International Journal of Pharmaceutics最新文献

{"title":"Screening and preparation of curcumin nano-formulations combined with dissolving microneedles on the application in the effective treatment of psoriasis","authors":"Peng Xu ,&nbsp;Kun Xu ,&nbsp;Jiayin Li ,&nbsp;Aoxue Liu ,&nbsp;Wei Xiao ,&nbsp;Lin Sun","doi":"10.1016/j.ijpharm.2025.125528","DOIUrl":"10.1016/j.ijpharm.2025.125528","url":null,"abstract":"<div><div>Psoriasis, a prevalent immunoinflammatory skin condition, is characterized by abnormal skin thickening, which complicates traditional topical drug delivery and hinders drug penetration. Our goal is to enhance the efficacy of psoriasis treatment by developing a transdermal drug formulation. Microneedles (MNs) can improve treatment outcomes by increasing the absorption of topical medications through skin penetration. Curcumin (Cur), a natural anti-inflammatory, antioxidant, and immunomodulatory small molecule with water-insoluble properties, shows promise for psoriasis relief. In this research, three Cur nano-formulations (NFs) were screened and prepared using antisolvent and ethanol injection methods, with one being dispersed into hyaluronic acid (HA) dissolving MNs. A transdermal nano-MNs delivery system was constructed using a double-layer centrifugation technique. This co-delivery system overcame Cur’s solubility issues, poor absorption, and instability, allowing targeted and efficient delivery of Cur-NFs to the skin without being hindered by the skin barrier. <em>In vitro</em> studies demonstrated that Cur-NF dissolving MNs possess adequate mechanical properties for skin implantation, exhibit rapid dissolution, and achieve an effective drug release rate of 73 % within 6 h. Pharmacodynamic evaluations demonstrated that the MNs system effectively ameliorated key psoriatic skin manifestations. Notably, MNs treatment significantly reduced the Psoriasis Area and Severity Index (PASI) score from 12.0 ± 0.0 (model group) to 4.7 ± 0.5 (<em>p</em> &lt; 0.05), alongside a marked suppression of pro-inflammatory cytokines, including TNF-α, IL-17, IL-22, and IL-23, compared to untreated psoriatic controls. Therefore, the composite dissolving MNs delivery system loaded with Cur-NFs represents a promising approach for psoriasis treatment.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125528"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734791","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}

{"title":"Development and adhesion evaluation of transdermal rotigotine patches utilizing 3D-printed skin-mimicking substrate, solid-state NMR, and ATR-FTIR techniques.","authors":"Arvind Bagde, Keb Mosley-Kellum, Sungsool Wi, Nisarg Modi, Satyanarayan Dev, Mandip Singh","doi":"10.1016/j.ijpharm.2025.125522","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125522","url":null,"abstract":"<p><p>Transdermal rotigotine patches, used to treat parkinson's disease, often face challenges in maintaining adequate adhesion, which is crucial for effective drug delivery. Adhesion performance is influenced by environmental conditions such as humidity and temperature, as well as skin characteristics like wrinkles and micro-delaminations that vary with age and sex. Standard adhesion tests using stainless steel (SS) substrates do not accurately mimic human skin, leading to overestimated adhesion strength. This study developed rotigotine matrix transdermal formulations with silicone pressure sensitive adhesive (PSA) and evaluated their adhesion properties at 32 ± 1°C and 75 ± 5 % RH in a stability chamber. Moisture uptake over 24 h was measured using solid-state nuclear magnetic resonance (SSNMR) spectroscopy and attenuated total reflectance-fourier transform infrared- (ATR-FTIR) spectroscopy. Adhesion tests, including probe tack and peel, were performed on SS and 3D-printed acrylonitrile butadiene styrene (ABS) substrates designed with micro-delaminations and wrinkles to simulate skin conditions. In vitro permeation testing (IVPT) studies demonstrated a flux of 10.48 ± 0.61 and 10.03 ± 0.57 μg/h/cm² for formulations with and without mannitol, respectively. SSNMR and ATR-FTIR revealed significant moisture uptake, contributing to adhesion loss. Adhesion forces were significantly lower on ABS compared to SS, with further reductions observed on wrinkled and micro-delaminated surfaces, indicating that SS substrates overestimate adhesion results. This is the first study to combine SSNMR and skin-mimetic substrates for analyzing adhesion loss in transdermal patches, highlighting the potential of moisture-resistant agents like mannitol to enhance patch performance.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125522"},"PeriodicalIF":5.3,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742873","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}

{"title":"Development of a stable fixed-dose combination of Montelukast Sodium and Levocetirizine Dihydrochloride using multi-layering API coating technology.","authors":"Dong-Joon Oh, Seo-Young Shin, Chae-Yong Lim, Yu-Byeong Chae, Jung-Ho Yang, Sung-Joo Hwang","doi":"10.1016/j.ijpharm.2025.125527","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125527","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to develop a combination drug containing Montelukast Sodium and Levocetirizine Dihydrochloride using Multi-Layering API Coating Technology (M-LAC Tech) to prevent chemical interactions, enhance stability, and enable sequential drug release.</p><p><strong>Methods: </strong>A core tablet containing Montelukast Sodium was prepared, followed by a barrier coating layer. Levocetirizine Dihydrochloride was then applied as a drug coating over the barrier layer, ensuring complete separation of the two drugs. M-LAC Tech effectively prevents chemical interactions, overcoming the limitations of conventional single-layer and bilayer tablets. An outer coating was added to protect against environmental factors, resulting in a multi-layered film-coated tablet with improved stability and drug release characteristics.</p><p><strong>Results: </strong>The developed tablet reduced size by 50% compared to bilayer tablets, improving patient compliance. The barrier coating effectively prevented drug interactions, ensuring stability, while sequential drug release reduced AUC variability and shortened T_max, enhancing absorption and efficacy. Compared to the reference \"tablet-in-capsule\" formulation, which releases both drugs simultaneously, the M-LAC Tech tablet demonstrated superior pharmacokinetic properties through controlled sequential release.</p><p><strong>Conclusion: </strong>M-LAC Tech enabled the stable incorporation of two drugs in a single dosage form, achieving the smallest tablet size among similar formulations. The technology's ability to block drug interactions and optimize release profiles provides significant clinical advantages. These findings highlight the potential of M-LAC Tech in advancing combination drug development.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125527"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742885","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}

{"title":"Intraluminal enzymatic hydrolysis of API and lipid or polymeric excipients.","authors":"Zahari Vinarov, Anette Müllertzx, Hristina Mircheva, Yann Le Gouar, Olivia Menard, Sharon Pradeep Kumar, Amrit Paudel, Didier Dupont, Patrick Augustijns","doi":"10.1016/j.ijpharm.2025.125489","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125489","url":null,"abstract":"<p><p>The role of intraluminal enzymes for the hydrolysis of active pharmaceutical ingredients (API), prodrugs and pharmaceutical excipients will be reviewed. Carboxylesterases may hydrolyze ester-based API, prodrugs and ester-bond containing polymer excipients, whereas lipases digest lipid formulation excipients, such as mono-, di- and triglycerides. To clarify the conditions that should be mimicked when designing in vitro studies, we briefly review the upper gastrointestinal physiology and provide new data on the inter-individual variability of enzyme activities in human intestinal fluids. Afterwards, the methodology for studying enzymatic hydrolysis of API, prodrugs, lipid and polymeric excipients, as well as the main results that have been obtained, are summarized. In vitro digestion models used to characterize lipid formulations are well described, but data about the hydrolysis of lipid excipients (including surfactants) has been scarce and contradictory. Data on API and prodrug hydrolysis by esterases is available; however, inconsistent use of enzyme types and concentrations limits structure-stability relationships. Hydrolysis of polymer excipients in the lumen has not been significantly explored, with only qualitative data available for cellulose derivates, polyesters, starches, etc. Harmonization of the methodology is required in order to curate larger enzymatic hydrolysis datasets, which will enable mechanistic understanding and theoretical prediction.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125489"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742895","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}

{"title":"Comparative analysis of tablet dissolution behavior: Batch vs. Continuous direct compression","authors":"Kensaku Matsunami ,&nbsp;Alexander Ryckaert ,&nbsp;Hanne Verrecas ,&nbsp;Ana Filipa Tavares da Silva ,&nbsp;Andrew Anderson ,&nbsp;Håkan Wikström ,&nbsp;Melanie Dumarey ,&nbsp;James Mann ,&nbsp;Thomas De Beer ,&nbsp;Valérie Vanhoorne ,&nbsp;Ashish Kumar","doi":"10.1016/j.ijpharm.2025.125498","DOIUrl":"10.1016/j.ijpharm.2025.125498","url":null,"abstract":"<div><div>Continuous manufacturing offers advantages over traditional batch methods, including agility, efficiency, and sustainability. However, transitioning to continuous manufacturing in process development is challenging due to the need for early adoption of industrial-scale equipment. Conversely, batch processes require extensive scale-up studies before commercialization, which continuous processes can avoid. A more efficient approach is to use batch trials in early development to design formulations and processes for continuous manufacturing, requiring assessment of their transferability.</div><div>This study compares the dissolution behavior of immediate-release tablets manufactured via batch and Continuous Direct Compression (CDC), using ibuprofen, a BCS Class II drug. A Design of Experiments (DoE) approach varied formulation properties and tensile strength, with three methods: i) similarity factor ([f2]), ii) Weibull model fitting and Partial Least Squares (PLS) regression, and iii) Gaussian Process Regression (GPR) to assess the transferability of batch trial data and dissolution models for CDC formulation and process design.</div><div>Dissolution profiles were identical between batch and CDC trials when formulations and tensile strength matched, with differences observed only due to deviations in actual tensile strength. The PLS model indicated minimal impact of operational modes on dissolution behavior. The GPR model based only on batch trial data predicted CDC dissolution profiles with a mean <em>R</em>² of 0.910 and RMSE of 4.88%. Overall, the transferability analysis confirmed the predictive capacity of the developed model using batch trial data on the dissolution behavior of tablets manufactured via a CDC line.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125498"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739361","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}

{"title":"A simplified method to interpret the mechanism of drug release from thin polymeric films by drug diffusivity measurements.","authors":"Karin Korelc, Martina M Tzanova, Anette Larsson, Mario Grassi, Massimiliano Pio Di Cagno, Ingunn Tho","doi":"10.1016/j.ijpharm.2025.125491","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125491","url":null,"abstract":"<p><p>Drug-polymer interactions and their respective affinities provide vital information for developing any polymer-containing drug delivery system, such as oral films. This paper offers a simplified method to estimate the effects of interactions between the drug and polymers in corresponding film formulations using a recently developed Fickian diffusion-based methodology. Poly(vinyl alcohol-co-vinyl acetate) (PVA/PVAc) copolymers were used as film matrix formers. To systematically vary the hydrophilicity of the polymer and drug, PVA/PVAc copolymers (monomer ratios 35:65, 50:50, 74:26, 88:12, 98:2) and model drugs, hydrochlorothiazide and caffeine (with a factor 1:30 in solubility) were used. Drug diffusivities determined in a polymer solution (5 % w/v) were compared to classical in vitro drug release from the films. The drug release rate from films containing copolymers with a lower VA/VAc ratio (35:65, 50:50, and 74:26) was significantly different for the two drugs in the first 30 min. It was found that this diffusivity method provided valuable guidance in assessing drug-polymer affinity, described as the average theoretical partition constant K_m/w between the polymer solution and pure aqueous media. This partition constant could be correlated to the drug release rate and serve as a simple, easy, and inexpensive screening method to provide deeper mechanistic insight into drug release mechanisms. This would allow enhanced sustainability and accelerate the formulation development process by reducing resources needed for the development of film formulations.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125491"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742866","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}

{"title":"Patient in-use, room temperature and accelerated conditions stability evaluation of FDA approved clopidogrel hydrogen sulfate products.","authors":"Bhanu P Dongala, Rizwan Shaikh, Swaroop J Pansare, Sunil K Thota, Ziyaur Rahman, Mansoor A Khan","doi":"10.1016/j.ijpharm.2025.125519","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125519","url":null,"abstract":"<p><p>The objective of the study was to evaluate patient in-use, room temperature, and accelerated conditions stability of FDA-approved products of clopidogrel hydrogen sulfate (CHS). Four products (A, B, C and D) were stored at 25 °C/60 % RH (room temperature), 30 °C/75 % RH (patient in-use) and 40 °C/75 % RH (accelerated) stability conditions for 12 weeks. The products were characterized for physicochemical properties such as hardness, disintegration, assay, impurities, dissolution, Fourier-transformed infrared (FTIR), near-infrared (NIR), hyperspectral imaging, and X-ray powder diffraction (XRPD). Absorption spectroscopic and diffractometry data indicated polymorphic forms present in the products were not identical. Products A and D contained form Ⅱ, while Products B and C contained form Ⅰ of the drug. No form Ⅰ to form Ⅱ and vice-versa transformation was observed in products after exposure to stability conditions. However, an increase in crystallinity was observed with storage conditions especially at 40 °C/75 % RH. Impurity C and dissolution met pharmacopeial specifications. Dissolved drug varied from 95.2 to 97.1 % in 30 min and impurity C content was 0.04-0.57 %. After storage at various conditions, impurity C content increased insignificantly, still met pharmacopeial specification. However, Products stored at 30 °C/75 % RH (patient in-use) and 40 °C/75 % RH failed to meet dissolution specification of 85 % in 30 min due to an increase in crystallinity. In conclusion, FDA approved products of CHS contained different polymorphic forms, and crystallinity may increase on exposure to patient in-use condition which may impact clinical outcomes.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125519"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742854","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}

{"title":"Model-Supported dissolution methods for Modified-Release Products: Enteric-coated versus extended-release ketoprofen tablets","authors":"Mauricio A. García ,&nbsp;Jozef Al-Gousous ,&nbsp;Pablo M. González ,&nbsp;Peter Langguth","doi":"10.1016/j.ijpharm.2025.125524","DOIUrl":"10.1016/j.ijpharm.2025.125524","url":null,"abstract":"<div><div>Drug product development is often a challenging endeavor. However, model-supported dissolution test design trained by appropriate <em>in silico</em> models can lead to considerable reduction in the risk<!--> <!-->of<!--> <!-->failure. Dissolution models have revealed that dissolution of poorly soluble ionizable pharmaceutical particles is slower in biorelevant bicarbonate than compendial buffers. The reason is bicarbonate’s lowered effective pK_a (pk_a,eff), as a consequence of comparable reaction and diffusional times during dissolution. This is not necessarily the case when the drug is formulated as a controlled-release dosage form. In this paper, we explored the differences in dissolution between enteric coated (EC) and extended release (XR) ketoprofen formulations. <em>In vitro</em> dissolution was studied in low molarity buffers to mimic the lowered intestinal bicarbonate pk_a,eff, while their biorelevance was confirmed through <em>in vivo</em> comparative bioavailability studies. Both dissolution in low molarity phosphate and <em>in vivo</em> absorption profiles of EC tablets were sensitive to their coating polymer material. Similarly, XR <em>in vitro</em> dissolution in low molarity media showed discrepancies between formulations, caused by dibasic calcium phosphate in one formulation. Conversely, those <em>in vitro</em> differences were not relevant after the <em>in vivo</em> testing. Mechanistic insights from mass/charge balance modelling suggested that slower diffusional times and small liquid-to-solid ratio in XR dosage forms allow bicarbonate reactions to reach their equilibrium. This results in an enhanced buffer capacity, which was not matched by <em>in vitro</em> low molarity media. Therefore, improvement in biopredictivity of XR dosage forms can be achieved by performing dissolution experiments at high rather than low buffer molarities.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"675 ","pages":"Article 125524"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739458","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}

{"title":"BMSCs laden gelatin methacrylate (GelMA) hydrogel integrating silk fibroin/hydroxyapatite scaffold with multi-layered-oriented pores for enhanced bone regeneration.","authors":"Lu Wang, Jie Kang, Yuanjiao Li, Yijing Xia, Xiujuan Li, Xin Du, Ziruo Yin, Feng Tian, Feng Wu, Bin Zhao","doi":"10.1016/j.ijpharm.2025.125495","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125495","url":null,"abstract":"<p><p>Due to the limited regenerative ability of bone tissue, bone injury repair has always been a complicated problem in clinical treatment. Bone tissue engineering based on cell delivery is an effective method to repair bone defects, but it also puts forward strict requirements on the scaffold used in the repair process and the survival rate of cell inoculation. To address this challenge, we constructed a bone mesenchymal stem cells (BMSCs) laden gelatin methacrylate (GelMA) hydrogel to integrate in silk fibroin (SF) /nano-hydroxyapatite (nHAp) scaffold, building a dual architecture to achieve enhanced angiogenesis and bone regeneration. The GelMA hydrogel prepared by visible photo-crosslinking showed good cell loading capacity, and the multi-layered-oriented pores of the scaffold provided a suitable microenvironment for cell proliferation and nutrient exchange. We further explored the effects of this \"dual-system\" complex on BMSCs and in a critical-sized rat cranial defect model. The results showed that BMSCs@GelMA-SF/nHAp composite scaffold with directional pore structure was more conducive to the repair of skull defects in rats due to the faster rate of vascularization and osteogenesis, indicating the developed gel-scaffold complex would be a promising therapeutic strategy for the repair of bone defects regeneration.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125495"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742870","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}

{"title":"Generation of continuous production of polymeric nanoparticles via microfluidics for aerosolised localised drug delivery.","authors":"Giuseppina Catania, Giulia Guerriero, Naoual Bakrin, Jérémie Pourchez, Ghalia Kaouane, Lara Leclerc, Lionel Augeul, Ragna Haegebaert, Katrien Remaut, David Kryza, Giovanna Lollo","doi":"10.1016/j.ijpharm.2025.125532","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2025.125532","url":null,"abstract":"<p><p>Transferring the production of nanoparticles from laboratory batches to large-scale production for preclinical and clinical applications represents a challenge due to difficulties in scaling up formulations and lack of suitable preclinical models for testing. Here, we transpose the production of hyaluronic acid and polyarginine-based nanoparticles encapsulating the platinum-derivative dichloro(1,2 diaminocyclohexane)platinum(II), from conventional bulk method to continuous production using microfluidics. The microfluidic-based drug delivery system (DDS) is then tested in a customised preclinical setup to assess its suitability for pressurised intraperitoneal aerosol chemotherapy (PIPAC), a locoregional chemotherapy used to treat peritoneal carcinomatosis. PIPAC consists of the aerosolization of drugs under pressure using laparoscopy. In our preclinical setup, two clinical aerosol devices, CapnoPen® and TOPOL®, are used in conjunction with syringe pump to achieve the clinically optimal aerosol droplet size range (25-50 μm). Aerosol droplet sizes of 38 and 64 μm are obtained at upstream pressures of 14.7 and 7.4 bar and flow rates of 0.4 and 1.1 mL/s, for CapnoPen® and TOPOL®, respectively. To study the spatial distribution of the aerosol, our preclinical setup is then coupled to an ex-vivo model (inverted porcine urinary bladder) that mimics the physiological peritoneal cavity environment. The smaller droplet size obtained with CapnoPen® provided more homogeneous aerosol distribution in the bladder cavity, crucial for maximising treatment coverage within the peritoneal cavity. Furthermore, stability studies reveal that nanoparticles maintained their physicochemical properties and anticancer activity post-aerosolization. Overall, this study provides a scalable approach for the production of platinum-derivative-loaded polymeric nanoparticles and demonstrates the suitability of this DDS for PIPAC.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":" ","pages":"125532"},"PeriodicalIF":5.3,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742889","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}