Drug Delivery and Translational Research最新文献

筛选
英文 中文
Zolmitriptan niosomal transdermal patches: combating migraine via epigenetic and endocannabinoid pathways and reversal of migraine hypercoagulability. 佐米曲普坦纳米透皮贴片:通过表观遗传学和内源性大麻素途径防治偏头痛并逆转偏头痛的高凝状态。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-05 DOI: 10.1007/s13346-024-01731-6
Nancy Abdel Hamid Abou Youssef, Gihan Salah Labib, Abeer Ahmed Kassem, Nesrine S El-Mezayen
{"title":"Zolmitriptan niosomal transdermal patches: combating migraine via epigenetic and endocannabinoid pathways and reversal of migraine hypercoagulability.","authors":"Nancy Abdel Hamid Abou Youssef, Gihan Salah Labib, Abeer Ahmed Kassem, Nesrine S El-Mezayen","doi":"10.1007/s13346-024-01731-6","DOIUrl":"https://doi.org/10.1007/s13346-024-01731-6","url":null,"abstract":"<p><p>Conventional zolmitriptan (ZOL) has limited oral bioavailability, many adverse effects, and poor membrane penetrability that negatively influences its accessibility to its 5-HT<sub>1B/1D</sub> receptor binding pocket, located transmemberanous. This work aimed at preparing transdermal ZOL-nanoformulation (niosomes) to surpass these limitations and to explore novel antimigraine mechanisms for ZOL via modulation of the epigenetically-altered chronification genes (RAMP-1, NPTX-2) or microRNAs and affecting the endocannabinoid CB-1/MAPK pathway. The prepared ZOL niosomes (F<sub>sp60/6-1:1</sub>) exhibited %EE of 57.28%, PS of 472.3 nm, PDI of 0.366, and ZP of -26 mV were cast into patch with content uniformity of 93.12%, maintained endurance after 200-times folding, no interaction between its components (FT-IR), a biphasic release pattern and good stability after storage at 4 °C for 6 months. In-vivo ZOL-patch application in rats with nitroglycerin-induced migraine showed significant management of migraine pain symptoms and photophobia assessed behaviorally, decreased brain levels of the trigeminal neuronal activation marker (c-fos), the migraine pain neurotransmitter (CGRP) and the serum levels of different migraine pain markers (substance P, nitric-oxide, and TNF-α). It also significantly decreased RAMP-1, NPTX-2, miR-382-5p, and CB-1/MAPK gene expression reflecting improved efficacy and brain receptors delivery to a much greater extent than conventional ZOL has done. Additionally, this nanoformulation significantly opposed migraine-induced platelet activation and hypercoagulable status in both central and peripheral circulations as evidenced by the significant decrease in adenosine diphosphate, thrombin, factor X, CD41, and Von-Willebrand factor levels assessed peripherally and centrally. TPF<sub>sp60/6-1:1</sub> significantly improved ZOL efficacy and accessibility to brain-receptors to a much greater extent than conventional ZOL-solution.KeywordsEndocannabinoid receptors; Epigenetically-altered genes; Hemostatic pathways; Niosomal patch; Transdermal; Zolmitriptan.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Quality by design optimization of formulation variables and process parameters for enhanced transdermal delivery of nanosuspension. 通过设计优化配方变量和工艺参数,提高纳米悬浮液的透皮给药质量。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-04 DOI: 10.1007/s13346-024-01733-4
Hiep X Nguyen, Nhi Y Le, Chien N Nguyen
{"title":"Quality by design optimization of formulation variables and process parameters for enhanced transdermal delivery of nanosuspension.","authors":"Hiep X Nguyen, Nhi Y Le, Chien N Nguyen","doi":"10.1007/s13346-024-01733-4","DOIUrl":"https://doi.org/10.1007/s13346-024-01733-4","url":null,"abstract":"<p><p>This investigation aims to fabricate, characterize, and optimize organogel containing andrographolide nanosuspension to enhance transdermal drug delivery into and across the skin in vitro. We identified the critical material attributes (CMAs) and critical process parameters (CPPs) that impact key characteristics of andrographolide nanosuspension using a systematic quality-by-design approach. We prepared andrographolide nanosuspension using the wet milling technique and evaluated various properties of the formulations. The CMAs were types and concentrations of polymers, types and concentrations of surfactants, drug concentration, and lipid concentration. The CPPs were volume of milling media and milling duration. Mean particle size, polydispersity index, encapsulation efficiency, and drug loading capacity as critical quality attributes were selected in the design for the evaluation and optimization of the formulations. Furthermore, we developed and evaluated organogel formulation to carry andrographolide nanosuspension 0.05% w/w. Drug release and permeation studies were conducted to assess the drug release kinetics and transdermal delivery of andrographolide. We presented the alteration in the average particle size, polydispersity index, encapsulation efficiency, drug-loading capacity, and drug release among various formulations to select the optimal parameters. The permeation study indicated that organogel delivered markedly more drug into the receptor fluid and skin tissue than DMSO gel (n = 3, p < 0.05). This enhancement in transdermal drug delivery was demonstrated by cumulative drug permeation after 24 h, steady-state flux, permeability coefficient, and predicted steady-state plasma concentration. Drug quantity in skin layers, total delivery, delivery efficiency, and topical selectivity were also reported. Conclusively, andrographolide nanosuspension-loaded organogel significantly increased transdermal drug delivery in vitro.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Design of charge converting lipid nanoparticles via a microfluidic coating technique. 通过微流体涂层技术设计电荷转换脂质纳米粒子。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-02-21 DOI: 10.1007/s13346-024-01538-5
Katrin Zöller, Soheil Haddadzadegan, Sera Lindner, Florina Veider, Andreas Bernkop-Schnürch
{"title":"Design of charge converting lipid nanoparticles via a microfluidic coating technique.","authors":"Katrin Zöller, Soheil Haddadzadegan, Sera Lindner, Florina Veider, Andreas Bernkop-Schnürch","doi":"10.1007/s13346-024-01538-5","DOIUrl":"10.1007/s13346-024-01538-5","url":null,"abstract":"<p><p>It was the aim of this study to design charge converting lipid nanoparticles (LNP) via a microfluidic mixing technique used for the preparation and coating of LNP. LNP consisting of 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), cholesterol, N-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (MPEG-2000-DSPE), and various cationic surfactants were prepared at diverging flow rate ratios (FRR) via microfluidic mixing. Utilizing a second chip in the microfluidic set-up, LNP were coated with polyoxyethylene (9) nonylphenol monophosphate ester (PNPP). LNP were examined for their stability in different physiologically relevant media as well as for hemolytic and cytotoxic effects. Finally, phosphate release and charge conversion of PNPP-coated LNP were evaluated after incubation with alkaline phosphatase and on Caco2-cells. LNP produced at an FRR of 5:1 exhibited a size between 80 and 150 nm and a positive zeta potential. Coating with PNPP within the second chip led to LNP exhibiting a negative zeta potential. After incubation with 1 U/ml alkaline phosphatase for 4 h, zeta potential of the LNP containing 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP) as cationic component shifted from - 35 mV to approximately + 5 mV. LNP prepared with other cationic surfactants remained slightly negative after enzymatic phosphate cleavage. Manufacturing of LNP containing PNPP and DOTAP via connection of two chips in a microfluidic instrument proves to show efficient change in zeta potential from negative to positive after incubation with alkaline phosphatase.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3173-3185"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative study of permeation effects between vibrating microneedle and low-frequency sonophoresis systems. 振动微针和低频声波电泳系统渗透效果比较研究
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-02-26 DOI: 10.1007/s13346-024-01547-4
Tingting Liu, Kai Chen, Zhigang Yan, Qiao Wang
{"title":"Comparative study of permeation effects between vibrating microneedle and low-frequency sonophoresis systems.","authors":"Tingting Liu, Kai Chen, Zhigang Yan, Qiao Wang","doi":"10.1007/s13346-024-01547-4","DOIUrl":"10.1007/s13346-024-01547-4","url":null,"abstract":"<p><p>Microneedle transdermal administration and low-frequency ultrasound represent two important physical penetration-promoting methods for enhancing drug penetration. This article aims to investigate and compare the effects of drug penetration enhancement through transdermal administration using vibrating microneedles versus low-frequency sonophoresis. In Vitro permeation studies were conducted using Valia-Chien double chamber diffusion cells to evaluate the transdermal delivery of tetramethylpyrazine hydrochloride (TMPH). The TMPH concentration in the receiving compartment was determined using high-performance liquid chromatography (HPLC). Several combinations of microneedles and ultrasound settings were investigated, including different needle heights, vibration frequencies, exposure times, and assorted distances of ultrasound horn and skin. The results revealed the vibrating microneedle system as the most efficacious treatment to increase the TMPH permeability into the rat skin. The combination of a larger needle, higher frequency, and a 3-min exposure led to a 41.92-fold increase in cumulative permeability compared to the control group. The ultrasound treatment exhibited a moderate enhancement effect on TMPH skin penetration. Using a horn-to-skin distance of 3 mm and a 3-min exposure resulted in a 4.34-fold increase in TMPH cumulative permeation compared to the control group. It could be concluded that while both the vibrating microneedle and the low-frequency ultrasound systems act as penetration enhancers for promoting the TMPH permeation through the skin, the vibrating microneedle system notably demonstrates a more effective penetration-promoting effect.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3239-3249"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microfluidic-based systems for the management of diabetes. 基于微流体的糖尿病管理系统。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-03-20 DOI: 10.1007/s13346-024-01569-y
Shuyu Zhang, Anne E Staples
{"title":"Microfluidic-based systems for the management of diabetes.","authors":"Shuyu Zhang, Anne E Staples","doi":"10.1007/s13346-024-01569-y","DOIUrl":"10.1007/s13346-024-01569-y","url":null,"abstract":"<p><p>Diabetes currently affects approximately 500 million people worldwide and is one of the most common causes of mortality in the United States. To diagnose and monitor diabetes, finger-prick blood glucose testing has long been used as the clinical gold standard. For diabetes treatment, insulin is typically delivered subcutaneously through cannula-based syringes, pens, or pumps in almost all type 1 diabetic (T1D) patients and some type 2 diabetic (T2D) patients. These painful, invasive approaches can cause non-adherence to glucose testing and insulin therapy. To address these problems, researchers have developed miniaturized blood glucose testing devices as well as microfluidic platforms for non-invasive glucose testing through other body fluids. In addition, glycated hemoglobin (HbA1c), insulin levels, and cellular biomechanics-related metrics have also been considered for microfluidic-based diabetes diagnosis. For the treatment of diabetes, insulin has been delivered transdermally through microdevices, mostly through microneedle array-based, minimally invasive injections. Researchers have also developed microfluidic platforms for oral, intraperitoneal, and inhalation-based delivery of insulin. For T2D patients, metformin, glucagon-like peptide 1 (GLP-1), and GLP-1 receptor agonists have also been delivered using microfluidic technologies. Thus far, clinical studies have been widely performed on microfluidic-based diabetes monitoring, especially glucose sensing, yet technologies for the delivery of insulin and other drugs to diabetic patients with microfluidics are still mostly in the preclinical stage. This article provides a concise review of the role of microfluidic devices in the diagnosis and monitoring of diabetes, as well as the delivery of pharmaceuticals to treat diabetes using microfluidic technologies in the recent literature.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"2989-3008"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140179440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Simple preparation and greatly improved oral bioavailability: The supersaturated drug delivery system of quercetin based on PVP K30. 制备简单,大大提高了口服生物利用度:基于 PVP K30 的槲皮素过饱和给药系统。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-02-29 DOI: 10.1007/s13346-024-01544-7
Manzhen Li, Haowen Li, Likang Lu, Jingxin Fu, Hui Ao, Meihua Han, Yifei Guo, Hongda Zhang, Zhenzhong Wang, Xiangtao Wang
{"title":"Simple preparation and greatly improved oral bioavailability: The supersaturated drug delivery system of quercetin based on PVP K30.","authors":"Manzhen Li, Haowen Li, Likang Lu, Jingxin Fu, Hui Ao, Meihua Han, Yifei Guo, Hongda Zhang, Zhenzhong Wang, Xiangtao Wang","doi":"10.1007/s13346-024-01544-7","DOIUrl":"10.1007/s13346-024-01544-7","url":null,"abstract":"<p><p>Quercetin, as a representative flavonoid, is widely present in daily diet and has been developed as a dietary supplement due to its beneficial physiological activities. However, the application of quercetin is limited due to its poor water solubility and extensive metabolism. So far, the nano-drug delivery systems designed to improve its bioavailability generally have the shortcomings of low drug loading content and difficulty in industrial production. In order to tackle these problems, quercetin supersaturated drug delivery system (QSDDS) was successfully prepared using solvent method, for which PVP K30 was employed as a crystallization and precipitation inhibitor to maintain the supersaturated state of quercetin in aqueous system. The obtained QSDDS, with a relative high drug loading content of 13%, could quickly disperse in water and form colloidal system with the mean particle size of about 200 nm, meanwhile induce the generation of supersaturated quercetin solution more than 12 h. In vivo pharmacokinetic study proved that QSDDS achieved a high absolute bioavailability of 36.05%, 10 times as that of physical quercetin suspension, which was dose-dependent with higher bioavailability at higher dose. Considering the simple preparation method, QSDDS provided a feasible strategy and a simple way to improve oral absorption of insoluble flavonoids.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3225-3238"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dynamic intervention to enhance the stability of PEGylated Ibrutinib loaded lipidic nano-vesicular systems: transitioning from colloidal dispersion to lyophilized product. 动态干预以提高 PEG 化伊布替尼负载脂质纳米囊泡系统的稳定性:从胶体分散体过渡到冻干产品。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-03-08 DOI: 10.1007/s13346-024-01555-4
Kanan Panchal, Akhila Reddy, Rishi Paliwal, Akash Chaurasiya
{"title":"Dynamic intervention to enhance the stability of PEGylated Ibrutinib loaded lipidic nano-vesicular systems: transitioning from colloidal dispersion to lyophilized product.","authors":"Kanan Panchal, Akhila Reddy, Rishi Paliwal, Akash Chaurasiya","doi":"10.1007/s13346-024-01555-4","DOIUrl":"10.1007/s13346-024-01555-4","url":null,"abstract":"<p><p>Liposomes being a promising colloidal system facilitates delivery of drugs with limited pharmacokinetic properties to achieve desirable clinical applications. However, development of a stable liposomal system is always challenging due to multiple complexities involved. Aqueous instability of liposomes and impact of various process and formulation parameters can lead to serious alteration of its therapeutic performance. In the proposed work, the authors aim to develop stable Ibrutinib-loaded liposomes using lyophilization and Quality-by-Design and assess their long-term stability. Ibrutinib-loaded liposomes were developed and optimized using Quality-by-Design technique and were further PEGylated and characterized for the same. Effect of cryoprotectants during lyophilization and other parameters are evaluated to obtain a robust formulation. The stability studies were conducted upto 6 months at various storage conditions to evaluate the effect of lyophilization. The impact of formulation, processing and lyophilization parameters on physicochemical properties of developed liposomal systems were evaluated and are critically discussed. Liquid dispersion exhibited a %degradation of 16-36% at 25 °C/60% RH which was reduced for less than 1% in lyophilized formulation for 6 months. Critical analysis and assessment of various parameters lead to identification of optimum conditions to manufacture this drug product and also opens way forward for further evaluation and translational possibilities.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3269-3290"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oxaliplatin lipidated prodrug synergistically enhances the anti-colorectal cancer effect of IL12 mRNA. 奥沙利铂脂质化原药可协同增强 IL12 mRNA 的抗结直肠癌作用。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-03-08 DOI: 10.1007/s13346-024-01540-x
Hui Liu, Yating Du, Desheng Zhan, Wenjun Yu, Yan Li, Aiping Wang, Jianpeng Yin, Haiqiang Cao, Yuanlei Fu
{"title":"Oxaliplatin lipidated prodrug synergistically enhances the anti-colorectal cancer effect of IL12 mRNA.","authors":"Hui Liu, Yating Du, Desheng Zhan, Wenjun Yu, Yan Li, Aiping Wang, Jianpeng Yin, Haiqiang Cao, Yuanlei Fu","doi":"10.1007/s13346-024-01540-x","DOIUrl":"10.1007/s13346-024-01540-x","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is the fourth most common cancer in the world, with the second highest incidence rate after lung cancer. Oxaliplatin (OXA) is a broad-spectrum anti-tumor agent with significant therapeutic efficacy in colorectal cancer, and as a divalent platinum analog, it is not selective in its distribution in the body and has systemic toxicity with continued use. Interleukin-12 (IL12) is an immunostimulatory cytokine with cytokine monotherapy that has made advances in the fight against cancer, limiting the clinical use of cytokines due to severe toxicity. Here, we introduced a long alkyl chain and N-methyl-2,2-diaminodiethylamine to the ligand of OXA to obtain OXA-LIP, which effectively reduces its toxicity and improves the uptake of the drug by tumor cells. We successfully constructed IL12 mRNA and used LNPs to deliver IL12 mRNA, and in vivo pharmacodynamic studies demonstrated that OXA-LIP combined with IL12 mRNA had better tumor inhibition and higher biosafety. In addition, it was investigated by pharmacokinetic experiments that the OXA-LIP drug could accumulate in nude mice at the tumor site, which prolonged the half-life and enhanced the anti-tumor efficiency of OXA. It is hoped that these results will provide an important reference for the subsequent research and development of OXA-LIP with IL12 mRNA, as well as provide new therapeutic approaches for the treatment of colon cancer.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3186-3199"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation. 用于眼部给药依帕司他的油凝胶:配方、体外、体内、体外和体内评估。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-05-23 DOI: 10.1007/s13346-024-01560-7
Axel Kattar, Maria Vivero-Lopez, Angel Concheiro, Rajeev Mudakavi, Anuj Chauhan, Carmen Alvarez-Lorenzo
{"title":"Oleogels for the ocular delivery of epalrestat: formulation, in vitro, in ovo, ex vivo and in vivo evaluation.","authors":"Axel Kattar, Maria Vivero-Lopez, Angel Concheiro, Rajeev Mudakavi, Anuj Chauhan, Carmen Alvarez-Lorenzo","doi":"10.1007/s13346-024-01560-7","DOIUrl":"10.1007/s13346-024-01560-7","url":null,"abstract":"<p><p>The ocular administration of lipophilic and labile drugs such as epalrestat, an aldose reductase inhibitor with potential for diabetic retinopathy treatment, demands the development of topical delivery systems capable of providing sufficient ocular bioavailability. The aim of this work was to develop non-aqueous oleogels based on soybean oil and gelators from natural and sustainable sources (ethyl cellulose, beeswax and cocoa butter) and to assess their reproducibility, safety and efficiency in epalrestat release and permeation both ex vivo and in vivo. Binary combinations of gelators at 10% w/w resulted in solid oleogels (oleorods), while single gelator oleogels at 5% w/w remained liquid at room temperature, with most of the oleogels displaying shear thinning behavior. The oleorods released up to 4 µg epalrestat per mg of oleorod in a sustained or burst pattern depending on the gelator (approx. 10% dose in 24 h). The HET-CAM assay indicated that oleogel formulations did not induce ocular irritation and were safe for topical ocular administration. Corneal and scleral ex vivo assays evidenced the permeation of epalrestat from the oleorods up to 4 and 2.5 µg/cm<sup>2</sup> after six hours, respectively. Finally, the capacity of the developed oleogels to sustain release and provide significant amounts of epalrestat to the ocular tissues was demonstrated in vivo against aqueous-based niosomes and micelles formulations loaded with the same drug concentration. Overall, the gathered information provides valuable insights into the development of oleogels for ocular drug delivery, emphasizing their safety and controlled release capabilities, which have implications for the treatment of diabetic neuropathy and other ocular conditions.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3291-3308"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11445291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141081106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Chitosan nanoparticles laden contact lenses for enzyme-triggered controlled delivery of timolol maleate: A promising strategy for managing glaucoma. 含壳聚糖纳米颗粒的隐形眼镜用于马来酸噻吗洛尔的酶触发控制给药:管理青光眼的有效策略。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2024-11-01 Epub Date: 2024-02-26 DOI: 10.1007/s13346-024-01543-8
Furqan A Maulvi, Ashmi R Patel, Kiran H Shetty, Ditixa T Desai, Dinesh O Shah, Mark D P Willcox
{"title":"Chitosan nanoparticles laden contact lenses for enzyme-triggered controlled delivery of timolol maleate: A promising strategy for managing glaucoma.","authors":"Furqan A Maulvi, Ashmi R Patel, Kiran H Shetty, Ditixa T Desai, Dinesh O Shah, Mark D P Willcox","doi":"10.1007/s13346-024-01543-8","DOIUrl":"10.1007/s13346-024-01543-8","url":null,"abstract":"<p><p>To improve drug bioavailability, eye drops can be replaced by drug-eluting contact lenses. However, issues of drug leaching from lenses during manufacture and storage, and sterilization, currently limit their commercial application. To address the issues, stimuli-(lysozyme)-sensitive chitosan nanoparticles were developed to provide controlled ocular drug delivery. Nanoparticles were prepared by ionic gelation and characterized by TEM, X-ray diffraction, DSC, and FTIR. In the flux study, conventional-soaked contact lenses (SM-TM-CL) showed high-burst release, while with direct drug-only laden contact lenses (DL-TM-CL) the drug was lost during extraction and sterilization, as well as having poor swelling and optical properties. The nanoparticle-laden contact lenses (TM-Cht-NPs) showed controlled release of timolol for 120 h in the presence of lysozyme, with acceptable opto-physical properties. In the shelf-life study, the TM-Cht-NPs contact lenses showed no leaching or alteration in the drug release pattern. In animal studies, the TM-NPs-CL lenses gave a high drug concentration in rabbit tear fluid (mean = 11.01 µg/mL for 56 h) and helped maintain a low intraocular pressure for 120 h. In conclusion, the chitosan nanoparticle-laden contact lenses demonstrated the potential application to treat glaucoma with acceptable opto-physical properties and addressed the issues of drug-leaching during sterilization and storage.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"3212-3224"},"PeriodicalIF":5.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信