International Journal of Pharmaceutics: X最新文献

{"title":"Spanlastic-laden in situ gel as a promising approach for ocular delivery of Levofloxacin: In-vitro characterization, microbiological assessment, corneal permeability and in-vivo study","authors":"Omnia Ahmed Agha ,&nbsp;Germeen N.S. Girgis ,&nbsp;Mohamed M.A. El-Sokkary ,&nbsp;Osama Abd El-Azeem Soliman","doi":"10.1016/j.ijpx.2023.100201","DOIUrl":"10.1016/j.ijpx.2023.100201","url":null,"abstract":"<div><p>The objective of this study was to encapsulate the antibacterial drug levofloxacin hemihydrate (LF) into spanlastics (SLs) followed by incorporation into gelrite in situ gel to enhance its antibacterial activity and sustain ocular delivery. A combination of Span 60 as main vesicle component and Tweens as an edge activator (EA) was used to prepare SLs using the thin film hydration method. A 3² factorial design was applied to study the effect of formulation variables (ratio of Span 60: EA and type of EA) on SLs characteristics (encapsulation efficiency (EE%), particle size (PS), zeta potential (ZP) and percentage of drug released). In-vitro antimicrobial study was conducted to determine the antibacterial activity of the optimized formula. Finally confocal laser scanning microscopy (CLSM) was applied to monitor SLs corneal penetration. The optimum formulation (F5), contains 240 mg Span 60 and 60 mg Tween 60 as EA. F5 exhibited EE% = 59.7 ± 4.2%, PS = 177.6 ± 1.8 nm, PDI = 0.27 ± 0.022 and ZP = -40.6 ± 0.68 mV. Furthermore, only 39.37 ± 0.72% of LF amount was released after 4 h compared to complete release from drug solution. The apparent permeation coefficient was (14.7 × 10⁻³ cm/h) compared to (9.7 × 10⁻³ cm/h) for LF solution. Moreover, F5 exhibited 200% and 100% increase in the antibacterial efficacy against <em>Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus</em> respectively.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1c/ad/main.PMC10407905.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974092","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":"Polymorphic transitions in flufenamic acid-trehalose composites","authors":"Yuying Pang ,&nbsp;Simon Gaisford ,&nbsp;Oxana V. Magdysyuk ,&nbsp;Gareth R. Williams","doi":"10.1016/j.ijpx.2023.100200","DOIUrl":"10.1016/j.ijpx.2023.100200","url":null,"abstract":"<div><p>The combination of poorly-soluble drugs with small molecule co-formers to generate amorphous solid dispersions (ASDs) has great potential to improve dissolution rate and kinetic solubility, and thus increase the bioavailability of these active ingredients. However, such ASDs are known to be unstable and to crystallise upon storage or heating. In this work, we explore the crystallisation of flufenamic acid (FFA) from ASDs prepared with trehalose. FFA-trehalose mixtures were prepared at a range of <em>w</em>/w composition ratios, heated to melting and crash cooled to form ASDs. They were then subject to a further heat/cool cycle, which was monitored by simultaneous differential scanning calorimetry – X-ray diffraction to observe the phase changes occurring. These varied with the composition of the blend. Upon short-term storage, formulations with low trehalose contents (FFA:trehalose 5:1 <em>w</em>/w) recrystallised into form I FFA, while higher trehalose contents crystallised to FFA form IV. When heated, all FFA trehalose combinations ultimately recrystallised into form I before melting. Upon a second cooling cycle, systems with low trehalose content (FFA:trehalose 5:1 <em>w</em>/w) recrystallised into form IV, while higher trehalose contents led to FFA form I. It is thus clear that even with a single excipient it is possible to control the crystallisation pathway through judicious choice of the formulation parameters.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10410518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9978140","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":"Preparation of chitosan-coated hollow tin dioxide nanoparticles and their application in improving the oral bioavailability of febuxostat","authors":"Junpeng Sun ,&nbsp;Jiaqun Du ,&nbsp;Xiaobang Liu ,&nbsp;Jinyu An ,&nbsp;Yingqiao Li ,&nbsp;Yanan Yu ,&nbsp;Minghui Li ,&nbsp;Li Zheng ,&nbsp;Chao Wu ,&nbsp;Lili Hu","doi":"10.1016/j.ijpx.2023.100199","DOIUrl":"10.1016/j.ijpx.2023.100199","url":null,"abstract":"<div><p>The aim of this study was to design a chitosan-coated hollow tin dioxide nanosphere (CS-HSn) for loading febuxostat (FEB) using an adsorption method to obtain a sustained-release system (CS-HSn-FEB) to improve the oral bioavailability of FEB. The morphological characteristics of hollow tin dioxide nanospheres (HSn) and CS-HSn were analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The hemolysis test and CCK-8 test were used to assess the biosafety of HSn and CS-HSn. Powder X-ray diffraction (PXRD) and differential scanning thermal analysis (DSC) were performed on CS-HSn-FEB to analyze the drug presence status. The dissolution behavior and changes in plasma drug concentration of CS-HSn-FEB were evaluated in vitro and in vivo. Sections of intestinal tissues from SD rats were obtained to observe whether chitosan could increase the distribution of nanoparticles in the intestinal tissues. The results showed that FEB was present in CS-HSn in an amorphous state. Moreover, CS-HSn, with good biosafety, significantly improved the water solubility and oral absorption of FEB, indicating that CS-HSn has great potential to improve the intestinal absorption and oral bioavailability of insoluble drugs.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/c2/main.PMC10384222.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910263","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":"Effect of the amount of cationic lipid used to complex siRNA on the cytotoxicity and proinflammatory activity of siRNA-solid lipid nanoparticles","authors":"Mahmoud S. Hanafy ,&nbsp;Huy M. Dao ,&nbsp;Haiyue Xu ,&nbsp;John J. Koleng ,&nbsp;Wedad Sakran ,&nbsp;Zhengrong Cui","doi":"10.1016/j.ijpx.2023.100197","DOIUrl":"10.1016/j.ijpx.2023.100197","url":null,"abstract":"<div><p>When preparing siRNA-encapsulated solid lipid nanoparticles (siRNA-SLNs), cationic lipids are commonly included to condense and lipophilize the siRNA and thus increase its encapsulation in the SLNs. Unfortunately, cationic lipids also contribute significantly to the cytotoxicity and proinflammatory activity of the SLNs. Previously, our group developed a TNF-α siRNA-SLN formulation that showed strong activity against rheumatoid arthritis unresponsive to methotrexate in a mouse model. The siRNA-SLNs were composed of lecithin, cholesterol, an acid-sensitive stearoyl polyethylene glycol (2000) conjugate, and siRNA complexes with 1,2-dioleoyl-3trimethylammonium-propane (DOTAP), a cationic lipid. The present study was designed to study the effect of the amount of DOTAP used to complex the siRNA on the cytotoxicity and proinflammatory activity of the resultant siRNA-SLNs. A small library of siRNA-SLNs prepared at various ratios of DOTAP to siRNA (i.e., nitrogen to phosphate (N/P) ratios ranging from 34:1 to 1:1) were prepared and characterized, and the cytotoxicity and proinflammatory activity of selected formulations were evaluated in cell culture. As expected, the siRNA-SLNs prepared at the highest N/P ratio showed the highest cytotoxicity to J774A.1 macrophage cells and reducing the N/P ratio lowered the cytotoxicity of the siRNA-SLNs. Unexpectedly, the cytotoxicity of the siRNA-SLNs reached the lowest at the N/P ratios of 16:1 and 12:1, and further reducing the N/P ratio resulted in siRNA-SLNs with increased cytotoxicity. For example, siRNA-SLNs prepared at the N/P ratio of 1:1 was more cytotoxic than the ones prepared at the N/P ratio 12:1. This finding was confirmed using neutrophils differentiated from mouse MPRO cell line. The DOTAP release from the siRNA-SLNs prepared at the N/P ratio of 1:1 was faster than from the ones prepared at the N/P ratio of 12:1. The siRNA-SLNs prepared at N/P ratios of 12:1 and 1:1 showed comparable proinflammatory activities in both macrophages and neutrophils. Additionally, the TNF-α siRNA-SLNs prepared at the N/P ratios of 12:1 and 1:1 were equally effective in downregulating TNF-α expression in J774A.1 macrophages. In conclusion, it was demonstrated that at least in vitro in cell culture, reducing the amount of cationic lipids used when preparing siRNA-SLNs can generally help reduce the cytotoxicity of the resultant SLNs, but siRNA-SLNs prepared with the lowest N/P ratio are not necessarily the least cytotoxic and proinflammatory.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/bd/main.PMC10371828.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294654","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":"Highly protein-loaded melt extrudates produced by small-scale ram and twin-screw extrusion - evaluation of extrusion process design on protein stability by experimental and numerical approaches","authors":"Katharina Dauer ,&nbsp;Kevin Kayser ,&nbsp;Felix Ellwanger ,&nbsp;Achim Overbeck ,&nbsp;Arno Kwade ,&nbsp;Heike P. Karbstein ,&nbsp;Karl G. Wagner","doi":"10.1016/j.ijpx.2023.100196","DOIUrl":"10.1016/j.ijpx.2023.100196","url":null,"abstract":"<div><p>Understanding of generation, extent and location of thermomechanical stress in small-scale (&lt; 3 g) ram and twin-screw melt-extrusion is crucial for mechanistic correlations to the stability of protein particles (lysozyme and BSA) in PEG-matrices. The aim of the study was to apply and correlate experimental and numerical approaches (1D and 3D) for the evaluation of extrusion process design on protein stability. The simulation of thermomechanical stress during extrusion raised the expectation of protein degradation and protein particle grinding during extrusion, especially when TSE was used. This was confirmed by experimental data on protein stability. Ram extrusion had the lowest impact on protein unfolding temperatures, whereas TSE showed significantly reduced unfolding temperatures, especially in combination with kneading elements containing screws. In TSE, the mechanical stress in the screws always exceeded the shear stress in the die, while mechanical stress within ram extrusion was generated in the die, only. As both extruder designs revealed homogeneously distributed protein particles over the cross section of the extrudates for all protein-loads (20–60%), the dispersive power of TSE revealed not to be decisive. Consequently, the ram extruder would be favored for the production of stable protein-loaded extrudates in small scale.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9820477","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":"Sustained release of therapeutic gene by injectable hydrogel for hepatocellular carcinoma","authors":"Shuangta Xu ,&nbsp;Jianya Cai ,&nbsp;Hongwei Cheng ,&nbsp;Wei Wang","doi":"10.1016/j.ijpx.2023.100195","DOIUrl":"10.1016/j.ijpx.2023.100195","url":null,"abstract":"<div><p>Gene therapy has shown remarkable effectiveness in the management of disease like cancer and inflammation as a revolutionary therapeutic. Nonetheless, therapeutic drug target discovery, efficient gene delivery, and gene delivery vehicles continue to be significant obstacles. Due to their effective gene transport capabilities and low immunogenicity, supramolecular polymers have garnered significant interest. Herein, ABHD5 is identified as a potential therapeutic target since it is dysregulated in hepatocellular carcinoma (HCC). Interestingly, the downregulation of ABHD5 could induce programmed death-ligand 1 (PD-L1) expression in liver cancer, which may contribute to the immunosuppression. To overcome the immunosuppression caused by PD-L1, an injectable hydrogel is designed to achieve efficient abhydrolase domain containing 5 (ABHD5) gene delivery via the host-guest interaction with branched polyethyleneimine-g-poly (ethylene glycol), poly (ethylene oxide) and poly (propylene oxide) block copolymers and α-CD (PPA/CD), demonstrating the capability for sustained gene release. The co-assembly hydrogel demonstrates good biocompatibility and enhanced gene transfection efficiency, efficiently triggering tumor cell apoptosis. Overall, the results of this study suggest that ABHD5 is a potential therapeutic target, and that a host-guest-based supramolecular hydrogel could serve as a promising platform for the inhibition of HCC.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e1/99/main.PMC10336675.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9820479","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":"Chicken embryo model for <i>in vivo</i> acute toxicological and antitumor efficacy evaluation of lipid nanocarrier containing doxorubicin.","authors":"Aline de Cristo Soares Alves, Danieli Rosane Dallemole, Taiane Medeiro Ciocheta, Augusto Ferreira Weber, Samanta da Silva Gündel, Fernanda Visioli, Fabricio Figueiró, Silvia Stanisçuaski Guterres, Adriana Raffin Pohlmann","doi":"10.1016/j.ijpx.2023.100193","DOIUrl":"10.1016/j.ijpx.2023.100193","url":null,"abstract":"<p><p>Nanoencapsulation of chemotherapeutics, including doxorubicin, can endow the formulations with unique properties, such as a decrease in adverse effects and toxicity. The chicken embryo model is an alternative and well-accepted strategy for evaluating the toxicity and efficacy of drugs and nanoformulations. Therefore, this study proposes the development of a new lipid nanocarrier for doxorubicin delivery (NanoLip-Dox) and posterior evaluation of toxicological profile and antitumoral efficacy against a breast tumor in chicken embryos. NanoLip-Dox showed a unimodal particle size (< 150 nm), negative zeta potential (-19.5 mV), absence of drug crystals, drug content of 0.099 mg·mL^-1, and high entrapment efficiency (95%). NanoLip-Dox did not cause toxicity in the chicken embryos; in contrast, doxorubicin hydrochloride induced moderate irritation in the chorioallantoic membrane (at 862.1 μmol·L^-1), a survival rate of 50% (at 1.7 μmol·L^-1), and an increase in aspartate aminotransferase (at 862.1, 344.8, and 172.4 μmol·L^-1). In addition, NanoLip-Dox (at 1.7 μmol·L^-1) showed potent antitumor efficacy with a high tumor remission percentage (40.9 ± 9.7%) compared to the control group (8.6 ± 14.8%). These findings together with the absence of toxicity concerning morphological characteristics, weights of embryos and organs, hematologic parameters, and enzymatic activity (alanine aminotransferase, aspartate aminotransferase, and creatinine) suggest the safety and efficacy of NanoLip-Dox.</p>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10777201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54480555","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":"Formulation, optimization, in-vivo biodistribution studies and histopathological safety assessment of duloxetine HCl-loaded ultra-elastic nanovesicles for antidepressant effect after intranasal and transdermal delivery","authors":"Radwa M.A. Abd-Elal ,&nbsp;Aya M. Essawy ,&nbsp;Maha A. Salem ,&nbsp;Mahitab Elsayed ,&nbsp;Mona G. Khalil ,&nbsp;Eman Abdelhakeem ,&nbsp;Nouran A. Ali ,&nbsp;Mai Ahmed Tawfik","doi":"10.1016/j.ijpx.2023.100194","DOIUrl":"10.1016/j.ijpx.2023.100194","url":null,"abstract":"<div><p>Duloxetine hydrochloride (DUL) is a BCS class-II antidepressant drug, acting via serotonin and norepinephrine reuptake inhibition. Despite high oral absorption, DUL suffers limited bioavailability due to extensive gastric and first-pass metabolism. To improve DUL's bioavailability; DUL-loaded elastosomes were developed, via full factorial design, utilizing various span®60: cholesterol ratios, edge activator types and amounts. Entrapment efficiency (E.E.%), particle size (PS), zeta potential (ZP) and in-vitro released percentages after 0.5 h (Q_0.5h) and 8 h (Q_8h) were evaluated. Optimum elastosomes (DUL-E1) were assessed for morphology, deformability index, drug crystallinity and stability. DUL pharmacokinetics were evaluated in rats following intranasal and transdermal application of DUL-E1 elastosomal gel. DUL-E1 elastosomes [comprising span®60 and cholesterol (1:1) and brij S2 (edge activator; 5 mg)] were optimum with high E.E.% (81.5 ± 3.2%), small PS (432 ± 13.2 nm), ZP (−30.8 ± 3.3 mV), acceptable Q_0.5h (15.6 ± 0.9%), and high Q_8h (79.3 ± 3.8%). Intranasal and transdermal DUL-E1 elastosomes revealed significantly higher C_max (251 ± 18.6 and 248 ± 15.9 ng/mL) at T_max (2 and 4 h) and improved relative bioavailability (≈ 2.8 and 3.1 folds) respectively, in comparison to oral DUL aqueous solution. In-vivo histopathological studies were conducted to ensure the safety of DUL-E1. Elastosomes are promising novel nano-carriers, capable of enhancing the bioavailability of DUL via various routes of administration.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5f/ca/main.PMC10331411.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9812360","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 effect of lung emptying before the inhalation of aerosol drugs on drug deposition in the respiratory system","authors":"Árpád Farkas ,&nbsp;Gábor Tomisa ,&nbsp;Georgina Szénási ,&nbsp;Péter Füri ,&nbsp;Szilvia Kugler ,&nbsp;Attila Nagy ,&nbsp;János Varga ,&nbsp;Alpár Horváth","doi":"10.1016/j.ijpx.2023.100192","DOIUrl":"10.1016/j.ijpx.2023.100192","url":null,"abstract":"<div><p>The amount of drug depositing in the airways depends, among others, on the inhalation manoeuvre and breathing parameters. The objective of this study was to quantify the effect of lung emptying before the inhalation of drugs on the lung doses. Thirty healthy adults were recruited. Their breathing profiles were recorded while inhaling through six different emptied DPI devices without breathe-out and after comfortable or forced exhalation. The corresponding emitted doses and aerosol size distributions were derived from the literature. The Stochastic Lung Model was used to estimate the deposited doses. In general, forceful exhalation caused increased flow rate and inhaled air volume. Increased flow rate led to the increase of the average lung dose for drugs with positive lung dose-flow rate correlation (e.g. Symbicort®: relative increase of 6.7%, Bufomix®: relative increase of 9.2%). For drugs with negative correlation of lung dose with flow rate (all the studied drugs except the above two) lung emptying caused increased (Foster® by 2.7%), almost unchanged (Seebri®, Relvar®, Bretaris®) and also decreased (Onbrez® by 6.6%) average lung dose. It is worth noting that there were significant inter-individual differences, and lung dose of each drug could be increased by a number of subjects. In conclusion, the change of lung dose depends on the degree of lung emptying, but it is also inhaler and drug specific. Forceful exhalation can help in increasing the lung dose only if the above specificities are taken into account.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/64/main.PMC10315997.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10160553","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":"Heparin interferes with the uptake of liposomes in glioma","authors":"Thomas S. van Solinge ,&nbsp;Kristina Pagh Friis ,&nbsp;Killian O'Brien ,&nbsp;Romy L. Verschoor ,&nbsp;Jeroen van Aarle ,&nbsp;Arnold Koekman ,&nbsp;Xandra O. Breakefield ,&nbsp;Pieter Vader ,&nbsp;Raymond Schiffelers ,&nbsp;Marike Broekman","doi":"10.1016/j.ijpx.2023.100191","DOIUrl":"10.1016/j.ijpx.2023.100191","url":null,"abstract":"<div><p>In glioblastoma, a malignant primary brain tumor, liposomes have shown promise in pre-clinical and early phase clinical trials as delivery vehicles for therapeutics. However, external factors influencing cellular uptake of liposomes in glioma cells are poorly understood. Heparin and heparin analogues are commonly used in glioma patients to decrease the risk of thrombo-embolic events. Our results show that heparin inhibits pegylated liposome uptake by U87 glioma and GL261 cells in a dose dependent manner <em>in vitro,</em> and that heparin-mediated inhibition of uptake required presence of fetal bovine serum in the media. In a subcutaneous model of glioma<em>,</em> Cy5.5 labeled liposomes could be detected with <em>in vivo</em> imaging after direct intra-tumoral injection. <em>Ex-vivo</em> analysis with flow cytometry showed a decreased uptake of liposomes into tumor cells in mice treated systemically with heparin compared to those treated with vehicle only.</p></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":null,"pages":null},"PeriodicalIF":4.7,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10319201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9794395","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}