Journal of Drug Delivery Science and Technology最新文献

{"title":"Evaluation of lemon-derived extracellular nanovesicles as a nanocarrier for Clemastine: insights from intracellular calcium dynamics in an oligodendrocyte cell model","authors":"Mattia Danilo Langellotto ,&nbsp;Giovanna Rassu ,&nbsp;Maik Hintze ,&nbsp;Luis Miguel Lozano ,&nbsp;María del Rosario Aberturas ,&nbsp;Paolo Giunchedi ,&nbsp;Carla Serri ,&nbsp;Jesús Molpeceres ,&nbsp;Stefanie Kuerten ,&nbsp;Elisabetta Gavini","doi":"10.1016/j.jddst.2025.107963","DOIUrl":"10.1016/j.jddst.2025.107963","url":null,"abstract":"<div><div>Plant-derived extracellular nanovesicles are emerging as a natural drug delivery system, offering advantages like safety, scalability, stability, biocompatibility, and low immunogenicity. The purpose of this work is to introduce an innovative, environmentally friendly, and straightforward technique for the extraction of extracellular nanovesicles from organically grown lemons (LENVs) and explore their potential application as delivery systems of Clemastine (CLM), a promising remyelination agent. LENVs were isolated and characterised for size, stability over time and total protein content. CLM was loaded into LENVs, and the loading efficiency was quantified. Transmission Electron Microscopy (TEM) was used to confirm the morphological integrity of the vesicles before and after drug loading. Finally, the biological activity was evaluated in vitro on an oligodendrocyte progenitor cell model (MO3.13 cells) by analysing the modulation of intracellular calcium. LENVs were extracted using a novel self-separating two-phase method, yielding a fraction enriched with vesicles with an average size of 128 ± 8.6 nm, which showed stability over 28 days, low protein content, and 78 % loading efficiency. TEM analysis confirmed that LENVs maintained integrity after CLM loading. CLM-LENVs achieved a more pronounced and sustained reduction of intracellular calcium in MO3.13 cells compared to treatment with CLM alone, suggesting enhanced delivery efficiency. This modulation of intracellular calcium is important, as this mechanism plays a pivotal role in promoting the differentiation of oligodendrocytes into myelin-producing cells. This research, therefore, highlights the potential of LENVs as a novel, sustainable drug delivery platform for agents targeting key cellular processes relevant to neurodegenerative diseases such as multiple sclerosis.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107963"},"PeriodicalIF":4.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881102","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating controlled vibration with PVDF nanofiber dressings: Mechanistic insights into electromechanical wound healing","authors":"George Bebawy ,&nbsp;Asmaa Hegazy ,&nbsp;Ahmed H. Hassanin ,&nbsp;Nader Shehata ,&nbsp;Alyaa Ramadan ,&nbsp;Hebatallah S. Barakat","doi":"10.1016/j.jddst.2025.107964","DOIUrl":"10.1016/j.jddst.2025.107964","url":null,"abstract":"<div><div>Chronic wounds remain a significant clinical challenge, often with prolonged inflammation and impaired healing. Electrical stimulation is a promising therapeutic modality for accelerating wound repair, though it lacks definitive clinical evidence. Polyvinylidene fluoride (PVDF) nanofibers, owing to their piezoelectric β-phase, can generate bioelectric cues when mechanically deformed, potentially enhancing tissue repair. Electrospun PVDF nanofibrous dressings were fabricated and characterized (SEM, FTIR, tensile testing, WVTR, haemolysis). A full-thickness skin wound model in Sprague–Dawley rats was employed to assess the therapeutic efficacy of PVDF dressings in combination with low-intensity vibration therapy. Macroscopic wound closure, histology (H&amp;E, Masson's trichrome), immunohistochemistry (CK-14, Collagen IV, TGF-β), and serum cytokines (IL-6, TNF-α) were assessed over 14 days. The PVDF nanofibers displayed a uniform diameter (∼145 nm), high β-phase content (58 %), with excellent biocompatibility, acceptable haemolysis rates, and optimal WVTR for wound healing. In vivo, the PVDF + vibration group enhanced wound closure, with almost complete re-epithelialization, dense granulation tissue, and markedly reduced scarring by day 14. Histology showed well-organized dermal collagen, reconstitution of skin appendages, and robust neoangiogenesis. Immunohistochemistry revealed marked upregulation of CK-14 and Collagen IV, accompanied by attenuated TGF-β expression. Inflammatory cytokines were significantly lower in the PVDF + vibration group, indicating attenuated inflammation and improved immune regulation. Synergistic integration of piezoelectric PVDF nanofibers with mechanical vibration significantly enhances wound healing by promoting re-epithelialization, angiogenesis, collagen organization, and immune modulation. This dual-modality offers a promising bioelectrical–mechanical therapeutic nanoplatform for wound management.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107964"},"PeriodicalIF":4.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eudragit S100-based nanofiber membranes for pH-triggered co-release of iridium nanozymes and roxithromycin in antioxidant and antibacterial therapy","authors":"Limo Wang,&nbsp;Danfeng Jian,&nbsp;Bingjie Xu,&nbsp;Zhiye Qiu,&nbsp;Yujie Gao,&nbsp;Jindan Wu","doi":"10.1016/j.jddst.2025.107970","DOIUrl":"10.1016/j.jddst.2025.107970","url":null,"abstract":"<div><div>The vicious cycle of reactive oxygen species (ROS) overload and bacterial infection critically impedes diabetic wound healing. While nanozyme-antibiotic dressings offer therapeutic potential, their uncontrolled agent release remains a key challenge. In this study, a functional nanofiber membrane (EIPR) based on the pH-sensitive polymer Eudragit S100 was fabricated via coaxial electrospinning to load iridium nanozymes (Ir NPs-PVP) and roxithromycin (Rox), enabling on-demand release of therapeutic agents for combined antibacterial and antioxidant wound therapy. The obtained dressing displays highly precise and controllable therapeutic agent release characteristics. Rox shows approximately 90 % cumulative release at pH 7.4, while release is suppressed to &lt;8 % at pH 6.0 and 4.5. Notably, the release trend of Ir NPs-PVP mirrors that of Rox, with significantly higher release under alkaline conditions. The results exhibit &gt;97 % eradication of both <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and <em>Escherichia coli</em> (<em>E. coli</em>) coupled with &gt;75 % ROS clearance at pH 7.4. This study presents a novel dual-function system, highlighting the simplicity and efficiency of electrospinning technology, which are key advantages enhancing its scalability for large-scale manufacturing and suitability for clinical wound care translation.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107970"},"PeriodicalIF":4.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly(ethylene glycol) conjugation to glycyl-L-histidyl-L-lysine peptide enhances fibroblast proliferation and wound healing in rats","authors":"Lan Jin ,&nbsp;Da In Sim ,&nbsp;Soo Hyun Kim ,&nbsp;Sukwoo Han ,&nbsp;Wynn Thein ,&nbsp;Dong Hee Na","doi":"10.1016/j.jddst.2025.107969","DOIUrl":"10.1016/j.jddst.2025.107969","url":null,"abstract":"<div><div>Glycyl-L-histidyl-L-lysine (GHK) has been shown to promote wound healing by enhancing collagen synthesis in fibroblasts. Although lipidated GHK, such as palmitoyl-GHK, is widely used in cosmetics, there are few studies on the clinical use of GHK conjugated with hydrophilic polymers such as poly(ethylene glycol) (PEG). Therefore, herein, we investigated the effect of PEG conjugation to the N-terminal amine of GHK on cell proliferation and <em>in vitro</em>/<em>in vivo</em> wound healing. N-terminal site-specific PEGylation was performed via a reductive amination reaction using aldehyde-activated PEG under mild acidic conditions. The biological activities of the PEGylated GHKs were assessed using cell proliferation and wound healing assays. Notably, each N-terminally PEGylated GHK (PEG-GHK) promoted cell proliferation and stimulated type I collagen synthesis in Hs68 fibroblast cells. Three PEG-GHK species prepared by using PEG of different molecular weights (2, 5, and 10 kDa); among them, 5 kDa-PEG-conjugated GHK (PEG5K-GHK) showed the highest stimulatory effect on cell proliferation and type I collagen synthesis. The cell migration assay confirmed that PEG5K-GHK treatment significantly accelerated <em>in vitro</em> wound healing relative to treatment with non-PEGylated GHK. <em>In vivo</em> experiments using rats showed that PEG5K-GHK treatment for 10 days significantly increased wound closure percentage compared with GHK treatment. Conclusively, these study findings demonstrate that PEG conjugation may enhance the cell proliferation and wound healing effects of GHK.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107969"},"PeriodicalIF":4.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of thermoresponsive quercetin-nanoemulgel eye drop on VEGF-A–induced corneal neovascularization: In vitro and in vivo investigations","authors":"La Ode Muh Julian Purnama ,&nbsp;Adryan Fristiohady ,&nbsp;Witchuda Payuhakrit ,&nbsp;Rathapon Asasutjarit","doi":"10.1016/j.jddst.2025.107968","DOIUrl":"10.1016/j.jddst.2025.107968","url":null,"abstract":"<div><div>Corneal neovascularization (CNV) is a sight-threatening condition with the growth of blood vessels into cornea, which is generally induced by VEGF-A. Recently, the potential of quercetin against VEGF-A activities in the eye has been reported. Unfortunately, its lipophilicity usually causes poor oral bioavailability and insufficient concentrations in the eye tissues. We thus developed formulations of thermoresponsive quercetin nanoemulgel (TQNG) that contained an oil in water quercetin nanoemulsion and a poloxamers-based gel for local treatment of the posterior eye segment neovascularization. Although its <em>in vitro</em> activities against VEGF-A had already been reported, there is a lack of <em>in vivo</em> evidence to support the ability of TQNG to be applied for the treatment of ocular neovascularization. Furthermore, in order to expand its applications for the anterior eye segment neovascularization, TQNG was prepared as an eye drop (TQNG-ED) and investigated its activities against CNV. This study thus aimed to investigate activities of TQNG-ED on VEGF-A–induced CNV <em>in vitro</em> and <em>in vivo</em>. TQNG-ED was prepared and sterilized before determining its anti-neovascularization activities in HUVECs and alkali-induced CNV in rats. The results indicated that TQNG-ED was safe to the corneal cell line and the rabbits' eye according to the short time exposure test and the modified Draize test, respectively. It exhibited promising inhibitory activities on VEGF-A–induced tube formation in HUVECs and CNV in alkali-burned rats' cornea via inhibition of VEGF-A activities and downregulation of VEGF-A receptors. Consequently, TQNG-ED could be accepted as a potential topical therapy of CNV for further clinical studies.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107968"},"PeriodicalIF":4.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of elastic vesicle systems containing diclofenac sodium - in vitro and in vivo evaluation for the treatment of actinic keratosis","authors":"Emre Tunçel ,&nbsp;Serdar Tort ,&nbsp;Sevtap Han ,&nbsp;Çiğdem Yücel ,&nbsp;Figen Tırnaksız","doi":"10.1016/j.jddst.2025.107965","DOIUrl":"10.1016/j.jddst.2025.107965","url":null,"abstract":"<div><div>Dermal drug delivery has recently become a prominent topic for the topical treatment of skin-specific diseases such as actinic keratosis. In skin-related diseases, increased efficacy and reduced side effects can be achieved by increasing the amount of drug accumulated in the target tissue and reducing systemic exposure. In this study, elastic vesicular system formulations were developed to increase the penetration and accumulation of diclofenac sodium in the skin for the treatment of actinic keratosis. The vesicle systems containing diclofenac sodium, Lipoid S100, cholesterol, Transcutol CG, oleic acid, and hyaluronic acid were produced by the film hydration method and characterized in terms of vesicle size, polydispersity index, zeta potential, encapsulation efficiency, viscosity, morphology, and elasticity. Cytotoxicity and ex vivo skin permeation/skin accumulation studies were also performed on the optimum formulations. In ex vivo studies, the selected optimum vesicle system formulation (V4, which contained 20 mg of diclofenac sodium, 125 mg of Lipoid S100, 62.5 mg of cholesterol, and 30 mg of Transcutol CG), which provided the highest drug accumulation in the rat skin, was used in stability and in vivo studies. It was found that V4 was stable for 3 months at 5 °C. In the in vivo studies, a xylene-induced ear edema model was utilized. The efficacy of V4 was evaluated, and it was found to be superior to the commercial product. It was concluded that vesicle systems developed can be used in the effective treatment of actinic keratosis.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107965"},"PeriodicalIF":4.9,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paddle attachments to mitigate coning in USP apparatus II","authors":"Hiroyuki Yoshida ,&nbsp;Tokio Morita ,&nbsp;Aoi Inagaki ,&nbsp;Naomi Tomita ,&nbsp;Yoji Sato","doi":"10.1016/j.jddst.2025.107962","DOIUrl":"10.1016/j.jddst.2025.107962","url":null,"abstract":"<div><div>In dissolution testing using USP Apparatus II, the coning phenomenon, in which the formulation accumulates beneath the paddle, can impair the accurate assessment of the drug dissolution behavior. This study aimed to develop a novel paddle attachment that can be easily installed on a compendial paddle and vessel to mitigate coning under standard dissolution conditions (50 rpm). Cylindrical and conical attachments were designed using 3D printing and installed on a compendial paddle. The effects of multiple pharmaceutical products, including USP prednisone tablets, levofloxacin fine granules, and atorvastatin calcium tablets, were evaluated. The minimum paddle speed required to eliminate coning was determined for standard particles with different densities. Similarity of dissolution profiles was assessed by calculating f₂ values, compared with profiles obtained using apex vessels of varying heights. The newly developed attachments successfully reduced coning effects and improved the dissolution rates of the formulations. The conical attachments exhibited additional improvements by modifying the local hydrodynamics. The dissolution improvement was diameter-dependent; larger diameters and conical attachments enhanced the dissolution more effectively. Attachments with a clearance of 2 mm from the bottom of the vessel provide sufficient cone mitigation without contact with the vessel base. f₂ analysis confirmed that the dissolution profiles using the paddle attachments were comparable to those achieved with apex vessels of varying heights. This novel paddle attachment provides an exploratory hydrodynamic tool for mitigating coning during dissolution testing, allowing controlled evaluation of formulation-dependent dissolution behavior under standard paddle conditions.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107962"},"PeriodicalIF":4.9,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fabrication and characterization of tannic acid-reinforced pullulan-based hydrogel films for wound healing applications","authors":"Sahar Babaei ,&nbsp;Maedeh Mohammadi ,&nbsp;Sepideh Hamedi ,&nbsp;Ghasem Najafpour Darzi ,&nbsp;Hossein Najafzadehvarzi","doi":"10.1016/j.jddst.2025.107958","DOIUrl":"10.1016/j.jddst.2025.107958","url":null,"abstract":"<div><div>Current wound dressings often fail to control infection and inflammation. To address these limitations, bioactive hydrogel films can be designed to support the healing process. In this study, novel multifunctional pullulan-based hydrogel films incorporating xanthan gum (XG), zinc oxide nanoparticles (ZnO NPs) and various concentrations of tannic acid (TA) were fabricated using solvent-casting approach. The hydrogel films exhibited high swelling capacities ranging from 3568 ± 461 % to 6690 ± 101 %, facilitating rapid hemostasis and minimizing exudate. Mechanical strength increased with TA concentration, ranging from 12.94 ± 0.66 MPa to 18.60 ± 0.56 MPa. Water vapor transmission rates (WVTR), between 562.63 ± 12.6 and 766.45 ± 29.5 g/m²/day, indicated the films’ capacity to retain a moist environment. Antibacterial tests demonstrated that ZnO-reinforced films exhibited excellent bactericidal activity against <em>E. coli</em> (86.88 %) and <em>S. aureus</em> (92.80 %), crucial for preventing wound infections. Biocompatibility was confirmed through cytotoxicity and hemolysis tests, with human fibroblast cell viability above 85 %, and scratch assays showed accelerated wound closure (76.6 %) compared to the control (57.3 %), likely due to the synergetic effect of pullulan, XG, and TA in promoting fibroblast migration. Significant reductions in IL-1β and IL-6 levels confirmed anti-inflammatory efficacy. Finally, <em>in vivo</em> wound-healing assessments and histological analyses revealed substantially improved tissue repair and accelerated wound closure in the treated groups compared to the control. Notably, the interaction between TA and ZnO NPs enhanced mechanical and antioxidant performance and controlled ZnO release, minimizing cytotoxicity. These findings indicate that the developed hydrogel films are favorable candidates for wound dressing.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107958"},"PeriodicalIF":4.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The development of ciclesonide dry powder inhalation and preliminary in vivo pharmacokinetic studies in rats","authors":"Mengcai Shi ,&nbsp;Jingxin Sun ,&nbsp;Yidong Yan ,&nbsp;Jishan Quan","doi":"10.1016/j.jddst.2025.107921","DOIUrl":"10.1016/j.jddst.2025.107921","url":null,"abstract":"<div><div>The present study aimed to develop a stabilized ciclesonide (CIC) dry powder inhalation (DPI) and investigate its pharmacokinetic profile in rats. The impactor-sized mass, fine particle fraction (FPF), and delivered dose uniformity of the CIC DPI were used as indicators to design the formulation composition and process parameters. The CIC DPI demonstrated high-efficiency lung deposition (FPF: 50 %–60 % via NGI). Stability testing was conducted over 3 months, and the recommended quality standards were met, exhibiting satisfactory stability under both long-term and intermediate conditions. The CIC DPI and solution were given to rats by pulmonary inhalation and intravenous administration, respectively, to investigate the pharmacokinetic behavior of the drug. Compared with intravenous administration (CIC C_max: 412.42 ng/mL; des-CIC C_max: 43.22 ng/mL), the plasma C_max values in rats following inhalation were significantly lower (CIC C_max: 5.72 ng/mL; des-CIC C_max: 1.47 ng/mL). This &gt;96 % reduction in systemic peak exposure demonstrates the critical advantage of inhaled delivery: minimizing off-target effects while maintaining therapeutic lung concentrations. The concentrations of CIC and Des-CIC measured in lung tissue at the 3-h time point after inhalation were 39.8-fold and 14.0-fold greater, respectively, than those measured after intravenous administration. CIC DPI had significantly lower bioavailability than the CIC solution after injection, which could be helpful for delivery of drugs into the lungs, thus improving effectiveness and decreasing adverse effects. The method described in this paper enables effective preparation of CIC DPI. The optimized formulation complies with European Pharmacopoeia content uniformity standards (A+2.4S &lt; 15), achieves 50 %–60 % FPF, and maintains critical quality attributes under long-term/accelerated stability conditions, supporting its potential as a CIC DPI product. This study lays a foundation for the development and application of CIC DPI.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107921"},"PeriodicalIF":4.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of manufacturing process, lot-to-lot variations and storage stability on the free radical generation in pharmaceutical polymer (polyvinylpyrrolidone)","authors":"Isha Saraf ,&nbsp;Varun Kushwah ,&nbsp;Nathalie Lindbichler ,&nbsp;Santosh Kumar Kushwaha ,&nbsp;Ayush Dubey ,&nbsp;Dmytro Neshchadin ,&nbsp;Georg Gescheidt ,&nbsp;Amrit Paudel","doi":"10.1016/j.jddst.2025.107953","DOIUrl":"10.1016/j.jddst.2025.107953","url":null,"abstract":"<div><div>In the present investigation we have reported the impact of different processes, commonly used in the development of formulations, on the generation of free radicals. Polyvinylpyrrolidone (PVP) polymer is used as a model excipient. PVP is commonly used as a carrier in pharmaceutical drug delivery systems. PVP is synthesized via radical polymerization reaction of the N-vinylpyrrolidone monomer using peroxides. The peroxide, as a residual impurity, due to the manufacturing process and storage conditions have the tendency to develop free radicals. The free radicals generated are chemically very active and thus reacts with the API resulting in the formation of degraded products. The free radicals generated via different process were then quantified using spin trapping and electron paramagnetic resonance (EPR). The developed radicals were trapped via 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and transformed into a stable nitroxide radicals. Those persistent nitroxide radicals were then quantified using the calibration curve obtained by the observation of variable concentrations of the reference 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy radicals (TEMPOL). The free radical concentration was found to be significantly higher in case of the samples (with non-zero initial levels of free radicals) exposed under pressurized thermal oxidation as compared to the drying and milling. However, in case of the PVP having zero free radicals content, the free radical concentration was found to be higher in samples treated with milling followed by pressurized thermal oxidation. Thus, the free radical concentration generated was found to be primarily dependent on the initial level of free radicals present in the raw material, independent of PVP chain length. Further, the impact of lot-to-lot variation and storage stability conditions were also investigated, demonstrating changes in free radical concentration on incubating the samples at RT and accelerated stability conditions. There is dearth of research work published in the multifaceted research domain comprising free radical chemistry, polymer science and pharmaceuticals. Thus, the present investigation could act as the pivotal link to establish the relation between the drug product degradation and free radical concentration.</div></div>","PeriodicalId":15600,"journal":{"name":"Journal of Drug Delivery Science and Technology","volume":"116 ","pages":"Article 107953"},"PeriodicalIF":4.9,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145881033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}