Pub Date : 2024-01-01DOI: 10.2174/1567201820666230403111118
Jong-Ryul Park, Gayoung Kim, Jongho Won, Chul-Woo Kim, Donghee Park
Background: The latest technology trend in targeted drug delivery highlights stimuliresponsive particles that can release an anticancer drug in a solid tumor by responding to external stimuli.
Objective: This study aims to design, fabricate, and evaluate an ultrasound-responsive drug delivery vehicle for an ultrasound-mediated drug delivery system.
Methods: The drug-containing echogenic macroemulsion (eME) was fabricated by an emulsification method using the three phases (aqueous lipid solution as a shell, doxorubicin (DOX) contained oil, and perfluorohexane (PFH) as an ultrasound-responsive agent). The morphological structure of eMEs was investigated using fluorescence microscopy, and the size distribution was analyzed by using DLS. The echogenicity of eME was measured using a contrast-enhanced ultrasound device. The cytotoxicity was evaluated using a breast cancer cell (MDA-MB-231) via an in vitro cell experiment.
Results: The obtained eME showed an ideal morphological structure that contained both DOX and PFH in a single particle and indicated a suitable size for enhancing ultrasound response and avoiding complications in the blood vessel. The echogenicity of eME was demonstrated via an in vitro experiment, with results showcasing the potential for targeted drug delivery. Compared to free DOX, enhanced cytotoxicity and improved drug delivery efficiency in a cancer cell were proven by using DOX-loaded eMEs and ultrasound.
Conclusion: This study established a platform technology to fabricate the ultrasound-responsive vehicle. The designed drug-loaded eME could be a promising platform with ultrasound technology for targeted drug delivery.
{"title":"Evaluation of Doxorubicin-loaded Echogenic Macroemulsion for Targeted Drug Delivery.","authors":"Jong-Ryul Park, Gayoung Kim, Jongho Won, Chul-Woo Kim, Donghee Park","doi":"10.2174/1567201820666230403111118","DOIUrl":"10.2174/1567201820666230403111118","url":null,"abstract":"<p><strong>Background: </strong>The latest technology trend in targeted drug delivery highlights stimuliresponsive particles that can release an anticancer drug in a solid tumor by responding to external stimuli.</p><p><strong>Objective: </strong>This study aims to design, fabricate, and evaluate an ultrasound-responsive drug delivery vehicle for an ultrasound-mediated drug delivery system.</p><p><strong>Methods: </strong>The drug-containing echogenic macroemulsion (eME) was fabricated by an emulsification method using the three phases (aqueous lipid solution as a shell, doxorubicin (DOX) contained oil, and perfluorohexane (PFH) as an ultrasound-responsive agent). The morphological structure of eMEs was investigated using fluorescence microscopy, and the size distribution was analyzed by using DLS. The echogenicity of eME was measured using a contrast-enhanced ultrasound device. The cytotoxicity was evaluated using a breast cancer cell (MDA-MB-231) <i>via</i> an <i>in vitro</i> cell experiment.</p><p><strong>Results: </strong>The obtained eME showed an ideal morphological structure that contained both DOX and PFH in a single particle and indicated a suitable size for enhancing ultrasound response and avoiding complications in the blood vessel. The echogenicity of eME was demonstrated <i>via</i> an <i>in vitro</i> experiment, with results showcasing the potential for targeted drug delivery. Compared to free DOX, enhanced cytotoxicity and improved drug delivery efficiency in a cancer cell were proven by using DOX-loaded eMEs and ultrasound.</p><p><strong>Conclusion: </strong>This study established a platform technology to fabricate the ultrasound-responsive vehicle. The designed drug-loaded eME could be a promising platform with ultrasound technology for targeted drug delivery.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"785-793"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9247889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567201820666230523114259
Archita Kapoor, Abdul Hafeez, Poonam Kushwaha
The transport of drugs to the brain becomes a key concern when treating disorders of the central nervous system. Parkinsonism is one of the major concerns across the world populations, which causes difficulty in coordination and balance. However, the blood-brain barrier is a significant barrier to achieving optimal brain concentration through oral, transdermal, and intravenous routes of administration. The intranasal route with nanocarrier-based formulations has shown potential for managing Parkinsonism disorder (PD). Direct delivery to the brain through the intranasal route is possible via the olfactory and trigeminal pathways using drug-loaded nanotechnology-based drug delivery systems. The critical analysis of reported works demonstrates dose reduction, brain targeting, safety, effectiveness, and stability for drug-loaded nanocarriers. The important aspects of intranasal drug delivery, PD details, and nanocarrier-based intranasal formulations in PD management with a discussion of physicochemical characteristics, cell line studies, and animal studies are the major topics in this review. Patent reports and clinical investigations are summarized in the last sections.
{"title":"Nanocarrier Mediated Intranasal Drug Delivery Systems for the Management of Parkinsonism: A Review.","authors":"Archita Kapoor, Abdul Hafeez, Poonam Kushwaha","doi":"10.2174/1567201820666230523114259","DOIUrl":"10.2174/1567201820666230523114259","url":null,"abstract":"<p><p>The transport of drugs to the brain becomes a key concern when treating disorders of the central nervous system. Parkinsonism is one of the major concerns across the world populations, which causes difficulty in coordination and balance. However, the blood-brain barrier is a significant barrier to achieving optimal brain concentration through oral, transdermal, and intravenous routes of administration. The intranasal route with nanocarrier-based formulations has shown potential for managing Parkinsonism disorder (PD). Direct delivery to the brain through the intranasal route is possible via the olfactory and trigeminal pathways using drug-loaded nanotechnology-based drug delivery systems. The critical analysis of reported works demonstrates dose reduction, brain targeting, safety, effectiveness, and stability for drug-loaded nanocarriers. The important aspects of intranasal drug delivery, PD details, and nanocarrier-based intranasal formulations in PD management with a discussion of physicochemical characteristics, cell line studies, and animal studies are the major topics in this review. Patent reports and clinical investigations are summarized in the last sections.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"709-725"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9692815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567201820666230726150642
Suraj Vishwas, Swarnali Das Paul, Deepika Singh
Cancer is a diverse disease caused by transcriptional changes involving genetic and epigenetic features that influence a huge variety of genes and proteins. Skin cancer is a potentially fatal disease that affects equally men and women globally and is characterized by many molecular changes. Despite the availability of various improved approaches for detecting and treating skin cancer, it continues to be the leading cause of death throughout society. This review highlights a general overview of skin cancer, with an emphasis on epidemiology, types, risk factors, pathological and targeted facets, biomarkers and molecular markers, immunotherapy, and clinical updates of investigational drugs associated with skin cancer. The skin cancer challenges are acknowledged throughout this study, and the potential application of novel biomarkers of skin cancer formation, progression, metastasis, and prognosis is explored. Although the mechanism of skin carcinogenesis is currently poorly understood, multiple articles have shown that genetic and molecular changes are involved. Furthermore, several skin cancer risk factors are now recognized, allowing for efficient skin cancer prevention. There have been considerable improvements in the field of targeted treatment, and future research into additional targets will expand patients' therapeutic choices. In comparison to earlier articles on the same issue, this review focused on molecular and genetic factors and examined various skin cancer-related factors in depth.
{"title":"An Insight on Skin Cancer About Different Targets With Update on Clinical Trials and Investigational Drugs.","authors":"Suraj Vishwas, Swarnali Das Paul, Deepika Singh","doi":"10.2174/1567201820666230726150642","DOIUrl":"10.2174/1567201820666230726150642","url":null,"abstract":"<p><p>Cancer is a diverse disease caused by transcriptional changes involving genetic and epigenetic features that influence a huge variety of genes and proteins. Skin cancer is a potentially fatal disease that affects equally men and women globally and is characterized by many molecular changes. Despite the availability of various improved approaches for detecting and treating skin cancer, it continues to be the leading cause of death throughout society. This review highlights a general overview of skin cancer, with an emphasis on epidemiology, types, risk factors, pathological and targeted facets, biomarkers and molecular markers, immunotherapy, and clinical updates of investigational drugs associated with skin cancer. The skin cancer challenges are acknowledged throughout this study, and the potential application of novel biomarkers of skin cancer formation, progression, metastasis, and prognosis is explored. Although the mechanism of skin carcinogenesis is currently poorly understood, multiple articles have shown that genetic and molecular changes are involved. Furthermore, several skin cancer risk factors are now recognized, allowing for efficient skin cancer prevention. There have been considerable improvements in the field of targeted treatment, and future research into additional targets will expand patients' therapeutic choices. In comparison to earlier articles on the same issue, this review focused on molecular and genetic factors and examined various skin cancer-related factors in depth.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"852-869"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9876282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567201820666221220104244
Nghia Thi Phan, Yen Thi Hai Tran, Linh Tran Nguyen, Yen Kieu Hoang, Cuong Khac Bui, Hoa Dang Nguyen, Giang Thi Thu Vu
Background: Rosuvastatin, most commonly used in the form of calcium salt, belongs to the statin groups of synthetic antihyperlipidemic agents. Rosuvastatin possesses high permeability, however, its aqueous solubility is poor, causing a slow dissolution rate in water. Consequently, this dissolution rate has a decisive role in the release and absorption of rosuvastatin in the gastrointestinal tube.
Objective: The aims of this study were to evaluate the absorption of the drug from the self-nano emulsifying drug delivery system of rosuvastatin (Ros SNEDDS) compared to rosuvastatin substance and to develop a level-A in vitro-in vivo correlation (IVIVC) for Ros SNEDDS.
Methods: An in-house developed LC-MS/MS method was used to determine the concentrations of rosuvastatin in dog plasma. Six beagle dogs received an intravenous dose, Ros SNEDDS, rosuvastatin substance. In vitro dissolution of the Ros SNEDDS was carried out with different conditions. Correlation models were developed from the dissolution and absorption results of Ros SNEDDS.
Results: The results showed a 1.7-fold enhanced oral bioavailability and 2.1-time increase of rosuvastatin Cmax in Ros SNEDDS form, compared to the rosuvastatin substance. A 900 ml dissolution medium of pH of 6.6 has demonstrated its suitability, the in vitro dissolution model was studied and supported by the Weibull equation with a weighting factor of 1/y2 as it presented the lowest values of AIC.
Conclusion: Ros SNEDDS demonstrated higher bioavailability of rosuvastatin in comparison to rosuvastatin substance and established a level A IVIVC used in future bioequivalence trials.
{"title":"Self Nanoelmusifying Drug Delivery System of Rosuvastatin: Bioavailability Evaluation and <i>In vitro</i> - <i>In vivo</i> Correlation.","authors":"Nghia Thi Phan, Yen Thi Hai Tran, Linh Tran Nguyen, Yen Kieu Hoang, Cuong Khac Bui, Hoa Dang Nguyen, Giang Thi Thu Vu","doi":"10.2174/1567201820666221220104244","DOIUrl":"10.2174/1567201820666221220104244","url":null,"abstract":"<p><strong>Background: </strong>Rosuvastatin, most commonly used in the form of calcium salt, belongs to the statin groups of synthetic antihyperlipidemic agents. Rosuvastatin possesses high permeability, however, its aqueous solubility is poor, causing a slow dissolution rate in water. Consequently, this dissolution rate has a decisive role in the release and absorption of rosuvastatin in the gastrointestinal tube.</p><p><strong>Objective: </strong>The aims of this study were to evaluate the absorption of the drug from the self-nano emulsifying drug delivery system of rosuvastatin (Ros SNEDDS) compared to rosuvastatin substance and to develop a level-A <i>in vitro-in vivo</i> correlation (IVIVC) for Ros SNEDDS.</p><p><strong>Methods: </strong>An in-house developed LC-MS/MS method was used to determine the concentrations of rosuvastatin in dog plasma. Six beagle dogs received an intravenous dose, Ros SNEDDS, rosuvastatin substance. <i>In vitro</i> dissolution of the Ros SNEDDS was carried out with different conditions. Correlation models were developed from the dissolution and absorption results of Ros SNEDDS.</p><p><strong>Results: </strong>The results showed a 1.7-fold enhanced oral bioavailability and 2.1-time increase of rosuvastatin C<sub>max</sub> in Ros SNEDDS form, compared to the rosuvastatin substance. A 900 ml dissolution medium of pH of 6.6 has demonstrated its suitability, the <i>in vitro</i> dissolution model was studied and supported by the Weibull equation with a weighting factor of 1/y<sup>2</sup> as it presented the lowest values of AIC.</p><p><strong>Conclusion: </strong>Ros SNEDDS demonstrated higher bioavailability of rosuvastatin in comparison to rosuvastatin substance and established a level A IVIVC used in future bioequivalence trials.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"734-743"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10764183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567201820666230328122504
Nurlan Ismailovi, H Tuba Kıyan, A Alper Öztürk
Background: Numerous pharmaceutical applications for chitosan, a polysaccharide made from the shells of crustaceans by deacetylating chitin that occurs naturally, are currently being researched. Chitosan, a natural polymer, is successfully used to prepare many drug-carrier systems, such as gel, film, nanoparticle, and wound dressing.
Objective: Preparing chitosan gels without external crosslinkers is less toxic and environmentally friendly.
Methods: Chitosan-based gels containing Helichrysum pamphylicum P.H. Davis & Kupicha methanolic extract (HP) were produced successfully.
Results: The F9-HP coded gel prepared with high molecular weight chitosan was chosen as the optimum formulation in terms of pH and rheological properties. The amount of HP was found to be 98.83% ± 0.19 in the F9-HP coded formulation. The HP release from the F9-HP coded formula was determined to be slower and 9 hours prolonged release compared to pure HP. It was determined that HP release from F9-HP coded formulation with the DDSolver program was by anomalous (non-fickian) diffusion mechanism. The F9-HP coded formulation significantly showed DPPH free radical scavenger, ABTS•+ cation decolorizing and metal chelating antioxidant activity while weakly reducing antioxidant potential. According to the HET-CAM scores, strong anti-inflammatory activity was obtained by the F9-HP coded gel at a dose of 20 μg.embryo-1 (p<0.05 compared with SDS).
Conclusion: In conclusion, it can be said that chitosan-based gels containing HP, which can be used in both antioxidant and anti-inflammatory treatment, were successfully formulated and characterized.
背景:壳聚糖是从甲壳类动物的甲壳中通过脱乙酰化天然存在的甲壳素而制成的一种多糖,目前正在研究壳聚糖的许多药物应用。壳聚糖是一种天然聚合物,已成功用于制备多种药物载体系统,如凝胶、薄膜、纳米粒子和伤口敷料:目标:制备壳聚糖凝胶时无需外加交联剂,毒性较低且对环境友好:方法:成功制备了含有Helichrysum pamphylicum P.H.Davis & Kupicha甲醇提取物(HP)的壳聚糖凝胶:结果:使用高分子量壳聚糖制备的 F9-HP 编码凝胶在 pH 值和流变特性方面被选为最佳配方。在 F9-HP 编码配方中,HP 的含量为 98.83 %± 0.19。经测定,F9-HP 编码配方中 HP 的释放速度较慢,与纯 HP 相比,释放时间延长了 9 小时。通过 DDSolver 程序确定,F9-HP 编码配方的 HP 释放是通过反常(非费克)扩散机制进行的。F9-HP 编码配方具有明显的 DPPH 自由基清除剂、ABTS-+ 阳离子脱色和金属螯合抗氧化活性,同时具有微弱的还原抗氧化潜力。根据 HET-CAM 评分,F9-HP 编码凝胶在剂量为 20 µg.embryo-1 时具有较强的抗炎活性(pConclusion):总之,可以说含有 HP 的壳聚糖基凝胶已成功配制并定性,可用于抗氧化和抗炎治疗。
{"title":"A Novel Phytotherapy Application: Preparation, Characterization, Antioxidant Activities and Determination of Anti-inflammatory Effects by <i>In vivo</i> HET-CAM Assay of Chitosan-based DDSs Containing Endemic <i>Helichrysum pamphylicum</i> P.H. Davis & Kupicha Methanolic Extract.","authors":"Nurlan Ismailovi, H Tuba Kıyan, A Alper Öztürk","doi":"10.2174/1567201820666230328122504","DOIUrl":"10.2174/1567201820666230328122504","url":null,"abstract":"<p><strong>Background: </strong>Numerous pharmaceutical applications for chitosan, a polysaccharide made from the shells of crustaceans by deacetylating chitin that occurs naturally, are currently being researched. Chitosan, a natural polymer, is successfully used to prepare many drug-carrier systems, such as gel, film, nanoparticle, and wound dressing.</p><p><strong>Objective: </strong>Preparing chitosan gels without external crosslinkers is less toxic and environmentally friendly.</p><p><strong>Methods: </strong>Chitosan-based gels containing <i>Helichrysum pamphylicum</i> P.H. Davis & Kupicha methanolic extract (HP) were produced successfully.</p><p><strong>Results: </strong>The F9-HP coded gel prepared with high molecular weight chitosan was chosen as the optimum formulation in terms of pH and rheological properties. The amount of HP was found to be 98.83% ± 0.19 in the F9-HP coded formulation. The HP release from the F9-HP coded formula was determined to be slower and 9 hours prolonged release compared to pure HP. It was determined that HP release from F9-HP coded formulation with the DDSolver program was by anomalous (non-fickian) diffusion mechanism. The F9-HP coded formulation significantly showed DPPH free radical scavenger, ABTS•+ cation decolorizing and metal chelating antioxidant activity while weakly reducing antioxidant potential. According to the HET-CAM scores, strong anti-inflammatory activity was obtained by the F9-HP coded gel at a dose of 20 μg.embryo<sup>-1 </sup>(p<0.05 compared with SDS).</p><p><strong>Conclusion: </strong>In conclusion, it can be said that chitosan-based gels containing HP, which can be used in both antioxidant and anti-inflammatory treatment, were successfully formulated and characterized.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"901-916"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11071655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9607425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567201820666230508121716
Amisha, Dilpreet Singh, Balak Das Kurmi, Amrinder Singh
Atopic dermatitis (AD), commonly known as Eczema, is a non-communicable skin condition that tends to become chronic. The deteriorating immunological abnormalities are marked by mild to severe erythema, severe itching, and recurrent eczematous lesions. Different pharmacological approaches are used to treat AD. The problem with commercial topical preparations lies in the limitation of skin atrophy, systemic side effects, and burning sensation that decreases patient compliance. The carrier-based system promises to eliminate these shortcomings; thus, a novel approach to treating AD is required. Liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanoemulsions, etc., have been developed recently to address this ailment. Despite extensive research in the development method and various techniques, it has been challenging to demonstrate the commercial feasibility of these carrier- based systems, which illustrates a gap among the different research areas. Further, different soft wares and other tools have proliferated among biochemists as part of a cooperative approach to drug discovery. It is crucial in designing, developing, and analyzing processes in the pharmaceutical industry and is widely used to reduce costs, accelerate the development of biologically innovative active ingredients, and shorten the development time. This review sheds light on the compilation of extensive efforts to combat this disease, the product development processes, commercial products along with patents in this regard, numerous options for each step of computer-aided drug design, including in silico pharmacokinetics, pharmacodynamics, and toxicity screening or predictions that are important in finding the drug-like compounds.
特应性皮炎(AD)俗称湿疹,是一种慢性非传染性皮肤病。不断恶化的免疫异常表现为轻度至重度红斑、剧烈瘙痒和反复发作的湿疹皮损。治疗 AD 的药物方法多种多样。市售外用制剂的问题在于皮肤萎缩、全身副作用和灼热感,这些都降低了患者的依从性。以载体为基础的系统有望消除这些缺点;因此,需要一种治疗 AD 的新方法。最近,人们开发了脂质体、微乳剂、固体脂质纳米颗粒(SLNs)、纳米乳剂等,以解决这一问题。尽管在开发方法和各种技术方面进行了广泛的研究,但要证明这些基于载体的系统的商业可行性仍具有挑战性,这说明了不同研究领域之间的差距。此外,作为药物发现合作方法的一部分,不同的软工具和其他工具已在生物化学家中大量出现。它在制药业的设计、开发和分析过程中至关重要,并被广泛用于降低成本、加快生物创新活性成分的开发和缩短开发时间。这篇综述揭示了为防治这种疾病所做的大量努力、产品开发过程、商业产品以及这方面的专利、计算机辅助药物设计每个步骤的众多选择,包括对寻找类药物化合物非常重要的默克药代动力学、药效学和毒性筛选或预测。
{"title":"Recent Advances in Nanocarrier-based Approaches to Atopic Dermatitis and Emerging Trends in Drug Development and Design.","authors":"Amisha, Dilpreet Singh, Balak Das Kurmi, Amrinder Singh","doi":"10.2174/1567201820666230508121716","DOIUrl":"10.2174/1567201820666230508121716","url":null,"abstract":"<p><p>Atopic dermatitis (AD), commonly known as Eczema, is a non-communicable skin condition that tends to become chronic. The deteriorating immunological abnormalities are marked by mild to severe erythema, severe itching, and recurrent eczematous lesions. Different pharmacological approaches are used to treat AD. The problem with commercial topical preparations lies in the limitation of skin atrophy, systemic side effects, and burning sensation that decreases patient compliance. The carrier-based system promises to eliminate these shortcomings; thus, a novel approach to treating AD is required. Liposomes, microemulsions, solid lipid nanoparticles (SLNs), nanoemulsions, etc., have been developed recently to address this ailment. Despite extensive research in the development method and various techniques, it has been challenging to demonstrate the commercial feasibility of these carrier- based systems, which illustrates a gap among the different research areas. Further, different soft wares and other tools have proliferated among biochemists as part of a cooperative approach to drug discovery. It is crucial in designing, developing, and analyzing processes in the pharmaceutical industry and is widely used to reduce costs, accelerate the development of biologically innovative active ingredients, and shorten the development time. This review sheds light on the compilation of extensive efforts to combat this disease, the product development processes, commercial products along with patents in this regard, numerous options for each step of computer-aided drug design, including in silico pharmacokinetics, pharmacodynamics, and toxicity screening or predictions that are important in finding the drug-like compounds.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"932-960"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9432294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567201820666230119120314
Ailing Hui, Zheng Zhang, Jinghe Wang, Li Yang, Shaohuan Deng, Wencheng Zhang, An Zhou, Zeyu Wu
Background: Borneol can enhance the blood-brain barrier (BBB) permeability of some drugs and suppress the efflux transport of P-glycoprotein (P-gp), which will contribute to the brain delivery of salvianic acid A (SAA).
Objective: The study aimed to develop an approach to improve the brain targeting delivery of SAA with the aid of borneol.
Materials and methods: "Borneol" was involved in SAA via esterified prodrug SAA borneol ester (SBE) and combined administration (SAA-borneol, SAA-B). Subsequently, the blood-brain transport of SAA through brain/blood distribution and P-gp regulation via expression and function assay were investigated in rats.
Results: The SBE and SAA-B-treated group received a three-fold brain concentration and longer t1/2 and retention period of active SAA than that of SAA alone (20.18/13.82 min vs. 6.48 min; 18.30/17.42 min vs. 11.46 min). In addition, blood to brain transport of active SAA in SBE was altered in comparison to that of SAA-B, ultimately resulting in a better drug targeting index (9.93 vs. 3.63). Further studies revealed that SBE-induced downregulation of P-gp expression occurred at the later stage of administration (60 min, P < 0.01), but SBE always showed a more powerful drug transport activity across BBB represented by Kp value of rhodamine 123 than SAA-B (30, 60 min, P < 0.05).
Conclusion: The comparative results indicate that SBE exhibits prominent efficiency on SAA's targeting delivery through improved blood/brain metabolic properties and sustained inhibitory effect of "borneol" on P-gp efflux. Therefore, prodrug modification can be applied as a more effective approach for brain delivery of SAA.
背景:硼乙醇可以增强某些药物的血脑屏障(BBB)通透性,抑制P-糖蛋白(P-gp)的外流转运,从而有助于丹酚酸A(SAA)的脑部给药:该研究旨在开发一种方法,借助博奈醇改善SAA的脑靶向递送:"硼醇 "通过酯化原药SAA硼醇酯(SBE)和联合给药(SAA-硼醇,SAA-B)参与SAA。随后,在大鼠体内研究了 SAA 通过脑/血分布的血脑转运以及通过表达和功能检测对 P-gp 的调控:结果:SBE和SAA-B处理组的脑内活性SAA浓度是单用SAA组的三倍,t1/2和滞留期也更长(20.18/13.82 min vs. 6.48 min; 18.30/17.42 min vs. 11.46 min)。此外,与 SAA-B 相比,SBE 中活性 SAA 从血液到大脑的转运发生了改变,最终导致了更好的药物靶向指数(9.93 vs. 3.63)。进一步的研究发现,SBE诱导的P-gp表达下调发生在给药的后期(60分钟,P<0.01),但与SAA-B相比,SBE始终表现出更强的药物跨BBB转运活性(以罗丹明123的Kp值表示)(30、60分钟,P<0.05):比较结果表明,SBE通过改善血液/脑代谢特性和 "borneol "对P-gp外流的持续抑制作用,对SAA的靶向递送具有显著效果。因此,原药修饰可以作为一种更有效的方法用于 SAA 的脑部给药。
{"title":"Enhanced Brain Targeting Delivery of Salvianic Acid Using Borneol as a Promoter of Blood/Brain Transport and Regulator of P-gp.","authors":"Ailing Hui, Zheng Zhang, Jinghe Wang, Li Yang, Shaohuan Deng, Wencheng Zhang, An Zhou, Zeyu Wu","doi":"10.2174/1567201820666230119120314","DOIUrl":"10.2174/1567201820666230119120314","url":null,"abstract":"<p><strong>Background: </strong>Borneol can enhance the blood-brain barrier (BBB) permeability of some drugs and suppress the efflux transport of P-glycoprotein (P-gp), which will contribute to the brain delivery of salvianic acid A (SAA).</p><p><strong>Objective: </strong>The study aimed to develop an approach to improve the brain targeting delivery of SAA with the aid of borneol.</p><p><strong>Materials and methods: </strong>\"Borneol\" was involved in SAA <i>via</i> esterified prodrug SAA borneol ester (SBE) and combined administration (SAA-borneol, SAA-B). Subsequently, the blood-brain transport of SAA through brain/blood distribution and P-gp regulation <i>via</i> expression and function assay were investigated in rats.</p><p><strong>Results: </strong>The SBE and SAA-B-treated group received a three-fold brain concentration and longer t1/2 and retention period of active SAA than that of SAA alone (20.18/13.82 min vs. 6.48 min; 18.30/17.42 min vs. 11.46 min). In addition, blood to brain transport of active SAA in SBE was altered in comparison to that of SAA-B, ultimately resulting in a better drug targeting index (9.93 vs. 3.63). Further studies revealed that SBE-induced downregulation of P-gp expression occurred at the later stage of administration (60 min, <i>P</i> < 0.01), but SBE always showed a more powerful drug transport activity across BBB represented by Kp value of rhodamine 123 than SAA-B (30, 60 min, <i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>The comparative results indicate that SBE exhibits prominent efficiency on SAA's targeting delivery through improved blood/brain metabolic properties and sustained inhibitory effect of \"borneol\" on P-gp efflux. Therefore, prodrug modification can be applied as a more effective approach for brain delivery of SAA.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"726-733"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10550998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01DOI: 10.2174/1567201820666230203115752
Rohitas Deshmukh, Aman Kumar Jain, Rajesh Singh, Swarnali Das Paul, Ranjit K Harwansh
Cancer is one of the deadliest illnesses of the 21st century. Chemotherapy and radiation therapies both have considerable side effects. Antitumor antibiotics are one of them. Coughs, common colds, fevers, laryngitis, and infectious disorders have all been treated with Andrographis paniculata for centuries. Extracts of Andrographis effectively treat various ailments, as well as cancer. The most active molecule in Andrographis paniculata is andrographolide a, diterpene, and lactone. Andrographis paniculata and its derivatives have long been used to treat various ailments. Anti-inflammatory and cancerfighting characteristics have been observed in Andrographolide. Andrographolide, a diterpene lactone separated from Andrographis paniculata, has also been shown to have important criticalessential biological protective properties. It has also been suggested that it could be used to treat major human diseases like-rheumatoid like rheumatoid, colitis, and Parkinsons disease. This summary aims to highlight Andrographolide as a promising cancer treatment option. Several databases were searched for andrographolides cytotoxic/anti-cancer effects in pre-clinical and clinical research to serve this purpose. Several studies have shown that Andrographolide is helpful in cancer medication, as detailed in this review.
{"title":"<i>Andrographis paniculata</i> and Andrographolide - A Snapshot on Recent Advances in Nano Drug Delivery Systems against Cancer.","authors":"Rohitas Deshmukh, Aman Kumar Jain, Rajesh Singh, Swarnali Das Paul, Ranjit K Harwansh","doi":"10.2174/1567201820666230203115752","DOIUrl":"10.2174/1567201820666230203115752","url":null,"abstract":"<p><p>Cancer is one of the deadliest illnesses of the 21st century. Chemotherapy and radiation therapies both have considerable side effects. Antitumor antibiotics are one of them. Coughs, common colds, fevers, laryngitis, and infectious disorders have all been treated with <i>Andrographis paniculata</i> for centuries. Extracts of <i>Andrographis</i> effectively treat various ailments, as well as cancer. The most active molecule in <i>Andrographis paniculata</i> is andrographolide a, diterpene, and lactone. <i>Andrographis paniculata</i> and its derivatives have long been used to treat various ailments. Anti-inflammatory and cancerfighting characteristics have been observed in Andrographolide. Andrographolide, a diterpene lactone separated from <i>Andrographis paniculata</i>, has also been shown to have important criticalessential biological protective properties. It has also been suggested that it could be used to treat major human diseases like-rheumatoid like rheumatoid, colitis, and Parkinsons disease. This summary aims to highlight Andrographolide as a promising cancer treatment option. Several databases were searched for andrographolides cytotoxic/anti-cancer effects in pre-clinical and clinical research to serve this purpose. Several studies have shown that Andrographolide is helpful in cancer medication, as detailed in this review.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"631-644"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10653230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The application of therapeutically active molecules through the dermal/transdermal route into the skin has evolved as an attractive formulation strategy in comparison to oral delivery systems for the treatment of various disease conditions. However, the delivery of drugs across the skin is limited due to poor permeability. Dermal/transdermal delivery is associated with ease of accessibility, enhanced safety, better patient compliance, and reduced variability in plasma drug concentrations. It has the ability to bypass the first-pass metabolism, which ultimately results in steady and sustained drug levels in the systemic circulation. Vesicular drug delivery systems, including bilosomes, have gained significant interest due to their colloidal nature, improved drug solubility, absorption, and bioavailability with prolonged circulation time for a large number of new drug molecules. Bilosomes are novel lipid vesicular nanocarriers comprising bile salts, such as deoxycholic acid, sodium cholate, deoxycholate, taurocholate, glycocholate or sorbitan tristearate. These bilosomes are associated with high flexibility, deformability, and elasticity attributed to their bile acid component. These carriers are advantageous in terms of improved skin permeation, increased dermal and epidermal drug concentration, and enhanced local action with reduced systemic absorption of the drug, resulting in reduced side effects. The present article provides a comprehensive overview of the biopharmaceutical aspects of dermal/transdermal bilosome delivery systems, their composition, formulation techniques, characterization methods, and applications.
{"title":"Novel Vesicular Bilosomal Delivery Systems for Dermal/Transdermal Applications.","authors":"Vasanti Suvarna, Rashmi Mallya, Kajal Deshmukh, Bhakti Sawant, Tabassum Asif Khan, Abdelwahab Omri","doi":"10.2174/1567201820666230707161206","DOIUrl":"10.2174/1567201820666230707161206","url":null,"abstract":"<p><p>The application of therapeutically active molecules through the dermal/transdermal route into the skin has evolved as an attractive formulation strategy in comparison to oral delivery systems for the treatment of various disease conditions. However, the delivery of drugs across the skin is limited due to poor permeability. Dermal/transdermal delivery is associated with ease of accessibility, enhanced safety, better patient compliance, and reduced variability in plasma drug concentrations. It has the ability to bypass the first-pass metabolism, which ultimately results in steady and sustained drug levels in the systemic circulation. Vesicular drug delivery systems, including bilosomes, have gained significant interest due to their colloidal nature, improved drug solubility, absorption, and bioavailability with prolonged circulation time for a large number of new drug molecules. Bilosomes are novel lipid vesicular nanocarriers comprising bile salts, such as deoxycholic acid, sodium cholate, deoxycholate, taurocholate, glycocholate or sorbitan tristearate. These bilosomes are associated with high flexibility, deformability, and elasticity attributed to their bile acid component. These carriers are advantageous in terms of improved skin permeation, increased dermal and epidermal drug concentration, and enhanced local action with reduced systemic absorption of the drug, resulting in reduced side effects. The present article provides a comprehensive overview of the biopharmaceutical aspects of dermal/transdermal bilosome delivery systems, their composition, formulation techniques, characterization methods, and applications.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"961-977"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10123080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deformable lipidic-nano carriers are a category of advanced liposomal formulations. Deformable lipidic-nano carriers have a specific character to transform by rearranging the lipidic backbone to squeeze themself through a pore opening ten times smaller than their diameter when exposed to a variable condition like hydration gradient as these have potentially been used as a non-invasive delivery system to transdermally migrate various therapeutic agents for over three decades. Despite their vast application in transdermal drug delivery system, non-uniformity to express their chemical nature still exist and authors use various terms synonymously and interchangeably with each other. The present study delineates the terminologies used to express different derived deformable vesicular carriers to harmonize the terminological use. It also includes the effectiveness of deformable nanocarriers like Transferosomes, Ethosomes, Menthosomes, Invasomes, and Glycerosomes in skin conditions like basal cell carcinoma, fungal and viral infections, and hyperpigmentation disorders, along with others. Various review and research articles were selected from the 'Pubmed' database. The keywords like Transferosomes, Flexi-vesicular system, ultra-deformable vesicles, and nano-vesicular systems were used to extract the data. The data was reviewed and compiled to categorically classify different flexible vesicular systems. The composition of the different vesicular systems is identified and a report of various pathological conditions where the use of flexible lipid nanocarrier systems was implemented is compiled. The review also offers suggestive approaches where the applicability of these systems can be explored further.
{"title":"Exploring Applications of Flexible Vesicular Systems as Transdermal Drug Delivery.","authors":"Palwinder Kaur, Surajpal Verma, Bhupendra Tomar, Manish Vyas, Violina Kakoty, Paramita Saha, Sarathlal Kalarikkal Chandran","doi":"10.2174/1567201821666230830125253","DOIUrl":"10.2174/1567201821666230830125253","url":null,"abstract":"<p><p>Deformable lipidic-nano carriers are a category of advanced liposomal formulations. Deformable lipidic-nano carriers have a specific character to transform by rearranging the lipidic backbone to squeeze themself through a pore opening ten times smaller than their diameter when exposed to a variable condition like hydration gradient as these have potentially been used as a non-invasive delivery system to transdermally migrate various therapeutic agents for over three decades. Despite their vast application in transdermal drug delivery system, non-uniformity to express their chemical nature still exist and authors use various terms synonymously and interchangeably with each other. The present study delineates the terminologies used to express different derived deformable vesicular carriers to harmonize the terminological use. It also includes the effectiveness of deformable nanocarriers like Transferosomes, Ethosomes, Menthosomes, Invasomes, and Glycerosomes in skin conditions like basal cell carcinoma, fungal and viral infections, and hyperpigmentation disorders, along with others. Various review and research articles were selected from the 'Pubmed' database. The keywords like Transferosomes, Flexi-vesicular system, ultra-deformable vesicles, and nano-vesicular systems were used to extract the data. The data was reviewed and compiled to categorically classify different flexible vesicular systems. The composition of the different vesicular systems is identified and a report of various pathological conditions where the use of flexible lipid nanocarrier systems was implemented is compiled. The review also offers suggestive approaches where the applicability of these systems can be explored further.</p>","PeriodicalId":10842,"journal":{"name":"Current drug delivery","volume":" ","pages":"1062-1072"},"PeriodicalIF":2.4,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10495155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}