Cristina Yus , Teresa Alejo , Cristina Quílez , Silvia Irusta , Diego Velasco , Manuel Arruebo , Victor Sebastian
{"title":"Development of a hybrid CuS-ICG polymeric photosensitive vector and its application in antibacterial photodynamic therapy","authors":"Cristina Yus , Teresa Alejo , Cristina Quílez , Silvia Irusta , Diego Velasco , Manuel Arruebo , Victor Sebastian","doi":"10.1016/j.ijpharm.2024.124951","DOIUrl":"10.1016/j.ijpharm.2024.124951","url":null,"abstract":"<div><div>At the present time, owing to the extremely high growth of microbial resistance to antibiotics and, consequently, the increased healthcare associated costs and the loss of efficacy of current treatments, the development of new therapies against bacteria is of paramount importance. For this reason, in this work, a hybrid synergetic nanovector has been developed, based on the encapsulation of a NIR (near infrared) photosensitive molecule (indocyanine green, ICG) in biodegradable polymeric nanoparticles (NPs). In addition, copper sulfide nanoparticles (CuS NPs), optically sensitive to NIR, were anchored on the polymeric nanoparticle shell in order to boost the generation of reactive oxygen species (ROS) upon NIR irradiation. As a result, the nanohybrid synthesized material is capable to generate ROS on demand when exposed to a NIR laser (808 nm) allowing for the repeated triggering of ROS production upon NIR light exposure. After each irradiation, the ROS generated were able to eliminate pathogenic bacteria, as it was demonstrated <em>in-vitro</em> with three bacterial strains, <em>Staphylococcus aureus</em> ATCC 25923 used as a reference strain <em>(S. aureus</em>), <em>S. aureus</em> USA300 (methicillin-resistant<!--> <!-->strain, MRSA) and GFP-expressing antibiotic-sensitive <em>S. aureus</em> (methicillin-sensitive strain, MSSA). Finally, the effect of the hybrid NPs in the skin bed was tested on a plasma-derived <em>in vitro</em> skin model. Fluorescence and histological images showed the presence of CuS NPs all over the dermal layer lacking epidermis of the skin construct. Thus, the <em>in vitro</em> model facilitated the prediction of the nanovector’s behavior in a human skin equivalent, showcasing its potential application against topical infections after wounding.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124951"},"PeriodicalIF":5.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638954","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}
Camila Fernanda Rodero , Marcela Tavares Luiz , Mariana Rillo Sato , Fernanda Boni , Guilherme F.S. Fernandes , Jean Leandro dos Santos , Ana Luisa Martinez-Lopez , Juan M. Irache , Marlus Chorilli
{"title":"Rapamycin-loaded nanostructured lipid carrier modified with folic acid intended for breast cancer therapy","authors":"Camila Fernanda Rodero , Marcela Tavares Luiz , Mariana Rillo Sato , Fernanda Boni , Guilherme F.S. Fernandes , Jean Leandro dos Santos , Ana Luisa Martinez-Lopez , Juan M. Irache , Marlus Chorilli","doi":"10.1016/j.ijpharm.2024.124954","DOIUrl":"10.1016/j.ijpharm.2024.124954","url":null,"abstract":"<div><div>Breast cancer stands as the most common form of malignancy among women globally, and it showcases commendable rates of cure when detected in early-stage and non-metastatic conditions. To overcome drug resistance and side effects observed in conventional chemotherapy, the present study aims to deliver rapamycin (RAP), a mTOR protein inhibitor, into a nanostructured lipid carrier (NLC) functionalized with folic acid for promoting active targeting to breast cancer cells. In the first step, the synthesis of 1,2-distearoyl-<em>sn</em>-glycero-3-phosphatidylethanolamine-<em>N</em>-[amino(polyethylene glycol)-2000] (ammonium salt) with folic acid (DSPE-PEG<sub>2000</sub>-FA) was successfully performed and characterized by UV spectroscopy, nuclear magnetic resonance, and infrared spectroscopy. Then, the folic acid-modified NLC loaded with RAP (FA-NLC-RAP) and the unmodified formulation (NLC-RAP) was developed and displayed a size of about 100 nm, negative surface charge, and high RAP encapsulation efficiency (94.92 % and 85.72 %, respectively). In vitro studies suggested that FA-NLC-RAP exhibited a higher degree of internalization in cancer cells (MCF-7) than in normal cells (MCF-10A), demonstrating the potential of folic acid as a ligand for promoting active targeting of RAP for breast cancer cells through folate receptors overexpressed in tumor cells FA-NLC-RAP significantly reduced tumor cell viability, similarly to that observed with the RAP solution. The release profile of the formulation was prolonged. Finally, studies in <em>Caenorhabditis elegans</em> evidenced the safety of FA-NLC-RAP characterized by a complete absence of toxicity in this animal model. Therefore, the findings imply that FA-NLC-RAP holds considerable promise for the treatment of breast cancer.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"668 ","pages":"Article 124954"},"PeriodicalIF":5.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620570","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}
Vasundhara Tyagi , Valerie G.A. Suter , Somnath Kandekar , Maria Lapteva , Yogeshvar N. Kalia
{"title":"Development and biopharmaceutical evaluation of aqueous micelle based corticosteroid formulations for topical treatment of oral lichen planus","authors":"Vasundhara Tyagi , Valerie G.A. Suter , Somnath Kandekar , Maria Lapteva , Yogeshvar N. Kalia","doi":"10.1016/j.ijpharm.2024.124949","DOIUrl":"10.1016/j.ijpharm.2024.124949","url":null,"abstract":"<div><div>The dearth of approved products to treat oral lichen planus (OLP) compels off-label use of dermatological corticosteroid formulations not optimized for indications in the oral cavity. The aims of this study were to develop aqueous micelle based formulations of triamcinolone acetonide (TA) and fluocinonide (FLU), using D-tocopheryl polyethylene glycol succinate, and to investigate corticosteroid delivery to the epithelium-lamina propria junction region – the anatomical target for OLP treatment – in comparison to that from marketed products. Total mucosal deposition of TA after application of Kenacort® A Orabase® (0.1 % TA) and micellar hydrogel (0.1 %) was 242.1 ± 68.5 and 5936.7 ± 1269.6 ng/cm<sup>2</sup>, respectively. For FLU, deposition after application of Novoter (0.05 % FLU) and micellar hydrogel (0.05 %) was 617.1 ± 126.5 and 2580.0 ± 285.5 ng/cm<sup>2</sup>, respectively. A buccal biodistribution study showed that application of micelle hydrogels under occlusion for 30 min delivered 117.0 ± 15.6 ng/cm<sup>2</sup> and 225.6 ± 36.7 ng/cm<sup>2</sup>, of TA and FLU, respectively, to the epithelium-lamina propria junction region. In contrast, the amounts deposited after applying Kenacort® A Orabase® and Novoter, were < LOQ. The results demonstrated that TPGS-based micelles improved mucosal bioavailability of TA and FLU in the epithelium-lamina propria junction region and might serve to improve topical OLP therapy.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124949"},"PeriodicalIF":5.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620547","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}
Zhou Lu , Mingsong Shi , Xueting Zheng , Yuanyuan Liang , Jiali Wang , Zhiyan Zou , Rui Luo , Maosen Feng , Xia Yang , Yan Zhou , Xiaoan Li
{"title":"Preclinical evaluation of 89Zr/177Lu-labeled amatuximab for theranostic application in pancreatic ductal adenocarcinoma","authors":"Zhou Lu , Mingsong Shi , Xueting Zheng , Yuanyuan Liang , Jiali Wang , Zhiyan Zou , Rui Luo , Maosen Feng , Xia Yang , Yan Zhou , Xiaoan Li","doi":"10.1016/j.ijpharm.2024.124946","DOIUrl":"10.1016/j.ijpharm.2024.124946","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) remains a significant clinical challenge, urgently requiring effective intervention strategies. In recent years, the application of radiopharmaceuticals has emerged as a promising modality for the accurate diagnosis and treatment of malignancies. Due to its high expression on pancreatic cancer cells, mesothelin (MSLN) has become an appealing target for radioimmunotherapy (RIT). In this study, we report the development of a novel radiotracer by conjugating amatuximab with zirconium-89 (<sup>89</sup>Zr) to facilitate the non-invasive detection of MSLN expression. Immuno-positron emission tomography (immunoPET) imaging demonstrated a specific accumulation of <sup>89</sup>Zr-DFO- amatuximab in PANC-1-MSLN tumors. Subsequently, Lutetium-177 (<sup>177</sup>Lu)-labeled amatuximab was utilized for MSLN- targeted radioimmunotherapy (RIT), resulting in a significant suppression of PANC-1-MSLN xenograft growth. Furthermore, in vivo studies indicated that <sup>177</sup>Lu-DOTA-amatuximab exhibited limited side effects. The development of <sup>89</sup>Zr/<sup>177</sup>Lu-labeled amatuximab may provide novel insights into the formulation of precision diagnostic and therapeutic strategies for MSLN- overexpressing tumors, including PDAC.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124946"},"PeriodicalIF":5.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620568","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}
{"title":"Coamorphous systems of rebamipide: Selection of amino acid coformers based on protein-ligand docking, in vitro assessment and study of interactions by computational and multivariate analysis","authors":"Abhishek Sharma , Soumyajit Dey , Nagamalli Naga Sidhartha , Saurabh Shah , Rekha Sapkal , Saurabh Srivastava , Amol G. Dikundwar","doi":"10.1016/j.ijpharm.2024.124955","DOIUrl":"10.1016/j.ijpharm.2024.124955","url":null,"abstract":"<div><div>Three coamorphous systems of Rebamipide (REB) with the amino acids namely, Tryptophan (TRP), Phenylalanine (PHE) and Arginine (ARG) are reported. A unique approach for the virtual screening of amino acid coformers is presented by employing molecular docking studies based on interactions of the drug molecule with various amino acid fragments in the drug-receptor cocrystal structure. Successful formation of stable coamorphous systems with ARG, TRP and PHE served as the proof-of-concept along with negative benchmarking standards Histidine and Aspartic acid, wherein coamorphous systems could not be obtained despite multiple trials which resulted in crystalline physical mixtures. The coamorphous systems were characterized by a halo pattern in Powder XRD and a single glass transition temperature (Tg) in modulated DSC. Physical stability assessments of the coamorphous systems showed direct correlation of Tg with the observed stability of the amorphous phase which was found in the order ARGREB > TRPREB ≥ PHEREB. To determine the specific functional groups engaged in the interactions, multivariate analysis was performed on the FTIR spectra. These interactions were further validated by DFT and QTAIM analysis, which revealed key noncovalent interactions in the three coamorphous systems. All three coamorphous systems showed excellent release profiles of the API as demonstrated by the f2 and DE parameters in the order ARGREB ≥ TRPREB > PHEREB ≥ amorphous drug, far exceeding that of the crystalline drug. The interplay of multivariate analysis and QTAIM can be useful in estimating the interactions within the coamorphous systems which can further contribute to stability and physicochemical properties of the systems.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124955"},"PeriodicalIF":5.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620545","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}
Karl Vorländer , Arno Kwade , Jan Henrik Finke , Ingo Kampen
{"title":"Influence of multiple compression phases during tableting of spray dried Saccharomyces cerevisiae on microbial survival and physical–mechanical tablet properties","authors":"Karl Vorländer , Arno Kwade , Jan Henrik Finke , Ingo Kampen","doi":"10.1016/j.ijpharm.2024.124948","DOIUrl":"10.1016/j.ijpharm.2024.124948","url":null,"abstract":"<div><div>The viability of probiotic microorganisms is essential for their health-promoting effects and must be preserved in the best possible way during the production of the final dosage form, such as tablets. This applies to both drying and tableting. <em>Saccharomyces cerevisiae</em> is spray-dried with suitable protective additives, which were identified in a previous study in which also the influence of the formulation during tableting was investigated. One aspect that has not yet been addressed is the effect of multiple compression, as it is typical with pre- and main compression when using rotary tablet presses. To investigate this, tablets are compressed up to five times. It is shown that when tablet strength and survival are considered together, the application of a pre- and main pressure does not have a significant effect. This facilitates the transferability of findings of compaction studies with a single compression phase. In addition, the data allow to consolidate the mechanism of inactivation of microorganisms during tableting found in previous studies by the same authors. This is based on the porosity reduction, whereby it is shown in the present study that it is irrelevant how this reduction is achieved (change in compression stress or the number of compression cycles).</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124948"},"PeriodicalIF":5.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620552","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}
{"title":"The influence of citrate buffer molarity on mRNA-LNPs: Exploring factors beyond general critical quality attributes","authors":"Burcu Binici , Ankita Borah , Julie A Watts , Daragh McLoughlin , Yvonne Perrie","doi":"10.1016/j.ijpharm.2024.124942","DOIUrl":"10.1016/j.ijpharm.2024.124942","url":null,"abstract":"<div><div>Lipid nanoparticles (LNPs) are crucial in delivering mRNA vaccines and therapeutics. The properties of LNPs can be influenced by the choice of lipids and the manufacturing conditions, such as mixing parameters, lipid concentration, and the type and concentration of the aqueous buffer used. In this study, we investigated the impact of the citrate buffer molarity, the buffer commonly used to dissolve mRNA in the preparation of mRNA-LNPs. We prepared SM-102 LNPs containing firefly luciferase mRNA using citrate buffers at molarities of 50 mM, 100 mM, or 300 mM. Our findings revealed that varying the molarity of the citrate buffer did not significantly affect the particle size when considering the average diameter (z-average or Mode). All formulations exhibited low polydispersity index (PDI) and high encapsulation efficiency. Detailed analysis of particle size sub-populations (D10, D50, and D90) and morphology indicated that citrate buffer concentration might influence lipid packing during LNP production, though these differences were subtle. However, using higher citrate molarity (300 mM) to produce LNPs notably reduced cellular internalisation and <em>in vitro</em> transfection efficiency. This trend was also observed <em>in vivo</em>, where similar expression levels were noted in mice receiving the 50 mM and 100 mM LNP formulations, but lower expression was seen for the 300 mM formulation. Our study highlights the importance of buffer molarity in the aqueous phase during mRNA-based LNP preparation and that generally reported critical quality attributes (CQAs) for LNPs may not detect subtle formulation differences.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"668 ","pages":"Article 124942"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619508","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}
Luyan Shen , Xianzhi Liu , Wencheng Wu , Lin Zhou , Guang Liang , Yi Wang , Wenqi Wu
{"title":"“Aging” in co-amorphous systems: Dissolution decrease and non-negligible dissolution increase during storage without recrystallization","authors":"Luyan Shen , Xianzhi Liu , Wencheng Wu , Lin Zhou , Guang Liang , Yi Wang , Wenqi Wu","doi":"10.1016/j.ijpharm.2024.124943","DOIUrl":"10.1016/j.ijpharm.2024.124943","url":null,"abstract":"<div><div>Developing co-amorphous systems is a promising strategy to improve the water solubility of poorly water-soluble drugs. Most of the studies focused on the initial dissolution rate of the fresh co-amorphous systems, and only physical stability was investigated after storage. However, the maintenance of the enhanced dissolution rate of co-amorphous systems after storage is necessary for further product development. The maintenance of amorphous forms after storage does not always mean the maintenance of the dissolution rate. In this study, indomethacin, arginine, tryptophan, and phenylalanine were used as the model drug and the co-formers to prepare co-amorphous systems and then stored under dry condition and RH 60 ± 5 % condition. No recrystallization was observed after the storage for 40 d and 80 d. Interestingly, both intrinsic dissolution rate (IDR) decrease and unexpected increase after storage were confirmed. The further mixing of IND and the co-former at a molecular level and the moisture changes of the co-amorphous systems during storage were supposed to play important roles in the aging. This study reminds us that the possible dissolution changes (both dissolution decrease and increase) of co-amorphous systems during storage should be carefully considered, though these samples maintained amorphous forms.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124943"},"PeriodicalIF":5.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620527","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":"Cellulose nanocrystals/cellulose nanofibrils-combined astaxanthin nanoemulsion for reinforcement of targeted tumor delivery of gastric cancer cells","authors":"Karuppusamy Shanmugapriya , Hyun Wook Kang","doi":"10.1016/j.ijpharm.2024.124944","DOIUrl":"10.1016/j.ijpharm.2024.124944","url":null,"abstract":"<div><div>Nanoemulsion based nanomaterial (NE) was carried out in the present study to evaluate the efficacy and its antitumor potential of the gastric cancer cells. NE was prepared with astaxanthin/alpha-tocopherol- cellulose nanocrystals/cellulose nanofibrils based nanoemulsions for gastric cancer treatment. The cytotoxic potential was tested against cancer cells and evaluated in terms of its cell proliferation, migration, and cellular uptake by the standard methods. NE was examined for its synergetic effect with photodynamic therapy (PDT) in a xenograft mouse model. The results confirmed the synergetic effect of PDT and NEs in the <em>in vivo</em> animal model. The regulated expression of proteins manifested the reduced toxicity and inhibition of cell proliferation and migration. The antitumor study showed that NE inhibited the growth of human colon cancer <em>in vivo</em>. Immunohistological analysis confirmed the regulation of PI3K/AKT signaling pathway. The present study demonstrates that NEs can enhance anti-cancer effect against human gastric cancer through the immunomodulatory signaling pathway.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"667 ","pages":"Article 124944"},"PeriodicalIF":5.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620543","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}
Anna-Maria Börjesdotter , Hans Bolinsson , Thomas Dagø , Fátima Herranz-Trillo , Umberto Capasso Palmiero , Herje Schagerlöf , Lars Nilsson
{"title":"Lipid nanoparticle properties explored using online asymmetric flow field-flow fractionation coupled with small angle X-ray scattering: Beyond average characterisation","authors":"Anna-Maria Börjesdotter , Hans Bolinsson , Thomas Dagø , Fátima Herranz-Trillo , Umberto Capasso Palmiero , Herje Schagerlöf , Lars Nilsson","doi":"10.1016/j.ijpharm.2024.124940","DOIUrl":"10.1016/j.ijpharm.2024.124940","url":null,"abstract":"<div><div>This study employs asymmetric flow field-flow fractionation online coupled with small angle X-ray scattering at a synchrotron beamline, along with multiple downstream detectors, including multi-angle light scattering, dual wavelength UV and dRI. This setup enables size-resolved characterization of lipid nanoparticles, allowing for a detailed comparison between empty and cargo-loaded lipid nanoparticles intended for nucleic acid delivery. Batch-mode characterization techniques, including cryogenic transmission electron microscopy and dynamic light scattering, alongside collection of fractions for offline characterization with liquid chromatography-charged aerosol detection, allowed for determination of the particle morphology, hydrodynamic radius, and the lipid composition over the size distribution. Cargo-containing and empty lipid nanoparticles show differences in density, and loaded particles exhibit a broader size distribution and a higher frequency of blebs at the surface. Both samples consist of spherical core–shell structured particles, with no distinguishable internal structure. A pivotal finding, often assumed until now, is that the mole fraction of each individual lipid component closely matches the original formulation. This work contributes to a more detailed understanding of lipid nanoparticles, supporting their continued development and rational design in medical applications.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":"668 ","pages":"Article 124940"},"PeriodicalIF":5.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142620553","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}