International Journal of Pharmaceutics: X最新文献

{"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}

{"title":"Design of an innovative nanovehicle to enhance brain permeability of a novel 5-HT6 receptor antagonist","authors":"María Javiera Alvarez-Figueroa ,&nbsp;Francisco Nuñez-Navarro ,&nbsp;Gonzalo Recabarren-Gajardo ,&nbsp;José Vicente González-Aramundiz","doi":"10.1016/j.ijpx.2024.100296","DOIUrl":"10.1016/j.ijpx.2024.100296","url":null,"abstract":"<div><div>An innovative nanovehicle based on lipid nanocapsules (LNC) was designed to facilitate the passage of a new 5-HT₆ receptor antagonist, namely PUC-10, through the blood-brain barrier. PUC-10 is a new synthetic <em>N</em>-arylsulfonylindole that has demonstrated potent 5-HT₆ receptor antagonist activity, but it exhibits poor solubility in water, which indicates limited absorption. The lipid nanocapsules designed had a nanometric size (53 nm), a monomodal distribution (PI&lt;0.2), a negative Z potential (−17 ± 7 mV) and allowed efficient PUC-10 encapsulation (74 %). Furthermore, the LNC demonstrated to be stable for at least 4 weeks at 4 °C (storage conditions), for at least 4 h in DMEM at pH 7.4, and for 18 h in water with 5 % DMSO, with both latter conditions maintained at 37 °C. They also demonstrated that cell viability was not affected at the different concentrations studied. Finally, <em>in vitro</em> studies that simulate the blood brain barrier (PAMPA-BBB) demonstrated that the nanoencapsulation of PUC-10 promoted their penetration through the blood-brain barrier, with a calculated permeability of 1.3 × 10⁻⁸ cm/s, compared to the null permeability exhibited by non-nanoencapsulated PUC-10.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100296"},"PeriodicalIF":5.2,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142551881","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":"Development of cancer-associated fibroblasts-targeting polymeric nanoparticles loaded with 8-O-methylfusarubin for breast cancer treatment","authors":"Kamonlatth Rodponthukwaji ,&nbsp;Suyanee Thongchot ,&nbsp;Suttikiat Deureh ,&nbsp;Tanva Thongkleang ,&nbsp;Mattika Thaweesuvannasak ,&nbsp;Kornrawee Srichan ,&nbsp;Chatchawan Srisawat ,&nbsp;Peti Thuwajit ,&nbsp;Kytai T. Nguyen ,&nbsp;Kwanruthai Tadpetch ,&nbsp;Chanitra Thuwajit ,&nbsp;Primana Punnakitikashem","doi":"10.1016/j.ijpx.2024.100294","DOIUrl":"10.1016/j.ijpx.2024.100294","url":null,"abstract":"<div><div>Cancer-associated fibroblasts (CAFs) are abundant stromal cells residing in a tumor microenvironment (TME) which are associated with the progression of tumor. Herein, we developed novel CAFs-targeting polymeric nanoparticles encapsulating a synthetic 8-<em>O</em>-methylfusarubin (OMF) compound (OMF@NPs-anti-FAP). Anti-FAP/fibroblast activation protein antibody was employed as a CAFs-targeting ligand. The physicochemical properties of the synthesized nanomaterials were firstly investigated with various techniques. The cytocompatibility of polymeric nanoparticles (NPs) was elicited through cell viability of CAFs and human breast epithelial cells, MCF-10A. Additionally, the anti-FAP-conjugated NPs displayed different degrees of cellular internalization regarding the FAP expression level on the CAFs' surface. However, CAFs exposed to NPs containing OMF demonstrated significant cell death which were associated with the apoptotic pathway as confirmed by caspase-3/7 activity. Upon OMF@NPs-anti-FAP treatment, an enhanced toxicity was clearly observed in 3D spheroid models. High FAP-expressed PC-B-132CAFs demonstrated a high percentage of cell death compared to other cells with a low level of FAP expression analyzed by flow cytometry (e.g. MCF-10A, HDFa, and PC-B-142CAFs). This result emphasized the importance of anti-FAP antibody as a targeting ligand. These findings suggest that the fabricated nanosystem of OMF-loaded polymeric NPs with CAFs' high specificity holds a potential NP-based platform for improvement in breast cancer treatment.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100294"},"PeriodicalIF":5.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534422","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 wound dressing porosity and exudate viscosity on the exudate absorption: In vitro and in silico tests with 3D printed hydrogels","authors":"Alejandro Seijo-Rabina ,&nbsp;Santiago Paramés-Estevez ,&nbsp;Angel Concheiro ,&nbsp;Alberto Pérez-Muñuzuri ,&nbsp;Carmen Alvarez-Lorenzo","doi":"10.1016/j.ijpx.2024.100288","DOIUrl":"10.1016/j.ijpx.2024.100288","url":null,"abstract":"<div><div>Exudate absorption is a key parameter for proper wound dressing performance. Unlike standardized tests that consider exudate viscosity close to that of water, patients' exudates vary greatly in composition and, therefore, viscosity. This work aimed to investigate the effects of exudate viscosity and pore size of hydrogel-like dressings on the exudate absorption rate to establish rational criteria for the design of dressings that can meet the personalized needs of wound treatment. Computer-aided design (CAD) was used for Digital Light Processing (DLP) 3D printing of hydrogels with 0%, 30% and 60% porosity. The hydrogels were characterized in detail, and the absorption of two simulated exudate fluids (SEFs) was video-recorded. The same CAD files were used to develop <em>in silico</em> models to simulate exudate uptake rate. Both <em>in vitro</em> data and <em>in silico</em> modeling revealed that low-viscosity SEF penetrates faster through relatively small hydrogel pores (approx. 400 μm) compared to larger pores (approx. 1100 μm) due to capillary forces. However, <em>in vitro</em> vertical uptake took longer than when simulated using CAD design due to lateral fluid absorption through the pore walls in the hydrogel bulk. Distortions of hydrogel channels (micro-CT images) and lateral fluid absorption should be both considered for <em>in silico</em> simulation of SEF penetration. Overall, the results evidenced that porous hydrogel dressings allow rapid penetration (within a few seconds) and hosting of exudates, especially for pore size &lt;1 mm. This information may be useful for design criteria of wound dressings with adequate fluid handling and drug release rate.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100288"},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142444682","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":"Ocular mucoadhesive and biodegradable spanlastics loaded cationic spongy insert for enhancing and sustaining the anti-inflammatory effect of prednisolone Na phosphate; Preparation, I-optimal optimization, and In-vivo evaluation","authors":"Mayada Said ,&nbsp;Khaled M. Ali ,&nbsp;Munerah M. Alfadhel ,&nbsp;Obaid Afzal ,&nbsp;Basmah Nasser Aldosari ,&nbsp;Maha Alsunbul ,&nbsp;Rawan Bafail ,&nbsp;Randa Mohammed Zaki","doi":"10.1016/j.ijpx.2024.100293","DOIUrl":"10.1016/j.ijpx.2024.100293","url":null,"abstract":"<div><div>This study aimed to formulate and statistically optimize spanlastics loaded spongy insert (SPLs-SI) of prednisolone Na phosphate (PRED) to enhance and sustain its anti-inflammatory effect in a controlled manner. An I-optimal optimization was employed using Design-Expert® software. The formulation variables were sonication time, the Span 60: EA ratio and type of edge activator (Tween 80 or PVA) while Entrapment efficiency (EE%), Vesicles' size (VS) and Zeta potential (ZP) were set as the dependent responses. This resulted in an optimum spanlastics (SPLs) formulation with a desirability of 0.919. It had a Span60:Tween80 ratio of 6:1 with a sonication time of 9.5 min. It was evaluated in terms of its EE%, VS, ZP, release behavior in comparison to drug solution in addition to the effect of aging on its characteristics. It had EE% of 87.56, VS of 152.2 nm and ZP of −37.38 Mv. It showed sustained release behavior of PRED in comparison to drug solution with good stability for thirty days. TEM images of the optimized PRED SPLs formulation showed spherical non-aggregated nanovesicles. Then it was loaded into chitosan spongy insert and evaluated in terms of its visual appearance, pH and mucoadhesion properties. It showed good mucoadhesive properties and pH in the safe ocular region. The FTIR, DSC and XRD spectra showed that PRED was successfully entrapped inside the SPLs vesicles. It was then exposed to an in-vivo studies where it was capable of enhancing the anti-inflammatory effect of PRED in a sustained manner with once daily application compared to commercial PRED solution. The spongy insert has the potential to be a promising carrier for the ocular delivery of PRED.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100293"},"PeriodicalIF":5.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534420","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":"Multifunctional poloxamer-based thermo-responsive hydrogel loaded with human lactoferricin niosomes: In vitro study on anti-bacterial activity, accelerate wound healing, and anti-inflammation","authors":"Sirikwan Sangboonruang ,&nbsp;Natthawat Semakul ,&nbsp;Kiattikhun Manokruang ,&nbsp;Nuttawut Khammata ,&nbsp;Kanyaluck Jantakee ,&nbsp;Katanchalee Mai-Ngam ,&nbsp;Satrawut Charoenla ,&nbsp;Phadungkiat Khamnoi ,&nbsp;Kanokwan Saengsawang ,&nbsp;Usanee Wattananandkul ,&nbsp;Sorasak Intorasoot ,&nbsp;Khajornsak Tragoolpua","doi":"10.1016/j.ijpx.2024.100291","DOIUrl":"10.1016/j.ijpx.2024.100291","url":null,"abstract":"<div><div>Chronic wound infections are attributed to delayed tissue repair, which remains a major clinical challenge in long-term health care. Particularly, infections with antibiotic resistance have more serious effects on health, often resulting in unsuccessful treatments. Thus, antimicrobial peptide (AMP)-based therapy holds promise as a potential therapeutic approach to overcoming drug resistance. Conventional wound dressing is a passive strategy for wound care that is not capable of eradicating pathogens and promoting tissue repair. In this study, we aim to construct an advanced wound dressing; a thermo-responsive hydrogel incorporated with lactoferricin (Lfcin) niosome (Lfcin-Nio/hydrogel) for bacterial pathogen treatment. The Lfcin-loaded niosome (Lfcin-Nio) has a particle size of 396.91 ± 20.96 nm, 0.38 ± 0.01 of PdI, −10.5 ± 0.3 mV of ζ potential, and 72.30 ± 7.05 % Lfcin entrapment efficiency. Lfcin-Nio exhibited broad antibacterial activity on both drug-susceptible and drug-resistant strains, and also on bacteria residing in the biofilm matrix. The Lfcin-Nio/hydrogel was fabricated from 0.5 % <em>w</em>/<em>v</em> poloxamer 188–20 % w/v poloxamer 407, and supplemented with Lfcin-Nio and epidermal growth factor (EGF). The physical properties of Lfcin-Nio/hydrogels showed elasticity, swelling ability, and strong injectability with responsiveness to 33–37 °C temperatures. The biological properties of Lfcin-Nio/hydrogels exhibited a bactericidal effect against drug-resistant strains of <em>S. aureus</em> and <em>P. aeruginosa,</em> and showed less toxicity to the human skin fibroblast. It also promoted the healing of scratches by 55 % within 6 h, compared to the wound closure rate of 20 % in the cell control. The inflammatory response of the Lfcin-Nio/hydrogel-treated cells was reduced <em>via</em> suppression of <em>IL-1β</em> and <em>COX-2</em> mRNA expressions. From this study, Lfcin-Nio/hydrogels can be suggested as a modern wound dressing that possesses multifunctional and beneficial properties for the management of chronic wound infections.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100291"},"PeriodicalIF":5.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441265","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":"Study on the preparation of stabilizer-free silymarin nanocrystals and its oral absorption mechanisms","authors":"Liangxing Tu ,&nbsp;Ping Han ,&nbsp;Yongbing Sun ,&nbsp;Yi Jin ,&nbsp;Kaili Hu ,&nbsp;Meng Cheng ,&nbsp;Yisen Shao ,&nbsp;Jianfang Feng ,&nbsp;Fangying Yuan","doi":"10.1016/j.ijpx.2024.100292","DOIUrl":"10.1016/j.ijpx.2024.100292","url":null,"abstract":"<div><div>Many researchers have studied the oral absorption mechanisms yet, however, considering stabilizers often participate in the absorption process of nanocrystals, these known mechanisms may be incorrect. Hence in this study, we aimed to explore the correct absorption mechanism of nanocrystals by performing related studies on stabilizer-free nanocrystals. We firstly prepared stabilizer-free silymarin nanocrystals by high-pressure homogenization, and then performed absorption-related studies, such as solubility, dissolution rate, pharmacokinetic study, cellular uptake and intracellular transport. Results showed the stabilizer-free silymarin nanocrystals had an average particle size of (450.2 ± 4.46) nm, with PDI of 0.280 ± 0.021 and Zeta potential of −26.9 ± 2.4 mV. The conversion of silymarin crude drug to stabilizer-free silymarin nanocrystals increased the compound's solubility by 1.41 times, with a dissolution rate of 92.2 % in water within 30 min compared to 38.5 % for crude drugs. Pharmacokinetic studies showed the oral bioavailability of stabilizer-free silymarin nanocrystals was found to be 1.48 times greater than that of the crude drugs. The cell experimentation results demonstrated that the stabilizer-silymarin nanocrystals can improve uptake but have poor transmembrane transport properties. Most researchers believe that nanocrystals can enhance transmembrane transport of drugs via an endocytosis-mediated pathway. In fact, nanocrystals are indeed endocytosed more by the cells, but this transport pathway is poor because the cells lack the intracellular transport pathway to transport nanocrystals from the AP side to the BP side. Therefore, we believe that the intracellular transport of nanocrystals can be enhanced by modifications and other carriers if needed to improve nanocrystals' ability to promote oral absorption.</div></div>","PeriodicalId":14280,"journal":{"name":"International Journal of Pharmaceutics: X","volume":"8 ","pages":"Article 100292"},"PeriodicalIF":5.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534421","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}