gastric retention, and in vivo anti-tumor activity. The results suggested that the solubility of the 5-FU–β-CD inclusion complex was significantly enhanced, which was 1.88-fold higher than that of pure 5-FU. The optimal shape-memory drug delivery formulation, 5-FU–β-CD–PLA/TBC (86/14), prepared in this study consists of PLA/TBC (86/14) incorporating 3 % HEC, 3 % NaHCO<sub>3</sub>, 1 % CA, and 3 % 5-FU. Its gastric retention time was notably prolonged to approximately 8 h following oral administration in mice, whereas the residual amount of 5-FU–β-CD at this time point was much lower than the initial loading. The oral bioavailability of the 5-FU–β-CD–PLA/TBC (86/14) was 269 % higher than that of pure 5-FU. Additionally, the mean tumor size and weight in the mouse model of gastric carcinoma administered with 5-FU–β-CD–PLA/TBC (86/14) were 215.3 mm<sup>3</sup> and 241.4 mg respectively, significantly smaller than those in the 5-FU group. This indicates that the novel PLA-based drug delivery system has significantly enhanced anti-tumor effects. Its excellent therapeutic effects were further confirmed through HE, Ki67, and TUNEL staining. Taken together, 5-FU–β-CD–PLA/TBC (86/14) can be retained in the stomach to improve relative bioavailability. This system represents a promising carrier not only for 5-FU but also for other poorly soluble drugs that require prolonged retention in the stomach.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"220 ","pages":"Article 114968"},"PeriodicalIF":4.3,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.ejpb.2025.114967
Rongjian Hu , Xian Zhang , Weibin Shao , Na Li , Li Kang , Xin Wang
Tumor recurrence after surgery remains a major challenge. Herein, an orthoester (OE) compound was synthesized as a liquid pharmaceutical excipient. Next, an injectable suspension loaded with biomimetic nanoparticles and photothermal agents was constructed based on OE to inhibit tumor recurrence. The synthesized OE has the characteristics of simple structure, acid-sensitivity, clear degradation mechanism in vivo. More importantly, as a liquid excipient, OE can dissolve or disperse a variety of drugs, biomacromolecules or nanoparticles to form a stable suspension at extremely high concentrations. Thus, dasatinib (DAS) and sunitinib (SUN) were self-assembled to form nanoparticles, and cancer cell membrane vesicles were coated to obtain biomimetic nanoparticles (HCM@NPs). The self-assembly of DAS and SUN induces molecular aggregation, resulting in an aggregation-induced emission (AIE) effect, which facilitates the tracking of intracellular drug delivery. HCM@NPs and photothermal agent IR820 were co-dispersed in OE to obtain a synergistic therapeutic suspension (OE/IR/HCM@NPs). The suspension can be injected around the tumor or applied directly to the surgical bed to cover any suspicious areas. OE significantly improves the photothermal conversion efficiency of IR820 through its exceptionally low specific heat capacity (1.8 J/(g·℃)), which is markedly lower than that of water (4.2 J/(g·℃). In vitro and in vivo data demonstrated that the OE-based suspension directly inhibited tumor growth and prevented tumor recurrence. All mice receiving chemotherapy alone succumbed within 26 days due to tumor recurrence, whereas 66 % of those treated with the OE nano-suspension exhibited complete suppression of tumor recurrence over the observation period. This paper provides a new idea for the development of suspensions based on OE.
{"title":"A biomimetic nano-suspension based on orthoester designed for the inhibition of postoperative tumor recurrence","authors":"Rongjian Hu , Xian Zhang , Weibin Shao , Na Li , Li Kang , Xin Wang","doi":"10.1016/j.ejpb.2025.114967","DOIUrl":"10.1016/j.ejpb.2025.114967","url":null,"abstract":"<div><div>Tumor recurrence after surgery remains a major challenge. Herein, an orthoester (OE) compound was synthesized as a liquid pharmaceutical excipient. Next, an injectable suspension loaded with biomimetic nanoparticles and photothermal agents was constructed based on OE to inhibit tumor recurrence. The synthesized OE has the characteristics of simple structure, acid-sensitivity, clear degradation mechanism <em>in vivo</em>. More importantly, as a liquid excipient, OE can dissolve or disperse a variety of drugs, biomacromolecules or nanoparticles to form a stable suspension at extremely high concentrations. Thus, dasatinib (DAS) and sunitinib (SUN) were self-assembled to form nanoparticles, and cancer cell membrane vesicles were coated to obtain biomimetic nanoparticles (HCM@NPs). The self-assembly of DAS and SUN induces molecular aggregation, resulting in an aggregation-induced emission (AIE) effect, which facilitates the tracking of intracellular drug delivery. HCM@NPs and photothermal agent IR820 were co-dispersed in OE to obtain a synergistic therapeutic suspension (OE/IR/HCM@NPs). The suspension can be injected around the tumor or applied directly to the surgical bed to cover any suspicious areas. OE significantly improves the photothermal conversion efficiency of IR820 through its exceptionally low specific heat capacity (1.8 J/(g·℃)), which is markedly lower than that of water (4.2 J/(g·℃)<em>. In vitro</em> and <em>in vivo</em> data demonstrated that the OE-based suspension directly inhibited tumor growth and prevented tumor recurrence. All mice receiving chemotherapy alone succumbed within 26 days due to tumor recurrence, whereas 66 % of those treated with the OE nano-suspension exhibited complete suppression of tumor recurrence over the observation period. This paper provides a new idea for the development of suspensions based on OE.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"219 ","pages":"Article 114967"},"PeriodicalIF":4.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.ejpb.2025.114965
Anna Fedorko , Carolin Tetyczka , Jesús Alberto Afonso Urich
The oxidation stability of Tween® 80, a widely used surfactant in pharmaceutical formulations, was analyzed in-depth to predict its shelf life under pharmaceutical stability conditions. This study aimed to determine the influence of oxidative degradation on the stability of nanoemulsions (NEs) by assessing peroxide formation as a marker of oxidation. By correlating the amount of oxygen absorbed with the oxidation level, a novel mathematical approach was proposed to estimate real-time shelf-life predictions, specifically determining the time required to reach a peroxide value of 10 (mEq O2)·kg−1. Furthermore, nanoemulsions prepared with Tween® 80 at varying levels of oxidative degradation were analyzed. While no significant differences were observed in the overall properties (droplet size, polydispersity index) of these formulations compared to the control, a slight increase in zeta potential and partial degradation of the active pharmaceutical ingredient (API) were detected when oxidized Tween® 80 was used. These findings suggest a potential impact on system stability, emphasizing the need for further long-term investigations to fully understand the implications of oxidative degradation on pharmaceutical nanoemulsions.
{"title":"Understanding peroxide formation in Tween® 80 using RapidOxy®: Implications for pharmaceutical nanoemulsions","authors":"Anna Fedorko , Carolin Tetyczka , Jesús Alberto Afonso Urich","doi":"10.1016/j.ejpb.2025.114965","DOIUrl":"10.1016/j.ejpb.2025.114965","url":null,"abstract":"<div><div>The oxidation stability of Tween® 80, a widely used surfactant in pharmaceutical formulations, was analyzed in-depth to predict its shelf life under pharmaceutical stability conditions. This study aimed to determine the influence of oxidative degradation on the stability of nanoemulsions (NEs) by assessing peroxide formation as a marker of oxidation. By correlating the amount of oxygen absorbed with the oxidation level, a novel mathematical approach was proposed to estimate real-time shelf-life predictions, specifically determining the time required to reach a peroxide value of 10 (mEq O<sub>2</sub>)·kg<sup>−1</sup>. Furthermore, nanoemulsions prepared with Tween® 80 at varying levels of oxidative degradation were analyzed. While no significant differences were observed in the overall properties (droplet size, polydispersity index) of these formulations compared to the control, a slight increase in zeta potential and partial degradation of the active pharmaceutical ingredient (API) were detected when oxidized Tween® 80 was used. These findings suggest a potential impact on system stability, emphasizing the need for further long-term investigations to fully understand the implications of oxidative degradation on pharmaceutical nanoemulsions.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"219 ","pages":"Article 114965"},"PeriodicalIF":4.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145774036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lipid-based excipients (LBE) are a crucial class of functional excipients with significant potential for pharmaceutical formulation and product development. The wide variety of molecules in this class provides opportunities for designing novel dosage forms. However, the utilization of LBEs for 3D-printing applications is currently limited, thereby hindering the full potential of lipids and impeding the advancement of 3D-printing technologies. Notably, only a few publications report the 3D-printing of lipid-based formulations. This review provides a detailed discussion and analysis of these publications. It elucidates the revolutionary capabilities of 3D-printing and presents the potential of LBEs as functional pharmaceutical excipients, with a particular focus on 3D-printing applications. Additionally, the review provides an overview of the current challenges from material perspectives and suggests potential future research topics related to LBEs for 3D-printing of personalized medicine.
{"title":"3D-printing of lipid formulations: Going slow in a fast-paced field","authors":"Moaaz Abdelhamid , Dalip Kumar , Martin Spoerk , Sharareh Salar-Behzadi","doi":"10.1016/j.ejpb.2025.114964","DOIUrl":"10.1016/j.ejpb.2025.114964","url":null,"abstract":"<div><div>Lipid-based excipients (LBE) are a crucial class of functional excipients with significant potential for pharmaceutical formulation and product development. The wide variety of molecules in this class provides opportunities for designing novel dosage forms. However, the utilization of LBEs for 3D-printing applications is currently limited, thereby hindering the full potential of lipids and impeding the advancement of 3D-printing technologies. Notably, only a few publications report the 3D-printing of lipid-based formulations. This review provides a detailed discussion and analysis of these publications. It elucidates the revolutionary capabilities of 3D-printing and presents the potential of LBEs as functional pharmaceutical excipients, with a particular focus on 3D-printing applications. Additionally, the review provides an overview of the current challenges from material perspectives and suggests potential future research topics related to LBEs for 3D-printing of personalized medicine.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"219 ","pages":"Article 114964"},"PeriodicalIF":4.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15DOI: 10.1016/j.ejpb.2025.114966
Alexandra Hübl , Johannes Most , Christopher Hauß, Viktoria Planz, Maike Windbergs
Despite considerable efforts in antibiotic therapy, pulmonary infections caused by Pseudomonas aeruginosa remain a major challenge, particularly in diseases such as cystic fibrosis. Bacteriophage-antibiotic combinations have recently emerged as a potential alternative due to synergistic effects and the ability to overcome resistance. However, phage instability and sensitivity continue to hinder clinical translation.
In this study, we developed an inhalable spray-dried microparticle formulation co-encapsulating bacteriophages against P. aeruginosa and the β-lactam antibiotic aztreonam using mannitol, leucine, and trehalose as excipients. The particles exhibited favorable aerosol properties for deep lung delivery (geometric diameter: 1.39 ± 0.11 µm, mass median aerodynamic diameter: 2.42 ± 0.14 µm) and a burst release profile enabling immediate antimicrobial activity. Aztreonam was efficiently encapsulated (97.87 ± 0.91 %), while phage viability could be maintained through processing, remaining stable for 28 days at 4 and −20 °C. Therapeutic efficacy was confirmed by treatment of P. aeruginosa biofilms. A reduction in bacterial load by 99.90 % was achieved within 24 h. Microparticle biocompatibility was demonstrated in vitro using human lung epithelial cells.
The spray-dried phage-aztreonam microparticles enabled phage viability and stability in a formulation and highlight the feasibility of phage-antibiotic co-delivery through dry powder inhalation therapy for treating pulmonary P. aeruginosa infections.
{"title":"Development of spray-dried phage-aztreonam microparticles for inhalation therapy of Pseudomonas aeruginosa lung infections","authors":"Alexandra Hübl , Johannes Most , Christopher Hauß, Viktoria Planz, Maike Windbergs","doi":"10.1016/j.ejpb.2025.114966","DOIUrl":"10.1016/j.ejpb.2025.114966","url":null,"abstract":"<div><div>Despite considerable efforts in antibiotic therapy, pulmonary infections caused by <em>Pseudomonas aeruginosa</em> remain a major challenge, particularly in diseases such as cystic fibrosis. Bacteriophage-antibiotic combinations have recently emerged as a potential alternative due to synergistic effects and the ability to overcome resistance. However, phage instability and sensitivity continue to hinder clinical translation.</div><div>In this study, we developed an inhalable spray-dried microparticle formulation co-encapsulating bacteriophages against <em>P. aeruginosa</em> and the <em>β</em>-lactam antibiotic aztreonam using mannitol, leucine, and trehalose as excipients. The particles exhibited favorable aerosol properties for deep lung delivery (geometric diameter: 1.39 ± 0.11 µm, mass median aerodynamic diameter: 2.42 ± 0.14 µm) and a burst release profile enabling immediate antimicrobial activity. Aztreonam was efficiently encapsulated (97.87 ± 0.91 %), while phage viability could be maintained through processing, remaining stable for 28 days at 4 and −20 °C. Therapeutic efficacy was confirmed by treatment of <em>P. aeruginosa</em> biofilms. A reduction in bacterial load by 99.90 % was achieved within 24 h. Microparticle biocompatibility was demonstrated <em>in vitro</em> using human lung epithelial cells.</div><div>The spray-dried phage-aztreonam microparticles enabled phage viability and stability in a formulation and highlight the feasibility of phage-antibiotic co-delivery through dry powder inhalation therapy for treating pulmonary <em>P. aeruginosa</em> infections.</div></div>","PeriodicalId":12024,"journal":{"name":"European Journal of Pharmaceutics and Biopharmaceutics","volume":"219 ","pages":"Article 114966"},"PeriodicalIF":4.3,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145773998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号