Pub Date : 2025-11-09eCollection Date: 2025-12-01DOI: 10.1016/j.ijpx.2025.100433
Peter Roelants, Reza Ranjbar Choubeh, Nico Verbeeck, Rabindranath Andujar, Torsten Schultz-Fademrecht, Patrick Garidel, Viktor Gross
Polysorbate 20 (PS20) and polysorbate 80 (PS80) are essential surfactants used to stabilize biopharmaceutical products, yet their highly heterogeneous mixtures and susceptibility to oxidation and enzymatic hydrolysis complicate routine analysis. We developed a hierarchical generative model that reconstructs entire liquid chromatography-mass spectrometry (LC-MS) measurements to automatically interpret complex polysorbate datasets. By embedding domain knowledge of base structures, oxyethylene chain lengths, fatty acid esterification, and isotope patterns, the model resolves individual subspecies and provides molecular-level composition. Applied to PS20 and PS80, the approach distinguishes oxidative from hydrolytic degradation and yields pathway-specific fingerprints. Model outputs agree closely with manual integration while delivering greater depth and automation. This transforms polysorbate analysis from labor-intensive peak-by-peak workflows into an objective, comprehensive characterization tool suited for quality control, batch selection and degradation monitoring throughout development and manufacturing.
{"title":"Extraction of the polysorbate 20 and 80 fingerprint via generative modeling.","authors":"Peter Roelants, Reza Ranjbar Choubeh, Nico Verbeeck, Rabindranath Andujar, Torsten Schultz-Fademrecht, Patrick Garidel, Viktor Gross","doi":"10.1016/j.ijpx.2025.100433","DOIUrl":"10.1016/j.ijpx.2025.100433","url":null,"abstract":"<p><p>Polysorbate 20 (PS20) and polysorbate 80 (PS80) are essential surfactants used to stabilize biopharmaceutical products, yet their highly heterogeneous mixtures and susceptibility to oxidation and enzymatic hydrolysis complicate routine analysis. We developed a hierarchical generative model that reconstructs entire liquid chromatography-mass spectrometry (LC-MS) measurements to automatically interpret complex polysorbate datasets. By embedding domain knowledge of base structures, oxyethylene chain lengths, fatty acid esterification, and isotope patterns, the model resolves individual subspecies and provides molecular-level composition. Applied to PS20 and PS80, the approach distinguishes oxidative from hydrolytic degradation and yields pathway-specific fingerprints. Model outputs agree closely with manual integration while delivering greater depth and automation. This transforms polysorbate analysis from labor-intensive peak-by-peak workflows into an objective, comprehensive characterization tool suited for quality control, batch selection and degradation monitoring throughout development and manufacturing.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"100433"},"PeriodicalIF":6.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12681885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.ijpx.2025.100442
Toni Wildgrube, Stefan Senekowitsch, Robin Krüger, Fabian Winter, Michael Grimm, Werner Weitschies, Philipp Schick
Gastric emptying is a critical determinant of the pharmacokinetics of orally administered drugs. A key limitation in studies using caffeine as a marker for gastric emptying is the requirement for prior caffeine abstinence, which can complicate study design and participant recruitment. The present study was conducted with the objective of evaluating the potential use of the methylurates methylliberine and theacrine as novel salivary markers for the assessment of gastric emptying of non-caloric liquids, in comparison to the established marker caffeine. A Salivary Tracer Technique (STT) was employed in a crossover study that involved twelve healthy volunteers. The subjects participating in the study were under fasted state conditions according to the guidelines of the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) when they received ice capsules containing either caffeine, methylliberine, theacrine, or a combination of these three substances. Salivary samples were collected at predetermined intervals over 24 h in order to analyse their pharmacokinetic profiles. The results demonstrated a rapid absorption, with maximum salivary concentrations (cmax) reached within 30 min for all markers. It is noteworthy that methylliberine and theacrine exhibited strong correlations with caffeine in their absorption profiles, with Pearson correlation coefficients of r = 0.9973 and r = 0.9865, respectively, during the initial 40 min post-administration. Furthermore, the elimination half-lives (t1/2) of methylliberine and theacrine were found to differ significantly, with methylliberine exhibiting a rapid elimination profile (t1/2 = 1.15 ± 0.12 h) in comparison to theacrine (t1/2 = 21.00 ± 7.55 h). These results support methylliberine and theacrine as promising non-invasive markers of gastric emptying, offering viable alternatives to caffeine that may eliminate the need for abstinence and may allow for more efficient multi-tracer pharmacokinetic studies.
{"title":"A comparison of theacrine and methylliberine with caffeine as salivary markers for determining gastric emptying","authors":"Toni Wildgrube, Stefan Senekowitsch, Robin Krüger, Fabian Winter, Michael Grimm, Werner Weitschies, Philipp Schick","doi":"10.1016/j.ijpx.2025.100442","DOIUrl":"10.1016/j.ijpx.2025.100442","url":null,"abstract":"<div><div>Gastric emptying is a critical determinant of the pharmacokinetics of orally administered drugs. A key limitation in studies using caffeine as a marker for gastric emptying is the requirement for prior caffeine abstinence, which can complicate study design and participant recruitment. The present study was conducted with the objective of evaluating the potential use of the methylurates methylliberine and theacrine as novel salivary markers for the assessment of gastric emptying of non-caloric liquids, in comparison to the established marker caffeine. A Salivary Tracer Technique (STT) was employed in a crossover study that involved twelve healthy volunteers. The subjects participating in the study were under fasted state conditions according to the guidelines of the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) when they received ice capsules containing either caffeine, methylliberine, theacrine, or a combination of these three substances. Salivary samples were collected at predetermined intervals over 24 h in order to analyse their pharmacokinetic profiles. The results demonstrated a rapid absorption, with maximum salivary concentrations (c<sub>max</sub>) reached within 30 min for all markers. It is noteworthy that methylliberine and theacrine exhibited strong correlations with caffeine in their absorption profiles, with Pearson correlation coefficients of <em>r</em> = 0.9973 and <em>r</em> = 0.9865, respectively, during the initial 40 min post-administration. Furthermore, the elimination half-lives (t<sub>1/2</sub>) of methylliberine and theacrine were found to differ significantly, with methylliberine exhibiting a rapid elimination profile (t<sub>1/2</sub> = 1.15 ± 0.12 h) in comparison to theacrine (t<sub>1/2</sub> = 21.00 ± 7.55 h). These results support methylliberine and theacrine as promising non-invasive markers of gastric emptying, offering viable alternatives to caffeine that may eliminate the need for abstinence and may allow for more efficient multi-tracer pharmacokinetic studies.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100442"},"PeriodicalIF":6.4,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516729","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 : 2025-11-07DOI: 10.1016/j.ijpx.2025.100441
Ivana Ruseska , Amina Tucak-Smajić , Ivan Vidaković , Karin Kornmüller , Edina Vranić , Andreas Zimmer
microRNA-27a is a promising candidate for miRNA mimic therapy to combat obesity, but its clinical application is hindered by enzymatic degradation and low membrane permeability. To address these challenges, we developed cationic nanostructured lipid carriers (cNLCs) via high-pressure homogenization as non-viral carriers for miRNA-27a. However, the formation of a protein corona in biologically-relevant media altered the particle size and surface charge, significantly reducing cellular uptake. To mitigate this issue, we hypothesized that coating miRNA/cNLC complexes with human serum albumin (HSA) will prevent protein corona formation and enhance cellular uptake. The HSA-coated miRNA/cNLC complexes, termed albuplexes, were characterized for particle size, zeta potential, morphology, and stability in various media. The integrity of the HSA coat was assessed using circular dichroism and UV/Vis spectroscopy. We also evaluated the biocompatibility and cellular uptake of albuplexes in 3T3-L1 cells. The biological effects of miRNA-27a on adipocyte development were analyzed through light microscopy and absorbance measurements of Oil-red-O dye in lipid droplets. Results indicated that albuplexes possess favourable physicochemical properties and enhanced stability in serum. Notably, albuplexes were rapidly taken up by 3T3-L cells via endocytosis, although 20 % HSA in the culture medium completely inhibited uptake. Furthermore, albuplexes exhibited an anti-adipogenic effect by reducing the lipid droplet accumulation, suggesting their potential as a therapeutic strategy for miRNA replacement in obesity treatment.
{"title":"Optimizing microRNA delivery via albumin-decorated nanostructured lipid carriers","authors":"Ivana Ruseska , Amina Tucak-Smajić , Ivan Vidaković , Karin Kornmüller , Edina Vranić , Andreas Zimmer","doi":"10.1016/j.ijpx.2025.100441","DOIUrl":"10.1016/j.ijpx.2025.100441","url":null,"abstract":"<div><div>microRNA-27a is a promising candidate for miRNA mimic therapy to combat obesity, but its clinical application is hindered by enzymatic degradation and low membrane permeability. To address these challenges, we developed cationic nanostructured lipid carriers (cNLCs) via high-pressure homogenization as non-viral carriers for miRNA-27a. However, the formation of a protein corona in biologically-relevant media altered the particle size and surface charge, significantly reducing cellular uptake. To mitigate this issue, we hypothesized that coating miRNA/cNLC complexes with human serum albumin (HSA) will prevent protein corona formation and enhance cellular uptake. The HSA-coated miRNA/cNLC complexes, termed albuplexes, were characterized for particle size, zeta potential, morphology, and stability in various media. The integrity of the HSA coat was assessed using circular dichroism and UV/Vis spectroscopy. We also evaluated the biocompatibility and cellular uptake of albuplexes in 3T3-L1 cells. The biological effects of miRNA-27a on adipocyte development were analyzed through light microscopy and absorbance measurements of Oil-red-O dye in lipid droplets. Results indicated that albuplexes possess favourable physicochemical properties and enhanced stability in serum. Notably, albuplexes were rapidly taken up by 3T3-L cells via endocytosis, although 20 % HSA in the culture medium completely inhibited uptake. Furthermore, albuplexes exhibited an anti-adipogenic effect by reducing the lipid droplet accumulation, suggesting their potential as a therapeutic strategy for miRNA replacement in obesity treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100441"},"PeriodicalIF":6.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516616","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 : 2025-11-07DOI: 10.1016/j.ijpx.2025.100440
J. Siepmann, F. Siepmann
Poly(lactic-co-glycolic acid) (PLGA)-based microparticles and implants are of continuously increasing importance as parenteral controlled drug delivery systems. However, the underlying drug release mechanisms are often not understood, rendering product optimization difficult: The effects of formulation and processing parameters on drug release can be surprising. Also, upscaling and troubleshooting during production at industrial scale can be highly cumbersome. This can be attributed to the complexity of the physicochemical processes, which can be involved in the control of drug release. Generally, tri-phasic drug release patterns are observed: An initial burst release is followed by a zero order release phase and a final, again, rapid release phase. The relative importance of the different phases can strongly depend on the: (i) composition (e.g., type & amount of drug and polymer), geometry and dimensions of the system, (ii) manufacturing procedure, and (iii) conditions in the surrounding environment (e.g., bulk fluid versus human tissue). Water penetration into the system, drug dissolution, limited solubility effects, drug diffusion through an “intact polymeric matrix” (polymer phase) and/or through water filled pores, pore closure due to local PLGA swelling, osmotic effects, polymer degradation, local drops in micro-pH, autocatalytic effects, substantial swelling of the entire system as well as other phenomena can be of importance. This article aims at giving an overview on the current knowledge in this field. Please note that it is hypotheses-driven, thus, general conclusions should be seen with caution. Also, each drug delivery system should be considered on a case-by-case basis. This article also aims at raising awareness on two aspects, which are often neglected: (i) Substantial system swelling is likely the root cause for the onset of the third drug release phase in many systems. (ii) In the case of microparticles, only looking at drug release from ensembles (hundreds of thousands/millions) of particles can be misleading.
{"title":"Release mechanisms of PLGA-based drug delivery systems: A review","authors":"J. Siepmann, F. Siepmann","doi":"10.1016/j.ijpx.2025.100440","DOIUrl":"10.1016/j.ijpx.2025.100440","url":null,"abstract":"<div><div>Poly(lactic-<em>co</em>-glycolic acid) (PLGA)-based microparticles and implants are of continuously increasing importance as parenteral controlled drug delivery systems. However, the underlying drug release mechanisms are often not understood, rendering product optimization difficult: The effects of formulation and processing parameters on drug release can be surprising. Also, upscaling and troubleshooting during production at industrial scale can be highly cumbersome. This can be attributed to the complexity of the physicochemical processes, which can be involved in the control of drug release. Generally, tri-phasic drug release patterns are observed: An initial burst release is followed by a zero order release phase and a final, again, rapid release phase. The relative importance of the different phases can strongly depend on the: (i) composition (e.g., type & amount of drug and polymer), geometry and dimensions of the system, (ii) manufacturing procedure, and (iii) conditions in the surrounding environment (e.g., bulk fluid versus human tissue). Water penetration into the system, drug dissolution, limited solubility effects, drug diffusion through an “intact polymeric matrix” (polymer phase) and/or through water filled pores, pore closure due to local PLGA swelling, osmotic effects, polymer degradation, local drops in micro-pH, autocatalytic effects, substantial swelling of the entire system as well as other phenomena can be of importance. This article aims at giving an overview on the current knowledge in this field. Please note that it is <em>hypotheses-driven</em>, thus, general conclusions should be seen with caution. Also, each drug delivery system should be considered on a <em>case-by-case basis</em>. This article also aims at raising awareness on two aspects, which are often neglected: (i) Substantial system swelling is likely the root cause for the onset of the <em>third</em> drug release phase in many systems. (ii) In the case of <em>microparticles</em>, only looking at drug release from <em>ensembles</em> (hundreds of thousands/millions) of particles can be misleading.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100440"},"PeriodicalIF":6.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516737","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 : 2025-11-06DOI: 10.1016/j.ijpx.2025.100439
Alžběta Turnovská, Tomáš Etrych
Photodynamic therapy (PDT) is widely studied and complex method useful as a minimally invasive cancer treatment strategy, relying on photosensitizers (PSs), light, and oxygen to induce cytotoxicity. Indeed, the controlled delivery of conventional PSs is the key factor in achieving effective treatment outcome. Among many drug delivery systems, the polymeric micelles represent a promising platform to address the solubility, stability, and delivery challenges associated with PSs. The design of micelles, constructed from hydrophilic and hydrophobic polymeric blocks in diverse structures, enables precise tailoring of carrier properties to optimize PS delivery. This paper focuses on the potential applications and limitations of polymer micelles for the controlled delivery of PSs in the field anticancer therapy. Various methods of synthesis, incorporation of PSs as well as their release and activation are described in detail. The effect of micellar system employment on circulation time, off-target effects, and both passive and active targeting are thoroughly depicted. Despite the clinical promise, the limitations of PDT including shallow tissue penetration and restricted applicability to superficial or endoscope-accessible tumors are discussed, as well as the future prospects consisting in red-shifted or two-photon absorption systems.
{"title":"Polymeric micelles in advanced photodynamic therapy: Design, delivery and translational prospects","authors":"Alžběta Turnovská, Tomáš Etrych","doi":"10.1016/j.ijpx.2025.100439","DOIUrl":"10.1016/j.ijpx.2025.100439","url":null,"abstract":"<div><div>Photodynamic therapy (PDT) is widely studied and complex method useful as a minimally invasive cancer treatment strategy, relying on photosensitizers (PSs), light, and oxygen to induce cytotoxicity. Indeed, the controlled delivery of conventional PSs is the key factor in achieving effective treatment outcome. Among many drug delivery systems, the polymeric micelles represent a promising platform to address the solubility, stability, and delivery challenges associated with PSs. The design of micelles, constructed from hydrophilic and hydrophobic polymeric blocks in diverse structures, enables precise tailoring of carrier properties to optimize PS delivery. This paper focuses on the potential applications and limitations of polymer micelles for the controlled delivery of PSs in the field anticancer therapy. Various methods of synthesis, incorporation of PSs as well as their release and activation are described in detail. The effect of micellar system employment on circulation time, off-target effects, and both passive and active targeting are thoroughly depicted. Despite the clinical promise, the limitations of PDT including shallow tissue penetration and restricted applicability to superficial or endoscope-accessible tumors are discussed, as well as the future prospects consisting in red-shifted or two-photon absorption systems.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100439"},"PeriodicalIF":6.4,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516733","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 : 2025-11-05DOI: 10.1016/j.ijpx.2025.100436
Meiru Liu , Yinru Jiang , Penghui Yuan , Shuang Li , Baoxi Zhang , Xia Zhou , Bin Su , Yifei Xie , Dezhi Yang , Linglei Kong , Li Zhang , Yang Lv , Guanhua Du
Emodin (EMO) shows therapeutic promise for ulcerative colitis (UC), yet its clinical utility is hampered by low bioavailability. To rationally overcome this limitation, this study employed cocrystal engineering, strategically selecting tetramethylpyrazine (TMP)—a natural compound from traditional Chinese medicine—as the cocrystal coformer (CCF). The selection of TMP was guided by a systematic CCF screening strategy, incorporating extensive literature analysis of natural compound CCF candidates, computational chemistry methods to predict favorable hydrogen-bonding interactions and interaction sites with EMO, and machine learning assessment of cocrystallization propensity. Utilizing this rational design approach, we successfully synthesized and characterized a novel EMO-TMP cocrystal through comprehensive solid-state characterization techniques. The resulting cocrystal significantly enhanced the aqueous solubility of EMO while preserving its intrinsic bioactivity. Pharmacokinetic studies confirmed that the cocrystal formulation markedly improved the oral bioavailability of EMO. In a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model, the EMO-TMP cocrystal demonstrated superior efficacy compared to EMO alone, effectively alleviating colitis symptoms and associated pathological markers. This enhanced in vivo efficacy is attributed to the significantly improved systemic exposure achieved through the rationally designed cocrystal. Our findings establish the EMO-TMP cocrystal as a highly promising strategy to surmount the physicochemical barriers of EMO, unlocking its full clinical potential for UC treatment. Critically, this work not only validates TMP as an efficient and safe CCF specifically suited for active pharmaceutical ingredients (APIs) rich in hydrogen-bond donors, but also exemplifies the value of leveraging formulation principles and compatible components inherent in traditional Chinese medicine through advanced crystal engineering approaches.
{"title":"Crystal engineering optimizes emodin-tetramethylpyrazine combination: From cocrystal design to in vivo anti-colitis efficacy assessment","authors":"Meiru Liu , Yinru Jiang , Penghui Yuan , Shuang Li , Baoxi Zhang , Xia Zhou , Bin Su , Yifei Xie , Dezhi Yang , Linglei Kong , Li Zhang , Yang Lv , Guanhua Du","doi":"10.1016/j.ijpx.2025.100436","DOIUrl":"10.1016/j.ijpx.2025.100436","url":null,"abstract":"<div><div>Emodin (EMO) shows therapeutic promise for ulcerative colitis (UC), yet its clinical utility is hampered by low bioavailability. To rationally overcome this limitation, this study employed cocrystal engineering, strategically selecting tetramethylpyrazine (TMP)—a natural compound from traditional Chinese medicine—as the cocrystal coformer (CCF). The selection of TMP was guided by a systematic CCF screening strategy, incorporating extensive literature analysis of natural compound CCF candidates, computational chemistry methods to predict favorable hydrogen-bonding interactions and interaction sites with EMO, and machine learning assessment of cocrystallization propensity. Utilizing this rational design approach, we successfully synthesized and characterized a novel EMO-TMP cocrystal through comprehensive solid-state characterization techniques. The resulting cocrystal significantly enhanced the aqueous solubility of EMO while preserving its intrinsic bioactivity. Pharmacokinetic studies confirmed that the cocrystal formulation markedly improved the oral bioavailability of EMO. In a dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) model, the EMO-TMP cocrystal demonstrated superior efficacy compared to EMO alone, effectively alleviating colitis symptoms and associated pathological markers. This enhanced <em>in vivo</em> efficacy is attributed to the significantly improved systemic exposure achieved through the rationally designed cocrystal. Our findings establish the EMO-TMP cocrystal as a highly promising strategy to surmount the physicochemical barriers of EMO, unlocking its full clinical potential for UC treatment. Critically, this work not only validates TMP as an efficient and safe CCF specifically suited for active pharmaceutical ingredients (APIs) rich in hydrogen-bond donors, but also exemplifies the value of leveraging formulation principles and compatible components inherent in traditional Chinese medicine through advanced crystal engineering approaches.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100436"},"PeriodicalIF":6.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145516742","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 : 2025-11-01DOI: 10.1016/j.ijpx.2025.100434
Sahar Marefat , Ali Shayanfar , Farnaz Monajjemzadeh
The evaluation of color in pharmaceutical materials and products serves as an essential method for assessing physical appearance, stability, and overall quality control. Any recognizable color change in pharmaceuticals may lead to failure in meeting quality objectives. Traditional visual examinations, while commonly used, are subjective and prone to inconsistency, making them inadequate for precise assessment. As a result, advanced instrumental techniques have gained prominence, with CIE (Commission Internationale de l'Eclairage) Lab color space being widely recognized for its accuracy and applicability. Developed by the International Commission on Illumination, the CIELab system characterizes color using three components: L (lightness), a⁎ (red-green axis), and b⁎ (yellow-blue axis), providing a quantitative, standardized approach for color measurement. This method has been extensively utilized in pharmaceutical research and industry for diverse applications, such as quality control, stability studies, and batch-to-batch consistency evaluations. The present review aims to discuss studies that have employed this method in pharmaceutical color assessment, and related quality control issues.
{"title":"Developments in image-based colorimetric analysis methods and applications of CIElab color space in pharmaceutical sciences: A narrative review","authors":"Sahar Marefat , Ali Shayanfar , Farnaz Monajjemzadeh","doi":"10.1016/j.ijpx.2025.100434","DOIUrl":"10.1016/j.ijpx.2025.100434","url":null,"abstract":"<div><div>The evaluation of color in pharmaceutical materials and products serves as an essential method for assessing physical appearance, stability, and overall quality control. Any recognizable color change in pharmaceuticals may lead to failure in meeting quality objectives. Traditional visual examinations, while commonly used, are subjective and prone to inconsistency, making them inadequate for precise assessment. As a result, advanced instrumental techniques have gained prominence, with CIE (Commission Internationale de l'Eclairage) Lab color space being widely recognized for its accuracy and applicability. Developed by the International Commission on Illumination, the CIELab system characterizes color using three components: L (lightness), a<sup>⁎</sup> (red-green axis), and b<sup>⁎</sup> (yellow-blue axis), providing a quantitative, standardized approach for color measurement. This method has been extensively utilized in pharmaceutical research and industry for diverse applications, such as quality control, stability studies, and batch-to-batch consistency evaluations. The present review aims to discuss studies that have employed this method in pharmaceutical color assessment, and related quality control issues.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100434"},"PeriodicalIF":6.4,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462890","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 : 2025-10-31DOI: 10.1016/j.ijpx.2025.100430
Sadek Ahmed , Osama Saher , Rana M. ElBishbishy , Mennatullah M. Ibrahim
Drug-induced liver injury (DILI) represents a critical clinical problem that often necessitates lowering the therapeutic dose or even complete drug withdrawal, ultimately resulting in treatment failure. Curcumin (Cur), a natural polyphenolic compound, demonstrates strong hepatoprotective and antioxidant activity; however, its poor solubility and limited bioavailability hinder its therapeutic use. To overcome these limitations, the present study aimed to develop and optimize curcumin-loaded hyaluronic acid-modified edge-activated spanlastics (Cur-HES) as an efficient delivery system for enhancing the hepatoprotective efficacy of curcumin against carbon tetrachloride (CCl₄)-induced liver damage. Cur-HES were prepared using the ethanol injection method and systematically optimized via a 23 full factorial design, where the independent variables included hyaluronic acid-to-surfactant ratio (X1), edge activator-to-drug ratio (X2), and Span 80 % contribution (X3). Formulations were assessed for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimized formulation achieved a desirability value of 0.982, with EE% of 88.4 %, PS of 105.2 nm, PDI of 0.19, and ZP of −20.9 mV. Transmission electron microscopy revealed spherical vesicles. In-vitro release exhibited biphasic Higuchi diffusion kinetics, while stability testing confirmed preservation of physicochemical properties for three months. In-vivo evaluation demonstrated that Cur-HES provided significantly greater hepatoprotection than free Cur in the CCl₄-induced hepatotoxicity model, as evidenced by marked reductions in serum ALT and AST levels. Histopathological examination supported these findings, showing preserved liver architecture in treated groups. Overall, Cur-HES represents a promising nanocarrier platform to boost the hepatoprotective activity of Cur, offering a safe and effective therapeutic strategy against DILI.
{"title":"Revolutionary hyaluronic acid-modified edge-activated spanlastics as a novel approach to boost Hepatoprotective activity of Curcumin: Optimization, biochemical analysis and in-vivo assessment","authors":"Sadek Ahmed , Osama Saher , Rana M. ElBishbishy , Mennatullah M. Ibrahim","doi":"10.1016/j.ijpx.2025.100430","DOIUrl":"10.1016/j.ijpx.2025.100430","url":null,"abstract":"<div><div>Drug-induced liver injury (DILI) represents a critical clinical problem that often necessitates lowering the therapeutic dose or even complete drug withdrawal, ultimately resulting in treatment failure. Curcumin (Cur), a natural polyphenolic compound, demonstrates strong hepatoprotective and antioxidant activity; however, its poor solubility and limited bioavailability hinder its therapeutic use. To overcome these limitations, the present study aimed to develop and optimize curcumin-loaded hyaluronic acid-modified edge-activated spanlastics (Cur-HES) as an efficient delivery system for enhancing the hepatoprotective efficacy of curcumin against carbon tetrachloride (CCl₄)-induced liver damage. Cur-HES were prepared using the ethanol injection method and systematically optimized <em>via</em> a 23 full factorial design, where the independent variables included hyaluronic acid-to-surfactant ratio (X1), edge activator-to-drug ratio (X2), and Span 80 % contribution (X3). Formulations were assessed for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). The optimized formulation achieved a desirability value of 0.982, with EE% of 88.4 %, PS of 105.2 nm, PDI of 0.19, and ZP of −20.9 mV. Transmission electron microscopy revealed spherical vesicles. <em>In-vitro</em> release exhibited biphasic Higuchi diffusion kinetics, while stability testing confirmed preservation of physicochemical properties for three months. <em>In-vivo</em> evaluation demonstrated that Cur-HES provided significantly greater hepatoprotection than free Cur in the CCl₄-induced hepatotoxicity model, as evidenced by marked reductions in serum ALT and AST levels. Histopathological examination supported these findings, showing preserved liver architecture in treated groups. Overall, Cur-HES represents a promising nanocarrier platform to boost the hepatoprotective activity of Cur, offering a safe and effective therapeutic strategy against DILI.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100430"},"PeriodicalIF":6.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415928","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 : 2025-10-31DOI: 10.1016/j.ijpx.2025.100437
Qinghua Lan , Miao Wang , Yanyan Zhu , Xiayan Zhang , Ruolei Ye , Zhengbo Wu , HaiCi Lan , Songmei Luo , Yanyan Xu
Gastric cancer is a major cause of cancer-related mortality on a global scale. Although 5-fluorouracil (5-FU) is a cornerstone chemotherapeutic for digestive tract malignancies, its efficacy is limited by dose-dependent toxicity and acquired resistance. Quercetin (QUC), a natural flavonoid, can sensitize tumor cells to 5-FU by modulating cell cycle-regulatory proteins. However, its limited water solubility and low bioavailability present significant limitations on its potential therapeutic application. In this study, we developed bioinspired pH-sensitive liposomes (NK-Lip@Q) functionalized for active targeting and acid-triggered drug release to enhance QUC delivery and synergistic anticancer activity with 5-FU. NK-Lip@Q exhibited a mean particle size of 206.36 ± 1.81 nm, an encapsulation efficiency of 60.69 ± 1.32 %, and a pH-dependent release profile with 72.75 ± 0.69 % cumulative release at pH 5.4. Cellular studies demonstrated efficient uptake by N87 cells, marked apoptosis induction (apoptosis ratio: 69.60 ± 8.71 %), and enhanced cytotoxicity in combination with 5-FU (Chou-Talalay combination index, CI = 0.68). In vivo, NK-Lip@Q could precisely accumulate in the target area, when co-administered with 5-FU, achieved significant tumor inhibition (tumor inhibition rate: 92.26 %) without obvious systemic toxicity. QUC complemented the anticancer action of 5-FU by regulating cell cycle-related genes, promoting apoptosis, and suppressing proliferation. In conclusion, this study demonstrates that NK-Lip@Q as a promising nanocarrier system that enhances the therapeutic performance of 5-FU by improving its synergistic antitumor efficacy in gastric cancer.
{"title":"Bioinspired pH-sensitive liposomes for quercetin delivery to synergize with 5- FU in gastric cancer therapy","authors":"Qinghua Lan , Miao Wang , Yanyan Zhu , Xiayan Zhang , Ruolei Ye , Zhengbo Wu , HaiCi Lan , Songmei Luo , Yanyan Xu","doi":"10.1016/j.ijpx.2025.100437","DOIUrl":"10.1016/j.ijpx.2025.100437","url":null,"abstract":"<div><div>Gastric cancer is a major cause of cancer-related mortality on a global scale. Although 5-fluorouracil (5-FU) is a cornerstone chemotherapeutic for digestive tract malignancies, its efficacy is limited by dose-dependent toxicity and acquired resistance. Quercetin (QUC), a natural flavonoid, can sensitize tumor cells to 5-FU by modulating cell cycle-regulatory proteins. However, its limited water solubility and low bioavailability present significant limitations on its potential therapeutic application. In this study, we developed bioinspired pH-sensitive liposomes (NK-Lip@Q) functionalized for active targeting and acid-triggered drug release to enhance QUC delivery and synergistic anticancer activity with 5-FU. NK-Lip@Q exhibited a mean particle size of 206.36 ± 1.81 nm, an encapsulation efficiency of 60.69 ± 1.32 %, and a pH-dependent release profile with 72.75 ± 0.69 % cumulative release at pH 5.4. Cellular studies demonstrated efficient uptake by N87 cells, marked apoptosis induction (apoptosis ratio: 69.60 ± 8.71 %), and enhanced cytotoxicity in combination with 5-FU (Chou-Talalay combination index, CI = 0.68). In vivo, NK-Lip@Q could precisely accumulate in the target area, when co-administered with 5-FU, achieved significant tumor inhibition (tumor inhibition rate: 92.26 %) without obvious systemic toxicity. QUC complemented the anticancer action of 5-FU by regulating cell cycle-related genes, promoting apoptosis, and suppressing proliferation. In conclusion, this study demonstrates that NK-Lip@Q as a promising nanocarrier system that enhances the therapeutic performance of 5-FU by improving its synergistic antitumor efficacy in gastric cancer.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100437"},"PeriodicalIF":6.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462891","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}
The current study aimed to develop pH-responsive hydrogel beads based on sodium alginate (SA) and acrylic acid (Aa), crosslinked in the presence of calcium chloride, for the controlled delivery of ketorolac tromethamine. The hydrogel beads were fabricated using the ionic gelation technique and subsequently characterized for their structural properties, surface morphology, and thermal stability. Additional investigations, including sol-gel analysis, drug loading efficiency, and drug quantification, were conducted to evaluate the physicochemical attributes of the prepared beads. Furthermore, Monte Carlo simulations using the adsorption locator module in Materials Studio were conducted to investigate the adsorption behavior of ketorolac on the SA/Aa hydrogel beads. The negative adsorption energy obtained from the simulations suggested that the interaction between the drug and polymer was both spontaneous and exothermic, indicating a thermodynamically favorable binding mechanism. The pH responsiveness of the beads was evaluated through swelling and drug release studies under different pH conditions (pH 1.2 and 7.4). The results indicated markedly significant swelling and drug release at pH 7.4 as compared to 1.2, thereby confirming the pH-responsive behavior of the formulated beads. The toxicity of the hydrogel beads was evaluated using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM), which revealed no signs of irritation or toxicity. An in vivo pharmacokinetic study in rabbits further demonstrated that the drug-loaded hydrogel beads achieved higher plasma concentrations of ketorolac tromethamine compared to the drug solution, supporting their potential for improved bioavailability. Hence, the developed SA/Aa-based hydrogel beads exhibited favorable physicochemical, biocompatibility, and pharmacokinetic profiles, making them promising candidates for controlled drug delivery systems.
{"title":"Synthesis of pH-sensitive hydrogel beads for controlled delivery of ketorolac tromethamine: computational evaluation and in vivo pharmacokinetic study","authors":"Hamid Ullah , I-Hui Chiu , Rahime Eshaghi Malekshah , Muhammad Suhail , Pao-Chu Wu","doi":"10.1016/j.ijpx.2025.100435","DOIUrl":"10.1016/j.ijpx.2025.100435","url":null,"abstract":"<div><div>The current study aimed to develop pH-responsive hydrogel beads based on sodium alginate (SA) and acrylic acid (Aa), crosslinked in the presence of calcium chloride, for the controlled delivery of ketorolac tromethamine. The hydrogel beads were fabricated using the ionic gelation technique and subsequently characterized for their structural properties, surface morphology, and thermal stability. Additional investigations, including sol-gel analysis, drug loading efficiency, and drug quantification, were conducted to evaluate the physicochemical attributes of the prepared beads. Furthermore, Monte Carlo simulations using the adsorption locator module in Materials Studio were conducted to investigate the adsorption behavior of ketorolac on the SA/Aa hydrogel beads. The negative adsorption energy obtained from the simulations suggested that the interaction between the drug and polymer was both spontaneous and exothermic, indicating a thermodynamically favorable binding mechanism. The pH responsiveness of the beads was evaluated through swelling and drug release studies under different pH conditions (pH 1.2 and 7.4). The results indicated markedly significant swelling and drug release at pH 7.4 as compared to 1.2, thereby confirming the pH-responsive behavior of the formulated beads. The toxicity of the hydrogel beads was evaluated using the Hen's Egg Test on Chorioallantoic Membrane (HET-CAM), which revealed no signs of irritation or toxicity. An in vivo pharmacokinetic study in rabbits further demonstrated that the drug-loaded hydrogel beads achieved higher plasma concentrations of ketorolac tromethamine compared to the drug solution, supporting their potential for improved bioavailability. Hence, the developed SA/Aa-based hydrogel beads exhibited favorable physicochemical, biocompatibility, and pharmacokinetic profiles, making them promising candidates for controlled drug delivery systems.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"10 ","pages":"Article 100435"},"PeriodicalIF":6.4,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462896","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}
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