International Journal of Pharmaceutics: X最新文献

{"title":"Prodigiosin hydrogel to promote healing of trauma-infected multidrug-resistant Staphylococcus aureus mice wounds","authors":"Xin Wang,&nbsp;Guangfan Meng,&nbsp;Zongyu Zhang,&nbsp;Jiacheng Zhao,&nbsp;Shaoyu Wang,&nbsp;Dongliang Hua,&nbsp;JingZhang,&nbsp;Jie Zhang","doi":"10.1016/j.ijpx.2024.100306","DOIUrl":"10.1016/j.ijpx.2024.100306","url":null,"abstract":"<div><div>Wound infections caused by Multidrug-resistant <em>Staphylococcus aureus</em> (MRSA) have been regarded as a challenging problem in clinic for the long time. In this study, based on the excellent antimicrobial effect of prodigiosin(PG) and the ability of hydrogel dressing in terms of tissue repair and regeneration, we prepared the PG hydrogel as a treatment for the wound infection induced by MRSA. Rheological tests indicated that PG hydrogel as a semi-solid gel had good mechanical properties. In ex vitro drug permeation studies and dermatokinetic studies showed that PG hydrogel had high PG permeability and were capable of short-term retention in the skin. In addition, in vivo experiments for mouse skin wounds showed that the serum levels of inflammatory factors including IL-β and other inflammatory factors were reduced, the inflammatory infiltration of tissues was reduced, the transcript levels of genes such as COL1A1 were up-regulated at different stages of wound healing, and the relative abundance of genera such as <em>Desulfovibrio</em> was lowered after treatment with PG hydrogel, which facilitated wound healing in mice. Our study would provide a new solution to the clinical shortage of drugs for the treatment of MRSA infection and provide a research basis for improving the comprehensive values of PG.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100306"},"PeriodicalIF":5.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142721322","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":"Trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib for the targeted therapy of HER-2-positive breast cancer","authors":"Xing Liu,&nbsp;Wenwen Shen","doi":"10.1016/j.ijpx.2024.100302","DOIUrl":"10.1016/j.ijpx.2024.100302","url":null,"abstract":"<div><div>In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100302"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658487","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":"Kinetics of elastic recovery in roll compaction","authors":"Martin Lück,&nbsp;Stefan Klinken-Uth,&nbsp;Peter Kleinebudde","doi":"10.1016/j.ijpx.2024.100303","DOIUrl":"10.1016/j.ijpx.2024.100303","url":null,"abstract":"<div><div>Elastic recovery (<span><math><mi>ER</mi></math></span>) has been investigated and discussed extensively in the field of tableting. However, until now only limited data is available regarding <span><math><mi>ER</mi></math></span> in roll compaction. Therefore, a previously established in-line measurement technique was rolled out to further investigate the kinetics of <span><math><mi>ER</mi></math></span> in roll compaction and the effects of specific compaction force (<span><math><mi>SCF</mi></math></span>) and roll speed (<span><math><mi>RS</mi></math></span>). In-line laser triangulation measurements at different positions within a roll rotation as well as measurement over time after the process has been stopped were utilized. Pure microcrystalline cellulose (<span><math><mi>MCC</mi></math></span>) and two placebo powder blend formulations were analysed. Successful fit of the contained <span><math><mi>ER</mi></math></span> profiles emphasized that the <span><math><mi>ER</mi></math></span> on the roll surface is build out of two exponential kinetics. Starting with a dominating fast <span><math><mi>ER</mi></math></span> (<span><math><msub><mi>ER</mi><mi>A</mi></msub></math></span>), characterized by a high increase of the ribbon thickness after passing the gap width, followed by a slower <span><math><mi>ER</mi></math></span> (<span><math><msub><mi>ER</mi><mi>B</mi></msub></math></span>). Sigma minus plot analysis showed that increasing <span><math><mi>RS</mi></math></span> led to an accelerated <span><math><msub><mi>ER</mi><mi>A</mi></msub></math></span> and <span><math><msub><mi>ER</mi><mi>B</mi></msub></math></span> which was related to the viscoelastic behaviour of <span><math><mi>MCC</mi></math></span>. The <span><math><mi>SCF</mi></math></span> only had an effect on the kinetics of <span><math><mi>ER</mi></math></span> if a brittle filler was added to the mixture. The conducted study established the first approach in literature to characterize the kinetics of <span><math><mi>ER</mi></math></span> in roll compaction. It supports the understanding and characterization of relaxation times and the effect of the <span><math><mi>RS</mi></math></span> and <span><math><mi>SCF</mi></math></span> in roll compaction.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100303"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701186","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":"Mechanistic insights of desmopressin loaded elastic liposomes for transdermal delivery: HSPiP predictive parameters and instrumental based evidences","authors":"Afzal Hussain ,&nbsp;Mohammad A. Altamimi ,&nbsp;Musaad A. Alshammari","doi":"10.1016/j.ijpx.2024.100304","DOIUrl":"10.1016/j.ijpx.2024.100304","url":null,"abstract":"<div><div>Desmopressin acetate (DA) is a first-line option for the treatment of hemophilia A, von Willebrand's disease, nocturnal enuresis, central diabetes insipidus, and various traumatic injuries. We extended previously reported desmopressin-loaded elastic liposomes (ODEL1) to investigate mechanistic insights into ODEL1 mediated augmented permeation across rat skin. HSPiP software and instrumental techniques such as differential scanning calorimeter (DSC), Fourier Transform infrared (FTIR), scanning electron microscopy (SEM), and fluorescent microscopy provided better understandings of permeation behavior. HSPiP was used to compare Hansen solubility parameter (HSP) of ODEL1, DA, components, and rat skins (control and treated) in terms of dispersion forces (δ_d), polar forces (δ_p), and hydrogen bonding (δ_h). FTIR, DSC, fluorescence microscopy, and SEM provided a detailed mechanistic understanding of the changes occurred after treatment. The values of δ_d, δ_p, and δ_H for DA were 20.6, 31.9, and 18.2 MPa^1/2, respectively, whereas these were 15.6, 14.97, and 2.4 MPa^1/2 for ODEL1, respectively, suggesting remarkable permeation of DA by changing innate cohesive energies of the skin. DA primarily interacts through δ_d and δ_p with the ODEL1 and the skin. Furthermore, the stretching and bending vibrations (molecular interactions) of the treated skins were quite diverse as compared to the untreated skin. ODEL1 caused a substantial thermal changes (shifted 67 to 65 °C, and 79 to 82.5 °C) for the surface protein and glycoprotein as compared to the untreated skin. Fluorescence and SEM confirmed relatively intense surface perturbation of the treated skin as compared to the control. Thus, ODEL1 was efficient in interacting with the skin surface for reversible changes and subsequently resulted in high permeation and drug deposition.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100304"},"PeriodicalIF":5.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701187","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":"Olive mill wastewater: From by-product to smart antioxidant material","authors":"Marco Ruggeri ,&nbsp;Fabrizio De Luca ,&nbsp;Amedeo Ungolo ,&nbsp;Barbara Vigani ,&nbsp;Alejandro J. Paredes ,&nbsp;Eleonora Russo ,&nbsp;Maria Grazia Bottone ,&nbsp;Eleonora Bianchi ,&nbsp;Franca Ferrari ,&nbsp;Silvia Rossi ,&nbsp;Giuseppina Sandri","doi":"10.1016/j.ijpx.2024.100301","DOIUrl":"10.1016/j.ijpx.2024.100301","url":null,"abstract":"<div><div>Olive mill wastewater (OMWW) is a byproduct of olive oil extraction that represents a critical environmental concern due to its potential adverse effects on ecosystems. Given these premises, spray-dried microparticles were designed and developed using maltodextrins as carriers to encapsulate OMWW bioactive compounds. The microparticles were manufactured using an easily scalable and sustainable spray-drying process. The resulting microparticles were smooth, spherical, and exhibited a mean particle size of about 18 μm. The systems demonstrated notable antioxidant properties with a DPPH radical scavenging activity higher than 60 %, due to the polyphenolic compounds of OMWW (about 24 g gallic acid equivalents per g of sample). In addition, the microparticles supported fibroblast and macrophage viability at concentrations up to 1 mg/mL. They also determined a 4-fold inflammation reduction in macrophages, improved collagen expression in fibroblasts, and modulated oxidative stress on aged fibroblasts. In conclusion, these microparticles could be considered as promising medical devices in wound healing, while offering a sustainable solution for valorizing OMWW.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100301"},"PeriodicalIF":5.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142701185","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":"Ultrasound-targeted sirolimus-loaded microbubbles improves acute rejection of heart transplantation in rats by inhibiting TGF-β1-Smad signaling pathway, promoting autophagy and reducing inflammation","authors":"Haiwei Bao,&nbsp;Lulu Dai,&nbsp;Huiyang Wang,&nbsp;Tianan Jiang","doi":"10.1016/j.ijpx.2024.100300","DOIUrl":"10.1016/j.ijpx.2024.100300","url":null,"abstract":"<div><div>Acute rejection (AR) remains a pivotal complication and leading cause of mortality within the first year following heart transplantation (HT). In this study, we assessed the impact of ultrasound-targeted microbubbles loaded with sirolimus (SIR-MBs) on AR in a rat HT model and delved into the underlying mechanisms. We established a rat abdominal ectopic HT model, which was stratified into three groups receiveing the PBS, SIR-MBs + ultrasound-targeted microbubble destruction (UTMD), and sirolimus, respectively. The protective effects of each treatments on survival rate, inflammatory response, autophagy and TGF-β1-Smad signaling pathway-related proteins were evaluted. Additionally, rescue experiment was performed <em>via</em> adding the autophagy inhibitor or TGF-β1 agonist in combination therapy. UTMD combined SIR-MBs mediated 15-fold higher local drug concentration compared to direct sirolimus administration. The infiltration of inflammatory cells in the transplanted hearts indicated that SIR-MBs combined with UTMD were effective in mitigating the inflammatory response, achieving levels significantly lower than those observed in the sirolimus group. Furthermore, after SIR-MBs combined with UTMD treatment, the expression levels of TGF-β1-Smad signaling pathway-related proteins in heart tissues also showed a significant decrease compared to the model control group. Conversely, the expressions of autophagy proteins LC3-II, Beclin-1 and β-arrestin showed an up-regulated trend. Rescue experiments also revealed that the enhancement in survival trends was markedly suppressed following the administration of CsA or SRI-011381, respectively. Collectively, our findings suggest that SIR-MBs combined with UTMD augment the local treatment efficacy for AR in rat HT models by inhibiting the TGF-β1-Smad signaling pathway, promoting autophagy, and alleviating inflammation.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100300"},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658488","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":"A hybrid system of mixture models for the prediction of particle size and shape, density, and flowability of pharmaceutical powder blends","authors":"Mohammad Salehian ,&nbsp;Jonathan Moores ,&nbsp;Jonathan Goldie ,&nbsp;Isra' Ibrahim ,&nbsp;Carlota Mendez Torrecillas ,&nbsp;Ishwari Wale ,&nbsp;Faisal Abbas ,&nbsp;Natalie Maclean ,&nbsp;John Robertson ,&nbsp;Alastair Florence ,&nbsp;Daniel Markl","doi":"10.1016/j.ijpx.2024.100298","DOIUrl":"10.1016/j.ijpx.2024.100298","url":null,"abstract":"<div><div>This paper presents a system of hybrid models that combine both mechanistic and data-driven approaches to predict physical powder blend properties from their raw component properties. Mechanistic, probabilistic models were developed to predict the particle size and shape, represented by aspect ratio, distributions of pharmaceutical blends using those of the raw components. Additionally, the accuracy of existing mixture rules for predicting the blend's true density and bulk density was assessed. Two data-driven models were developed to estimate the mixture's tapped density and flowability (represented by the flow function coefficient, FFC) using data from 86 mixtures, which utilized the principal components of predicted particle size and shape distributions in combination with the true density, and bulk density as input data, saving time and material by removing the need for resource-intensive shear testing for raw components. A model-based uncertainty quantification technique was designed to analyse the precision of model-predicted FFCs. The proposed particle size and shape mixture models outperformed the existing approach (weighted average of distribution percentiles) in terms of prediction accuracy while providing insights into the full distribution of the mixture. The presented hybrid system of models accurately predicts the mixture properties of different formulations and components with often <span><math><msup><mi>R</mi><mn>2</mn></msup><mo>&gt;</mo><mn>0.8</mn></math></span>, utilising raw material properties to reduce time and material resources on preparing and characterising blends.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100298"},"PeriodicalIF":5.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658961","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":"From design to 3D printing: A proof-of-concept study for multiple unit particle systems (MUPS) printed by dual extrusion fused filament fabrication","authors":"Lee Roy Oldfield ,&nbsp;Aaron Felix Christofer Mentrup ,&nbsp;Stefan Klinken-Uth ,&nbsp;Tobias Auel ,&nbsp;Anne Seidlitz","doi":"10.1016/j.ijpx.2024.100299","DOIUrl":"10.1016/j.ijpx.2024.100299","url":null,"abstract":"<div><div>MUPS (multiple unit particle systems) are oral dosage forms consisting of small particles which are filled into capsules or compressed into tablets. Compared to monolithic sustained-release tablets, MUPS tablets rapidly disintegrate inside the stomach releasing the contained small particles, which can be emptied from the stomach independent of housekeeping waves. Control of release can be achieved by adapting the particle composition. Despite the advantages of MUPS, only a limited number of preparations are available on the market. 3D printing could be a new advantageous method to produce MUPS tablets compared to the conventional production via tableting. Due to the increasing research interest in personalised medicine, especially regarding dose adjustments, this flexible production approach could be a promising concept. Therefore, this work proposes a concept for printing MUPS tablets using a dual extrusion fused filament fabrication 3D printer. The general idea is that the two print heads can be used independently to print a water-soluble tablet shell with the first print head and incorporate functional particles into the tablet shell with a second print head using different materials for each step. In this study, a modular four-particle-layered tablet computer model containing 196 cylindrical particles with a diameter of 1.4 mm, a height of 1.0 mm and a total tablet size of 22.6 × 8.5 × 6.0 mm is proposed. A first proof-of-concept study with drug-free commercially available polylactic acid filament for the particles and polyvinyl alcohol filament for the tablet shell revealed critical parameters (such as filament retraction, z-offset and water content of filaments) for the successful printing of the proposed computer model. In addition, the successfully printed model 3D-MUPS tablets and incorporated particles were characterised, revealing a reproducible manufacturing process. The printed model particles had a diameter of 1.27 ± 0.04 mm and a height of 1.05 ± 0.01 mm. One of the challenges of the new approach was to avoid particle agglomeration because of remelting processes during the printing with two print heads. 57.54 ± 18.59 % of the 196 printed particles were present as single particles. Finally, the transferability and suitability with a model API-loaded (paracetamol) hydroxypropyl methylcellulose filament for the particles and a polyvinyl alcohol tablet shell was successfully tested. On average, 80 % of paracetamol was released within 3 h (2–4 h). Overall, this work shows an innovative new manufacturing method for dose-adjustable personalised MUPS tablets but also considers new challenges arising from the different manufacturing processes.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100299"},"PeriodicalIF":5.2,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142571307","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":"Augmented glycerosomes as a promising approach against fungal ear infection: Optimization and microbiological, ex vivo and in vivo assessments","authors":"Sadek Ahmed ,&nbsp;Heba Attia ,&nbsp;Osama Saher ,&nbsp;Abdurrahman M. Fahmy","doi":"10.1016/j.ijpx.2024.100295","DOIUrl":"10.1016/j.ijpx.2024.100295","url":null,"abstract":"<div><div>In the current study, voriconazole (VCZ) augmented glycerosomes were optimized for topical otomycosis management according to a 2³ factorial design, employing a thin film hydration method. By optimizing Glycerol volume, limonene: VCZ ratio and Span® 60: soybean phosphatidyl choline (PC) ratio, glycerosomes with maximum percentage entrapment efficiency (%EE) and zeta potential (ZP) and minimum vesicle size (VS) and polydispersity index (PDI) were to be obtained. An optimal augmented glycerosomal formula (OAG) that contained 10 mg VCZ, 150 mg PC, and 3 mL glycerol, comprising 2.5: and 0.92:1 ratios of the latter two independent variables, was proposed via numerical optimization. OAG exhibited high %EE and ZP values and acceptable low values for VS and PDI (84.3 ± 2.0 %, −38.8 ± 1.8 mV, 191.0 ± 1.1 nm, and 0.192 ± 0.01, respectively). Extensive in <em>vitro</em> testing of OAG revealed the entrapment of VCZ within OAG, biphasic in <em>vitro</em> release profile, stability for up to 3 months at 2–8 °C and spherical morphology of OAG with VS like that obtained via zetasizer. OAG demonstrated higher permeated amounts of VCZ and flux values than VCZ suspension, leading to an enhancement ratio of 2.56 in the <em>ex vivo</em> permeation study. The deeper penetration ability of OAG demonstrated by Confocal Laser Scanning Microscopy and its superior in <em>vitro</em> antifungal activity confirmed the validity of the <em>ex vivo</em> study. Also, the histopathological study confirmed the safety of OAG for topical use, suggesting that VCZ OAG was a promising topical antimycotic formula.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100295"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534423","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":"Preservative-free electrospun nanofibrous inserts for sustained delivery of ceftazidime; design, characterization and pharmacokinetic investigation in rabbit's eye","authors":"Shiva Taghe ,&nbsp;Shahla Mirzaeei","doi":"10.1016/j.ijpx.2024.100297","DOIUrl":"10.1016/j.ijpx.2024.100297","url":null,"abstract":"<div><div>Ocular drug delivery presents significant challenges, attributed to the various anatomical and physiological barriers, as well as the limitations associated with conventional ocular formulations including low bioavailability, necessitating frequent dosing. The objective of the essay was to design sustained release nanofibrous inserts loaded with ceftazidime (CAZ), an antibiotic effective against gram-negative and gram-positive microorganisms, for the treatment of ocular infections. These nanofibers were fabricated using the electrospinning technique, employing biodegradable polymers such as polyvinyl alcohol (PVA), polycaprolactone (PCL) and Eudragit® (EUD). The nanofibrous inserts exhibited adequate mechanical strength for ocular use with an average diameter &lt; 250 nm. In the initial 12-h period, a burst drug release was observed, followed by a controlled release for 120 h. Cell viability test confirmed the non-toxicity and safety of the nanofibers. The <em>in vivo</em> study demonstrated that the inserts sustain a drug concentration exceeding the minimum inhibitory concentration (MIC) of <em>Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus</em> for 4 and 5 days, respectively. The AUC₀_–₁₂₀ for CAZ-PVA-PCL was reported 11,882.81 ± 80.5 μg·h/ml and for CAZ-PVA-EUD was 9649.39 ± 86.84 μg·h/ml. The nanofibrous inserts' extended drug release maintains effective antimicrobial concentrations, avoids the fluctuations of eye drops, and, by being preservative-free, eliminates cytotoxicity.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100297"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142658483","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}