Pub Date : 2024-10-09DOI: 10.1016/j.ijpharm.2024.124814
Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer’s disorder via preventing the aggregation of amyloid-beta-peptide-Aβ(1–42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer’s disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer’s-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aβ-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer’s disease medication.
{"title":"Dihydroquercetin nanoparticles nasal gel is a promising formulation for amelioration of Alzheimer’s disease","authors":"","doi":"10.1016/j.ijpharm.2024.124814","DOIUrl":"10.1016/j.ijpharm.2024.124814","url":null,"abstract":"<div><div>Dihydroquercetin is a natural flavonoid with anti-inflammatory, antioxidant, and neuroprotective activities. Dihydroquercetin exhibits a great neuroprotector promise in Alzheimer’s disorder via preventing the aggregation of amyloid-beta-peptide-Aβ(1–42). The goal of the study was to create dihydroquercetin-loaded-chitosan nanoparticles (DHQ-CS NPs) loaded to a mucoadhesive, thermosensitive in-situ gel for direct nasal administration to cure Alzheimer’s disorder. Loading drug in chitosan nanoparticles and incorporation into thermosensitive gel enhanced residence time and reduced mucociliary-clearance. Different in-vitro-physicochemical-characteristics of gels and nanoparticles-characterization were used to evaluate the formulations. The therapeutic effectiveness of DHQ-CS NPs gel was evaluated behaviorally, biochemically and histopathologically in Alzheimer’s-rat-model compared to intranasal DHQ gel. The small particles-size was obtained = 235.3 nm of DHQ-CS NPs. The DHQ-CS NPs gel demonstrated a greater release rate compared to the raw DHQ gel. Additionally, the nasal-administration of the DHQ-CS NPs gel showed better In-vivo results compared to DHQ gel, through improvement of memory and learning deficits and also the exploratory behavior and new object memory in streptozotocin induced-Alzheimer rats. Biochemically, the intranasal DHQ-CS NPs gel, showed reduced both Aβ-protein formation and tau protein hyperphosphorylation, inhibition of acetylcholine esterase activity and oxidative stress in the brain with increase of total antioxidants in the brain and serum, compared to DHQ gel. Histopathologically, the DHQ-CS NPs nasal gel produced improvement in the hippocampal and cerebral cortex structures, being comparable to the normal group. Consequently, the intranasal DHQ-CS NPs loaded in-situ gel seems to be a promising therapeutic formulation for Alzheimer’s disease medication.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390469","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}
Pub Date : 2024-10-09DOI: 10.1016/j.ijpharm.2024.124813
This study focuses on developing of a novel inhalation therapy for managing lung hyper-inflammation, producing hybrid polymer-lipid nanoparticles loaded with Iloprost (Ilo). These nanoparticles showed a size of approximately 100 nm with a core–shell structure and provided prolonged drug release, reaching 28 wt% after 6 h of incubation. The phospholipid composition and quantity (64 wt% on the total sample weight) result in minimal interaction with mucin and a significant effect on the rheology of a cystic fibrosis mucus model, in terms of reducing complex viscosity.
To obtain an inhalable microparticulate matrix suitable for incorporating Ilo@PEG-LPHNPs, the qualitative and quantitative composition of the feed fluid for the spray drying (SD) process was optimized. The selected composition (10 % wt/vol of mannitol and 10 % wt of ammonium bicarbonate relative to the weight of mannitol) was used to produce Nano-into Microparticles (NiM). The characterization of NiM revealed excellent aerodynamic properties, with a Mass Median Aerodynamic Diameter (MMAD) of 4.34 μm and a Fine Particle Fraction (FPF) of approximately 57 %. Biological characterization revealed that the particles are non-toxic to 16-HBE cells and can effectively evade macrophage uptake, likely due to the presence of PEG in their composition. Moreover, the delivered Iloprost significantly downregulates the production of the pro-inflammatory cytokine IL-6, showing the therapeutic potential of this drug delivery system.
{"title":"Exploiting inhalable microparticles incorporating hybrid polymer-lipid nanoparticles loaded with Iloprost manages lung hyper-inflammation","authors":"","doi":"10.1016/j.ijpharm.2024.124813","DOIUrl":"10.1016/j.ijpharm.2024.124813","url":null,"abstract":"<div><div>This study focuses on developing of a novel inhalation therapy for managing lung hyper-inflammation, producing hybrid polymer-lipid nanoparticles loaded with Iloprost (Ilo). These nanoparticles showed a size of approximately 100 nm with a core–shell structure and provided prolonged drug release, reaching 28 wt% after 6 h of incubation. The phospholipid composition and quantity (64 wt% on the total sample weight) result in minimal interaction with mucin and a significant effect on the rheology of a cystic fibrosis mucus model, in terms of reducing complex viscosity.</div><div>To obtain an inhalable microparticulate matrix suitable for incorporating Ilo@PEG-LPHNPs, the qualitative and quantitative composition of the feed fluid for the spray drying (SD) process was optimized. The selected composition (10 % wt/vol of mannitol and 10 % wt of ammonium bicarbonate relative to the weight of mannitol) was used to produce Nano-into Microparticles (NiM). The characterization of NiM revealed excellent aerodynamic properties, with a Mass Median Aerodynamic Diameter (MMAD) of 4.34 μm and a Fine Particle Fraction (FPF) of approximately 57 %. Biological characterization revealed that the particles are non-toxic to 16-HBE cells and can effectively evade macrophage uptake, likely due to the presence of PEG in their composition. Moreover, the delivered Iloprost significantly downregulates the production of the pro-inflammatory cytokine IL-6, showing the therapeutic potential of this drug delivery system.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390470","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}
Pub Date : 2024-10-09DOI: 10.1016/j.ijpharm.2024.124811
After organ transplantation, patients require treatment with immunosuppressive drugs to prevent immune rejection and transplantation failure. Tacrolimus (FK506) is a widely used immunosuppressant known for its potent immunosuppressive effect and narrow therapeutic range. Monitoring of FK506 blood concentrations is essential to avoid nephrotoxicity. In this study, a novel FK506 nanomedicine (FK506 cochleates) was developed using a microfluidic method to reduce variability among individuals and improve drug safety. The particle size of FK506 cochleates was (183.3 ± 1.4) nm, the zeta potential was −(39.28 ± 2.12) mV, and the encapsulation efficiency was more than 85 %. Particle size of FK506 cochleates could be maintained for up to 12 weeks in freeze-dried powder form. Small-angle X-ray scattering (SAXS) experiment confirmed the formation of cochleates by adding calcium solution. In vitro release studies demonstrated a sustained-release profile of FK506 from the cochleates carrier. Furthermore, the cochleates carrier could protect FK506 from the influence of stomach acid and slowly release the drug in the intestine. After oral administration, FK506 cochleates exhibited sustained-release properties in rats, accumulating in the spleen and lymph nodes − key anatomical sites for FK506’s pharmacological action. Importantly, FK506 cochleates significantly prolonged the survival time in the rabbit heart transplantation model while maintaining good safety profiles. In conclusion, the FK506 cochleates showed promising potential for enhancing drug safety in therapeutic organ transplantation.
{"title":"Preparation and evaluation of novel oral tacrolimus nanocochleates for organ transplantation to reduce individual differences and improve drug safety","authors":"","doi":"10.1016/j.ijpharm.2024.124811","DOIUrl":"10.1016/j.ijpharm.2024.124811","url":null,"abstract":"<div><div>After organ transplantation, patients require treatment with immunosuppressive drugs to prevent immune rejection and transplantation failure. Tacrolimus (FK506) is a widely used immunosuppressant known for its potent immunosuppressive effect and narrow therapeutic range. Monitoring of FK506 blood concentrations is essential to avoid nephrotoxicity. In this study, a novel FK506 nanomedicine (FK506 cochleates) was developed using a microfluidic method to reduce variability among individuals and improve drug safety. The particle size of FK506 cochleates was (183.3 ± 1.4) nm, the zeta potential was −(39.28 ± 2.12) mV, and the encapsulation efficiency was more than 85 %. Particle size of FK506 cochleates could be maintained for up to 12 weeks in freeze-dried powder form. Small-angle X-ray scattering (SAXS) experiment confirmed the formation of cochleates by adding calcium solution. <em>In vitro</em> release studies demonstrated a sustained-release profile of FK506 from the cochleates carrier. Furthermore, the cochleates carrier could protect FK506 from the influence of stomach acid and slowly release the drug in the intestine. After oral administration, FK506 cochleates exhibited sustained-release properties in rats, accumulating in the spleen and lymph nodes − key anatomical sites for FK506’s pharmacological action. Importantly, FK506 cochleates significantly prolonged the survival time in the rabbit heart transplantation model while maintaining good safety profiles. In conclusion, the FK506 cochleates showed promising potential for enhancing drug safety in therapeutic organ transplantation.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390485","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}
Pub Date : 2024-10-09DOI: 10.1016/j.ijpharm.2024.124816
{"title":"Dr. Paul W. S. Heng, a guru in pharmaceutical processing research","authors":"","doi":"10.1016/j.ijpharm.2024.124816","DOIUrl":"10.1016/j.ijpharm.2024.124816","url":null,"abstract":"","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400235","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}
Pub Date : 2024-10-07DOI: 10.1016/j.ijpharm.2024.124809
Hennie Marie Johnsen, Werner Filtvedt, Jo Klaveness, Marianne Hiorth
Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within pores, improving dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious Si wafer material synthesis, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF), and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.
{"title":"Nano-strategies for advancing oral drug delivery: Porous silicon particles and cyclodextrin encapsulation for enhanced dissolution of poorly soluble drugs.","authors":"Hennie Marie Johnsen, Werner Filtvedt, Jo Klaveness, Marianne Hiorth","doi":"10.1016/j.ijpharm.2024.124809","DOIUrl":"https://doi.org/10.1016/j.ijpharm.2024.124809","url":null,"abstract":"<p><p>Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within pores, improving dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious Si wafer material synthesis, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF), and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.</p>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390472","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}
Pub Date : 2024-10-06DOI: 10.1016/j.ijpharm.2024.124786
Neurodegenerative diseases (ND) are often accompanied by dementia, motor dysfunction, or disability. Caring for these patients imposes a significant psychological and financial burden on families. Until now, there are no effective methods for the treatment of NDs. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common. Recently, studies have revealed that the overexpression of certain genes may be linked to the occurrence of AD and PD. Small interfering RNAs (siRNAs) are a powerful tool for gene silencing because they can specifically bind to and cleave target mRNA. However, the intrinsic properties of naked siRNA and various physiological barriers limit the application of siRNA in the brain. Nanotechnology is a promising option for addressing these issues. Nanoparticles are not only able to protect siRNA from degradation but also have the advantage of crossing various physiological barriers to reach the brain target of siRNA. In this review, we aim to introduce diverse nanotechnology used for delivering siRNA to treat AD and PD. Finally, we will briefly discuss our perspectives on this promising field.
{"title":"Nanotechnology used for siRNA delivery for the treatment of neurodegenerative diseases: Focusing on Alzheimer’s disease and Parkinson’s disease","authors":"","doi":"10.1016/j.ijpharm.2024.124786","DOIUrl":"10.1016/j.ijpharm.2024.124786","url":null,"abstract":"<div><div>Neurodegenerative diseases (ND) are often accompanied by dementia, motor dysfunction, or disability. Caring for these patients imposes a significant psychological and financial burden on families. Until now, there are no effective methods for the treatment of NDs. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common. Recently, studies have revealed that the overexpression of certain genes may be linked to the occurrence of AD and PD. Small interfering RNAs (siRNAs) are a powerful tool for gene silencing because they can specifically bind to and cleave target mRNA. However, the intrinsic properties of naked siRNA and various physiological barriers limit the application of siRNA in the brain. Nanotechnology is a promising option for addressing these issues. Nanoparticles are not only able to protect siRNA from degradation but also have the advantage of crossing various physiological barriers to reach the brain target of siRNA. In this review, we aim to introduce diverse nanotechnology used for delivering siRNA to treat AD and PD. Finally, we will briefly discuss our perspectives on this promising field.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390484","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}
Pub Date : 2024-10-06DOI: 10.1016/j.ijpharm.2024.124808
In-line monitoring of critical quality attributes (CQAs) during a tableting process is an essential step toward a real-time release strategy. Such CQAs can be the tablet mass, the API content, dissolution, hardness and tensile strength. Since dissolution testing is laborious and time-consuming and cannot be performed in-line, it is desirable to replace dissolution testing with predictive models based on other CQAs that affect the dissolution characteristics, such as the tablet porosity and hardness. Traditionally, porosity is determined offline via gas adsorption methods or other techniques, such as Terahertz spectroscopy or gas in scattering media absorption spectroscopy. Tablet hardness is typically established using a hardness tester. While these destructive tests can readily be performed at-line, they have limited applicability in in-line settings for a high-percentage inspection. Optical coherence tomography (OCT) has recently been proposed as a possible tool for determining quality attributes. This work describes the first application of OCT for the prediction of tablet porosity and hardness. OCT measurements of tablets produced in a ConsiGma 25™ tableting line and a Stylcam 200R compaction simulator in several compaction force settings were performed and correlated with the porosity and hardness. It was demonstrated that OCT can easily be installed in-line and provide real-time information about critical material attributes. These insights confirm the applicability of OCT as a real-time quality control tool and its potential to replace time-consuming and destructive offline measurements.
在压片过程中对关键质量属性（CQA）进行在线监测是实现实时释放策略的重要一步。此类 CQA 包括片剂质量、原料药含量、溶出度、硬度和拉伸强度。由于溶出度测试费时费力，而且无法在线进行，因此最好用基于其他影响溶出度特性的 CQA（如片剂孔隙率和硬度）的预测模型来取代溶出度测试。传统上，孔隙率是通过气体吸附法或其他技术（如太赫兹光谱法或气体在散射介质中的吸收光谱法）离线确定的。片剂硬度通常使用硬度计来确定。虽然这些破坏性测试可以在生产线上进行，但它们在生产线上进行高比例检测的适用性有限。光学相干断层扫描（OCT）最近被提议作为确定质量属性的一种可能工具。这项工作描述了 OCT 在预测片剂孔隙率和硬度方面的首次应用。对在 ConsiGma 25™ 压片生产线和 Stylcam 200R 压实模拟器上生产的片剂在几种压实力设置下进行了 OCT 测量，并将其与孔隙率和硬度相关联。结果表明，OCT 可以轻松在线安装，并提供有关关键材料属性的实时信息。这些研究结果证实了 OCT 作为实时质量控制工具的适用性，以及取代耗时且具有破坏性的离线测量的潜力。
{"title":"In-line porosity and hardness monitoring of tablets by means of optical coherence tomography","authors":"","doi":"10.1016/j.ijpharm.2024.124808","DOIUrl":"10.1016/j.ijpharm.2024.124808","url":null,"abstract":"<div><div>In-line monitoring of critical quality attributes (CQAs) during a tableting process is an essential step toward a real-time release strategy. Such CQAs can be the tablet mass, the API content, dissolution, hardness and tensile strength. Since dissolution testing is laborious and time-consuming and cannot be performed in-line, it is desirable to replace dissolution testing with predictive models based on other CQAs that affect the dissolution characteristics, such as the tablet porosity and hardness. Traditionally, porosity is determined offline via gas adsorption methods or other techniques, such as Terahertz spectroscopy or gas in scattering media absorption spectroscopy. Tablet hardness is typically established using a hardness tester. While these destructive tests can readily be performed at-line, they have limited applicability in in-line settings for a high-percentage inspection. Optical coherence tomography (OCT) has recently been proposed as a possible tool for determining quality attributes. This work describes the first application of OCT for the prediction of tablet porosity and hardness. OCT measurements of tablets produced in a ConsiGma 25™ tableting line and a Stylcam 200R compaction simulator in several compaction force settings were performed and correlated with the porosity and hardness. It was demonstrated that OCT can easily be installed in-line and provide real-time information about critical material attributes. These insights confirm the applicability of OCT as a real-time quality control tool and its potential to replace time-consuming and destructive offline measurements.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390471","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}
Pub Date : 2024-10-05DOI: 10.1016/j.ijpharm.2024.124777
Highly viscous drugs cannot be delivered through a needle. Typically, this means that these drugs are formulated at lower concentrations, demanding higher delivery volumes, which often must be delivered intravenously. Jet injection may provide an important solution for viscous drug delivery. Jet injection is a needle-free drug delivery technique whereby a liquid drug is formed into a hair-thin (∼200 µm) high-speed (>100 m/s) jet that penetrates and delivers itself into tissue. While it may seem that it would be just as difficult to form a viscous drug into a high-speed jet as it is to force it down a needle, this is not the case. Recent work has revealed that ‘viscous-heating’ during jet injection can result in significant temperature increase, and resultant viscosity decrease, in a thin outer-layer of the jet; this phenomenon effectively results in the drug ‘self-lubricating’ as it passes through a jet injection orifice. Despite the potential for this finding to revolutionise the subcutaneous delivery of high-viscosity drugs, little further work in this area has since been reported on. In this work we develop finite element models of needle-free injection to investigate how viscous heating affects jet production, how heat exchange with the orifice material influences this process, and to what extent jet production is affected by the initial temperature of the fluid. We then conduct novel high-speed measurements of jet and orifice temperature changes due to viscous heating. We find that viscous heating is responsible for approximately doubling the speed of jets that can be produced with very viscous fluid (1 Pa·s) at room temperature. The thermal conductivity of the orifice can transfer heat away from the perimeter of the jet, and thus reduce the lubricating effect of viscous heating. We then show that by preheating 99 % glycerol (1 Pa·s) from 7 °C to 37 °C the jet speed can be increased 6-fold. We also demonstrate the successful delivery of a very viscous glycerol solution using preheated jet injection into ex vivo porcine tissue. Given that 99 % glycerol is 10- to 100-fold more viscous than current protein therapeutics, our findings demonstrate the potential for jet injection, with or without additional drug preheating, to deliver drug formulations, needle-free, that are much more viscous than those currently delivered through needles.
{"title":"The effect of temperature-dependent drug viscosity on needle-free jet injection","authors":"","doi":"10.1016/j.ijpharm.2024.124777","DOIUrl":"10.1016/j.ijpharm.2024.124777","url":null,"abstract":"<div><div>Highly viscous drugs cannot be delivered through a needle. Typically, this means that these drugs are formulated at lower concentrations, demanding higher delivery volumes, which often must be delivered intravenously. Jet injection may provide an important solution for viscous drug delivery. Jet injection is a needle-free drug delivery technique whereby a liquid drug is formed into a hair-thin (∼200 µm) high-speed (>100 m/s) jet that penetrates and delivers itself into tissue. While it may seem that it would be just as difficult to form a viscous drug into a high-speed jet as it is to force it down a needle, this is not the case. Recent work has revealed that ‘viscous-heating’ during jet injection can result in significant temperature increase, and resultant viscosity decrease, in a thin outer-layer of the jet; this phenomenon effectively results in the drug ‘self-lubricating’ as it passes through a jet injection orifice. Despite the potential for this finding to revolutionise the subcutaneous delivery of high-viscosity drugs, little further work in this area has since been reported on. In this work we develop finite element models of needle-free injection to investigate how viscous heating affects jet production, how heat exchange with the orifice material influences this process, and to what extent jet production is affected by the initial temperature of the fluid. We then conduct novel high-speed measurements of jet and orifice temperature changes due to viscous heating. We find that viscous heating is responsible for approximately doubling the speed of jets that can be produced with very viscous fluid (1 Pa·s) at room temperature. The thermal conductivity of the orifice can transfer heat away from the perimeter of the jet, and thus reduce the lubricating effect of viscous heating. We then show that by preheating 99 % glycerol (1 Pa·s) from 7 °C to 37 °C the jet speed can be increased 6-fold. We also demonstrate the successful delivery of a very viscous glycerol solution using preheated jet injection into ex vivo porcine tissue. Given that 99 % glycerol is 10- to 100-fold more viscous than current protein therapeutics, our findings demonstrate the potential for jet injection, with or without additional drug preheating, to deliver drug formulations, needle-free, that are much more viscous than those currently delivered through needles.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380829","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}
Pub Date : 2024-10-05DOI: 10.1016/j.ijpharm.2024.124799
Nanotechnology has brought about a significant revolution in drug delivery, and research in this domain is increasingly focusing on understanding the role of nanoparticle (NP) characteristics in drug delivery efficiency. First and foremost, we center our attention on the size of nanoparticles. Studies have indicated that NP size significantly influences factors such as circulation time, targeting capabilities, and cellular uptake. Secondly, we examine the significance of nanoparticle shape. Various studies suggest that NPs of different shapes affect cellular uptake mechanisms and offer potential advantages in directing drug delivery. For instance, cylindrical or needle-like NPs may facilitate better cellular uptake compared to spherical NPs. Lastly, we address the importance of nanoparticle charge. Zeta potential can impact the targeting and cellular uptake of NPs. Positively charged NPs may be better absorbed by negatively charged cells, whereas negatively charged NPs might perform more effectively in positively charged cells. This review provides essential insights into understanding the role of nanoparticles in drug delivery. The properties of nanoparticles, including size, shape, and charge, should be taken into consideration in the rational design of drug delivery systems, as optimizing these characteristics can contribute to more efficient targeting of drugs to the desired tissues. Thus, research into nanoparticle properties will continue to play a crucial role in the future of drug delivery.
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Pub Date : 2024-10-05DOI: 10.1016/j.ijpharm.2024.124800
The evolution of sophisticated nanosystems has revolutionized biomedicine, notably in treating neurodegenerative diseases and cancer. These systems show potential in delivering medication precisely to affected tissues, improving treatment effectiveness while minimizing side effects. Nevertheless, a major hurdle in targeted drug delivery is breaching the blood–brain barrier (BBB), a selective shield separating the bloodstream from the brain and spinal cord. The tight junctions between endothelial cells in brain capillaries create a formidable physical barrier, alongside efflux transporters that expel harmful molecules. This presents a notable challenge for brain drug delivery. Nanosystems present distinct advantages in overcoming BBB challenges, offering enhanced drug efficacy, reduced side effects, improved stability, and controlled release. Despite their promise, challenges persist, such as the BBB’s regional variability hindering uniform drug distribution. Efflux transporters can also limit therapeutic agent efficacy, while nanosystem toxicity necessitates rigorous safety evaluations. Understanding the long-term impact of nanomaterials on the brain remains crucial. Additionally, addressing nanosystem scalability, cost-effectiveness, and safety profiles is vital for widespread clinical implementation. This review delves into the advancements and obstacles of advanced nanosystems in targeted drug delivery for neurodegenerative diseases and cancer therapy, with a focus on overcoming the BBB.
{"title":"Nanosystems for targeted drug Delivery: Innovations and challenges in overcoming the Blood-Brain barrier for neurodegenerative disease and cancer therapy","authors":"","doi":"10.1016/j.ijpharm.2024.124800","DOIUrl":"10.1016/j.ijpharm.2024.124800","url":null,"abstract":"<div><div>The evolution of sophisticated nanosystems has revolutionized biomedicine, notably in treating neurodegenerative diseases and cancer. These systems show potential in delivering medication precisely to affected tissues, improving treatment effectiveness while minimizing side effects. Nevertheless, a major hurdle in targeted drug delivery is breaching the blood–brain barrier (BBB), a selective shield separating the bloodstream from the brain and spinal cord. The tight junctions between endothelial cells in brain capillaries create a formidable physical barrier, alongside efflux transporters that expel harmful molecules. This presents a notable challenge for brain drug delivery. Nanosystems present distinct advantages in overcoming BBB challenges, offering enhanced drug efficacy, reduced side effects, improved stability, and controlled release. Despite their promise, challenges persist, such as the BBB’s regional variability hindering uniform drug distribution. Efflux transporters can also limit therapeutic agent efficacy, while nanosystem toxicity necessitates rigorous safety evaluations. Understanding the long-term impact of nanomaterials on the brain remains crucial. Additionally, addressing nanosystem scalability, cost-effectiveness, and safety profiles is vital for widespread clinical implementation. This review delves into the advancements and obstacles of advanced nanosystems in targeted drug delivery for neurodegenerative diseases and cancer therapy, with a focus on overcoming the BBB.</div></div>","PeriodicalId":14187,"journal":{"name":"International Journal of Pharmaceutics","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390483","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}
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