Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, such as ineffective targeting, larger doses, toxicity to healthy cells and side effects, have prompted attention to alternate approaches to address these difficulties. RNA interference by small interfering RNA (siRNA) is one such tactic. When compared with chemotherapy, siRNA has several advantages, including the ability to quickly modify and suppress the expression of the target gene and display superior efficacy and safety. However, there are known challenges and hurdles that limits their clinical translation. Decomposition by endonucleases, renal clearance, hydrophilicity, negative surface charge, short half-life and off-target effects of naked siRNA are obstacles that hinder the desired biological activity of naked siRNA. Nanoparticulate systems such as polymeric, lipid, lipid-polymeric, metallic, mesoporous silica nanoparticles and several other nanocarriers were used for effective delivery of siRNA and to knock down genes involved in breast cancer and triple-negative breast cancer. The focus of this review is to provide a comprehensive picture of various strategies utilized for delivering siRNA, such as combinatorial delivery, development of modified nanoparticles, smart nanocarriers and nanocarriers that target angiogenesis, cancer stem cells and metastasis of breast cancer.
{"title":"Therapeutic delivery of siRNA for the management of breast cancer and triple-negative breast cancer.","authors":"Boya Manasa Sai, Yirivinti Hayagreeva Dinakar, Hitesh Kumar, Rupshee Jain, Sharyu Kesharwani, Siddharth S Kesharwani, Shyam Lal Mudavath, Ajmeer Ramkishan, Vikas Jain","doi":"10.1080/20415990.2024.2400044","DOIUrl":"10.1080/20415990.2024.2400044","url":null,"abstract":"<p><p>Breast cancer is the leading cause of cancer-related deaths among women globally. The difficulties with anticancer medications, such as ineffective targeting, larger doses, toxicity to healthy cells and side effects, have prompted attention to alternate approaches to address these difficulties. RNA interference by small interfering RNA (siRNA) is one such tactic. When compared with chemotherapy, siRNA has several advantages, including the ability to quickly modify and suppress the expression of the target gene and display superior efficacy and safety. However, there are known challenges and hurdles that limits their clinical translation. Decomposition by endonucleases, renal clearance, hydrophilicity, negative surface charge, short half-life and off-target effects of naked siRNA are obstacles that hinder the desired biological activity of naked siRNA. Nanoparticulate systems such as polymeric, lipid, lipid-polymeric, metallic, mesoporous silica nanoparticles and several other nanocarriers were used for effective delivery of siRNA and to knock down genes involved in breast cancer and triple-negative breast cancer. The focus of this review is to provide a comprehensive picture of various strategies utilized for delivering siRNA, such as combinatorial delivery, development of modified nanoparticles, smart nanocarriers and nanocarriers that target angiogenesis, cancer stem cells and metastasis of breast cancer.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11498026/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aim: This study was conducted to investigate the effect of fibrin glue-CM11 antibacterial peptide mixture (FG-P) on the healing of infected wounds in vivo.Materials & methods: We formulated a mixture of FG-P and evaluated its antimicrobial activity in vitro against multidrug-resistant (MDR) bacteria involved in wound infection as well as its healing effect on wound infected by methicillin-resistant S. aureus (MRSA) in vivo.Results: The peptide had an MIC of 8 μg/ml against all bacteria isolates. Growth inhibition zones were evident for FG-P compared with FG. The in vivo study showed that the FG-P could be significantly effective in healing the MRSA-infected wound.Conclusion: The use of FG-P mixture is a very suitable option for treating infected wounds.
{"title":"Antimicrobial peptide-fibrin glue mixture for treatment of methicillin-resistant <i>Staphylococcus aureus</i>-infected wounds.","authors":"Mehran Bahreini, Mehrdad Moosazadeh Moghaddam, Masoud Ghorbani, Mohammad Reza Nourani, Reza Mirnejad","doi":"10.1080/20415990.2024.2369497","DOIUrl":"10.1080/20415990.2024.2369497","url":null,"abstract":"<p><p><b>Aim:</b> This study was conducted to investigate the effect of fibrin glue-CM11 antibacterial peptide mixture (FG-P) on the healing of infected wounds <i>in vivo</i>.<b>Materials & methods:</b> We formulated a mixture of FG-P and evaluated its antimicrobial activity <i>in vitro</i> against multidrug-resistant (MDR) bacteria involved in wound infection as well as its healing effect on wound infected by methicillin-resistant <i>S. aureus</i> (MRSA) <i>in vivo</i>.<b>Results:</b> The peptide had an MIC of 8 μg/ml against all bacteria isolates. Growth inhibition zones were evident for FG-P compared with FG. The <i>in vivo</i> study showed that the FG-P could be significantly effective in healing the MRSA-infected wound.<b>Conclusion:</b> The use of FG-P mixture is a very suitable option for treating infected wounds.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sphingolipids (SL) are well recognized for their cell signaling through extracellular and intracellular pathways. Based on chemistry different types of SL are biosynthesized in mammalian cells and have specific function in cellular activity. SL has an ampiphilic structure with have hydrophobic body attached to the polar head enables their use as a drug delivery agent in the form of nanocarriers. SL-based liposomes can improve the solubility of lipophilic drugs through host and drug complexes and are more stable than conventional liposomal formulations. Preclinical studies of SL nanocarriers are reported on topical delivery, oral delivery, ocular delivery, chemotherapeutic delivery, cardiovascular delivery and Alzheimer's disease. The commercial challenges and patents related to SL nanoformulations are highlighted in this article.
{"title":"Application of sphingolipid-based nanocarriers in drug delivery: an overview.","authors":"Samarth Kumar, Ajit Singh, Prachi Pandey, Ajay Khopade, Krutika K Sawant","doi":"10.1080/20415990.2024.2377066","DOIUrl":"10.1080/20415990.2024.2377066","url":null,"abstract":"<p><p>Sphingolipids (SL) are well recognized for their cell signaling through extracellular and intracellular pathways. Based on chemistry different types of SL are biosynthesized in mammalian cells and have specific function in cellular activity. SL has an ampiphilic structure with have hydrophobic body attached to the polar head enables their use as a drug delivery agent in the form of nanocarriers. SL-based liposomes can improve the solubility of lipophilic drugs through host and drug complexes and are more stable than conventional liposomal formulations. Preclinical studies of SL nanocarriers are reported on topical delivery, oral delivery, ocular delivery, chemotherapeutic delivery, cardiovascular delivery and Alzheimer's disease. The commercial challenges and patents related to SL nanoformulations are highlighted in this article.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-10-03DOI: 10.1080/20415990.2024.2406226
Abrahem Sayed, Pranesh Ravichandran, Cecilia Canizela, Rehan M Hussain
EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.
EYP-1901(Duravyu)在治疗新生血管性老年性黄斑变性(nAMD)和糖尿病性黄斑水肿(DME)/糖尿病视网膜病变的 I 期和 II 期临床试验中取得了良好的疗效。Vorolanib 是一种针对血管内皮生长因子所有异构体的抑制剂,这种创新疗法利用了 Vorolanib 的强效抗血管生成特性,有效缓解了支撑这些视网膜病变的病理性新生血管和血管通透性。EYP-1901 与 Durasert 给药系统集成,可直接向眼球后段持续释放沃罗来尼。这种给药系统可确保长期持续的治疗效果,并大大减少所需的临床干预频率,在保证患者安全的同时提供更方便的治疗方案。
{"title":"Role of EYP-1901 in neovascular age-related macular degeneration and diabetic eye diseases: review of Phase I/II trials.","authors":"Abrahem Sayed, Pranesh Ravichandran, Cecilia Canizela, Rehan M Hussain","doi":"10.1080/20415990.2024.2406226","DOIUrl":"10.1080/20415990.2024.2406226","url":null,"abstract":"<p><p>EYP-1901 (Duravyu) has demonstrated promising outcomes in Phases I and II clinical trials for the treatment of neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME)/diabetic retinopathy. This innovative treatment capitalizes on the potent anti-angiogenic properties of vorolanib, an inhibitor that targets all isoforms of VEGF, effectively mitigating the pathological neovascularization and vascular permeability that underpin these retinal conditions. EYP-1901 is integrated with the Durasert drug delivery system to administer a sustained release of vorolanib directly to the posterior segment of the eye. This delivery system ensures a consistent therapeutic effect over an extended period and significantly reduces the frequency of clinical interventions required, offering a more convenient treatment regimen while maintaining patient safety.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-07-01DOI: 10.1080/20415990.2024.2363136
Debadatta Mohapatra, Prakash Ch Senapati, Shantibhusan Senapati, Vivek Pandey, Pawan K Dubey, Sanjay Singh, Alakh N Sahu
Aim: The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy.Materials & methods: The ME was formulated using Cinnamon oil & Tween® 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Zavg) and polydispersity index (PDI).Results: The DSF-loaded optimized stable ME showed enhanced dissolution, in-vitro cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF.Conclusion: Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.
目的:本研究旨在通过质量源于设计(QbD)方法开发和优化微乳剂(ME),以改善水溶性差的药物双硫仑(DSF)的水溶性和溶解性,从而重新用于黑色素瘤和乳腺癌的治疗。材料与方法:使用肉桂油和吐温®80配制ME,并采用基于D-最佳混合物设计的QbD方法进行统计优化,以开发出具有低囊泡尺寸(Zavg)和多分散指数(PDI)的最佳ME。结果:与未配制的游离 DSF 相比,负载 DSF 的优化稳定 ME 在 B16F10 和 MCF-7 细胞系中显示出更强的溶解性、体外细胞毒性和细胞摄取能力。结论我们的研究表明,经过统计设计的负载 DSF 的优化 ME 有潜力重新用于黑色素瘤和乳腺癌的治疗。
{"title":"Quality-by-design-based microemulsion of disulfiram for repurposing in melanoma and breast cancer therapy.","authors":"Debadatta Mohapatra, Prakash Ch Senapati, Shantibhusan Senapati, Vivek Pandey, Pawan K Dubey, Sanjay Singh, Alakh N Sahu","doi":"10.1080/20415990.2024.2363136","DOIUrl":"10.1080/20415990.2024.2363136","url":null,"abstract":"<p><p><b>Aim:</b> The current study aims to develop and optimize microemulsions (ME) through Quality-by-Design (QbD) approach to improve the aqueous solubility and dissolution of poorly water-soluble drug disulfiram (DSF) for repurposing in melanoma and breast cancer therapy.<b>Materials & methods:</b> The ME was formulated using Cinnamon oil & Tween<sup>®</sup> 80, statistically optimized using a D-optimal mixture design-based QbD approach to develop the best ME with low vesicular size (Z<sub>avg</sub>) and polydispersity index (PDI).<b>Results:</b> The DSF-loaded optimized stable ME showed enhanced dissolution, <i>in-vitro</i> cytotoxicity and improved cellular uptake in B16F10 and MCF-7 cell lines compared with their unformulated free DSF.<b>Conclusion:</b> Our investigations suggested the potential of the statistically designed DSF-loaded optimized ME for repurposing melanoma and breast cancer therapy.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412148/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141470886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-09-17DOI: 10.1080/20415990.2024.2397330
Mohd Aman Mohd Ateeq, Srushti Mahajan, Brojendra Nath Saren, Mayur Aalhate, Hoshiyar Singh, Essha Chatterjee, Indrani Maji, Ujala Gupta, Anitha Sriram, Santosh Kumar Guru, Pankaj Kumar Singh
Aim: Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.Methods: I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, in-vitro release and ex-vivo permeation, cell-based assays and pharmacokinetic study.Results: DST-S-SNEDDS showed globule size and PDI of 141.53 ± 5.371 nm and 0.282 ± 0.020, respectively. DST-S-SNEDDS revealed significantly lower IC50 (1.825 μg/mL) than free DST (7.298 μg/mL) in MDA-MB-231. In-vivo pharmacokinetic study revealed 1.94-fold increment in AUC0-t for the DST-S-SNEDDS group than free DST.Conclusion: S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.
{"title":"Solid Self Nano-Emulsifying Drug Delivery System of Dasatinib: Optimization, <i>In-vitro</i>, <i>Ex-vivo</i> and <i>In-vivo</i> assessment.","authors":"Mohd Aman Mohd Ateeq, Srushti Mahajan, Brojendra Nath Saren, Mayur Aalhate, Hoshiyar Singh, Essha Chatterjee, Indrani Maji, Ujala Gupta, Anitha Sriram, Santosh Kumar Guru, Pankaj Kumar Singh","doi":"10.1080/20415990.2024.2397330","DOIUrl":"10.1080/20415990.2024.2397330","url":null,"abstract":"<p><p><b>Aim:</b> Dasatinib (DST) is an oral tyrosine kinase inhibitor with poor aqueous solubility. To outwit this issue, a solid self-nano emulsifying drug delivery system (S-SNEDDS) of DST was formulated.<b>Methods:</b> I-optimal mixture design was used for optimization of DST-loaded SNEDDS using Linalool, Cremophor RH40 and Transcutol P. S-SNEDDS underwent physicochemical characterization, <i>in-vitro</i> release and <i>ex-vivo</i> permeation, cell-based assays and pharmacokinetic study.<b>Results:</b> DST-S-SNEDDS showed globule size and PDI of 141.53 ± 5.371 nm and 0.282 ± 0.020, respectively. DST-S-SNEDDS revealed significantly lower IC<sub>50</sub> (1.825 μg/mL) than free DST (7.298 μg/mL) in MDA-MB-231. <i>In-vivo</i> pharmacokinetic study revealed 1.94-fold increment in AUC<sub>0-t</sub> for the DST-S-SNEDDS group than free DST.<b>Conclusion:</b> S-SNEDDS could be promising approach for improving bioavailability and efficacy of DST.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142296097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-05-09DOI: 10.1080/20415990.2024.2342771
Harsh P Nijhawan, Bala Prabhakar, Khushwant S Yadav
Aim: This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). Materials & methods: Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. Results: ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. Conclusion: Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.
{"title":"Central composite design augmented quality-by-design-based systematic formulation of erlotinib hydrochloride-loaded chitosan-poly (lactic-co-glycolic acid) nanoparticles.","authors":"Harsh P Nijhawan, Bala Prabhakar, Khushwant S Yadav","doi":"10.1080/20415990.2024.2342771","DOIUrl":"10.1080/20415990.2024.2342771","url":null,"abstract":"<p><p><b>Aim:</b> This study aimed to formulate erlotinib hydrochloride (ERT-HCL)-loaded chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) using Quality-by-Design (QbD) to optimize critical quality attributes (CQAs). <b>Materials & methods:</b> Quality target product profile (QTPP) and CQAs were initially established. Based on L8-Taguchi screening and risk assessments, central composite design (CCD) design was used to optimize NPs. <b>Results:</b> ERT-HCL-loaded CS-PLGA NPs had a mean particle diameter, zeta potential and entrapment efficiency of 226.50 ± 1.62 d.nm, 27.66 ± 0.64 mV and 78.93 ± 1.94 %w/w, respectively. The NPs exhibited homogenous spherical morphology and sustained release for 72 h. <b>Conclusion:</b> Using systematic QbD approach, ERT-HCL was encapsulated in CS-PLGA NPs, optimizing CQAs. These findings propel future research for improved NSCLC treatment.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11285313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140899537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-01-01Epub Date: 2024-08-05DOI: 10.1080/20415990.2024.2380244
María Sol Magi, Lucía Lopez-Vidal, Mónica Cristina García, Cinthia Carolina Stempin, Constanza Marin, Belkys Maletto, Santiago Daniel Palma, Juan Pablo Real, Alvaro Federico Jimenez-Kairuz
Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi.Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.
{"title":"Organic solvent-free benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease.","authors":"María Sol Magi, Lucía Lopez-Vidal, Mónica Cristina García, Cinthia Carolina Stempin, Constanza Marin, Belkys Maletto, Santiago Daniel Palma, Juan Pablo Real, Alvaro Federico Jimenez-Kairuz","doi":"10.1080/20415990.2024.2380244","DOIUrl":"10.1080/20415990.2024.2380244","url":null,"abstract":"<p><p><b>Aim:</b> Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.<b>Methods:</b> BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).<b>Results:</b> BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of <i>Trypanosoma cruzi</i>.<b>Conclusion:</b> BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.</p>","PeriodicalId":22959,"journal":{"name":"Therapeutic delivery","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}