Drug Delivery and Translational Research最新文献

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Exosome-based drug delivery systems for enhanced neurological therapeutics. 基于外泌体的药物输送系统,用于增强神经系统治疗。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-09-26 DOI: 10.1007/s13346-024-01710-x
Safa A Vahab, Vyshma K V, Vrinda S Kumar
{"title":"Exosome-based drug delivery systems for enhanced neurological therapeutics.","authors":"Safa A Vahab, Vyshma K V, Vrinda S Kumar","doi":"10.1007/s13346-024-01710-x","DOIUrl":"10.1007/s13346-024-01710-x","url":null,"abstract":"<p><p>Exosomes are small extracellular vesicles naturally secreted by cells into body fluids, enriched with bioactive molecules such as RNAs, proteins, and lipids. These nanosized vesicles play a crucial role in physiological and pathological processes by facilitating intercellular communication and modulating cellular responses, particularly within the central nervous system (CNS). Their ability to cross the blood-brain barrier and reflect the characteristics of their parent cells makes exosomal cargo a promising candidate for biomarkers in the early diagnosis and clinical assessment of neurological conditions. This review offers a comprehensive overview of current knowledge on the characterization of mammalian-derived exosomes, their application as drug delivery systems for neurological disorders, and ongoing clinical trials involving exosome-loaded cargo. Despite their promising attributes, a significant challenge remains the lack of standardized isolation methods, as current techniques are often complex, costly, and require sophisticated equipment, affecting the scalability and affordability of exosome-based therapies. The review highlights the engineering potential of exosomes, emphasizing their ability to be customized for targeted therapeutic delivery through surface modification or conjugation. Future advancements in addressing these challenges and leveraging the unique properties of exosomes could lead to innovative and effective therapeutic strategies in neurology.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1121-1138"},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343614","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
Nanoparticles in liposomes: a platform for increased antibiotic selectivity in multidrug resistant bacteria in respiratory tract infections. 脂质体中的纳米粒子:在呼吸道感染中提高耐多药细菌抗生素选择性的平台。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-07-24 DOI: 10.1007/s13346-024-01662-2
Nathalie E Fakhoury, Samar Mansour, Mohammad Abdel-Halim, Mostafa M Hamed, Martin Empting, Annette Boese, Brigitta Loretz, Claus-Michael Lehr, Salma N Tammam
{"title":"Nanoparticles in liposomes: a platform for increased antibiotic selectivity in multidrug resistant bacteria in respiratory tract infections.","authors":"Nathalie E Fakhoury, Samar Mansour, Mohammad Abdel-Halim, Mostafa M Hamed, Martin Empting, Annette Boese, Brigitta Loretz, Claus-Michael Lehr, Salma N Tammam","doi":"10.1007/s13346-024-01662-2","DOIUrl":"10.1007/s13346-024-01662-2","url":null,"abstract":"<p><p>Antibiotic resistance is a cause of serious illness and death, originating often from insufficient permeability into gram-negative bacteria. Nanoparticles (NP) can increase antibiotic delivery in bacterial cells, however, may as well increase internalization in mammalian cells and toxicity. In this work, NP in liposome (NP-Lip) formulations were used to enhance the selectivity of the antibiotics (3C and tobramycin) and quorum sensing inhibitor (HIPS-1635) towards Pseudomonas aeruginosa by fusing with bacterial outer membranes and reducing uptake in mammalian cells due to their larger size. Poly (lactic-co-glycolic) acid NPs were prepared using emulsion solvent evaporation and incorporated in larger liposomes. Cytotoxicity and uptake studies were conducted on two lung cell lines, Calu-3 and H460. NP-Lip showed lower toxicity and uptake in both cell lines. Then formulations were investigated for suitability for oral inhalation. The deposition of NP and NP-Lip in the lungs was assessed by next generation impactor and corresponded to 75% and 45% deposition in the terminal bronchi and the alveoli respectively. Colloidal stability and mucus-interaction studies were conducted. NP-Lip showed higher diffusion through mucus compared to NPs with the use of nanoparticle tracking analyzer. Moreover, the permeation of delivery systems across a liquid-liquid interface epithelial barrier model of Calu-3 cells indicated that NP-Lip could cause less systemic toxicity upon in-vivo like administration by aerosol deposition. Monoculture and Pseudomonas aeruginosa biofilm with Calu-3 cells co-culture experiments were conducted, NP-Lip achieved highest toxicity towards bacterial biofilms and least toxicity % of the Calu-3 cells. Therefore, the NP- liposomal platform offers a promising approach for enhancing antibiotic selectivity and treating pulmonary infections.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1193-1209"},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141757754","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
Dual acting oxaliplatin (IV) prodrug loaded albumin nanoparticles for safer synergistic anticancer action against triple negative breast cancer.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-11 DOI: 10.1007/s13346-025-01833-9
Kshitija Abhang, Sayali Dighe, Oly Katari, Vivek Yadav, Sanyog Jain
{"title":"Dual acting oxaliplatin (IV) prodrug loaded albumin nanoparticles for safer synergistic anticancer action against triple negative breast cancer.","authors":"Kshitija Abhang, Sayali Dighe, Oly Katari, Vivek Yadav, Sanyog Jain","doi":"10.1007/s13346-025-01833-9","DOIUrl":"https://doi.org/10.1007/s13346-025-01833-9","url":null,"abstract":"<p><p>Owing to faulty DNA damage repair system, triple negative breast cancer (TNBC) exhibits high susceptibility towards DNA damaging drugs such as platinum compounds e.g., oxaliplatin. Nevertheless, the clinical utility of oxaliplatin (OXA) has been constrained due to chemoresistance and chronic toxicities. Hence, to confer systemic inertness, tumor specific delivery, and multifaceted action, a octahedral OXA-CBL prodrug was synthesized using chlorambucil (CBL) as an axial ligand. The combination of OXA and CBL exhibited synergistic anti-cancer action in TNBC cell lines. Further, to potentiate the cellular internalization, targeting efficiency, and in-vivo performance, the synthesized prodrug was loaded into bovine serum albumin nanoparticles (OXA-CBL/BSA-NPs). The prepared nanoparticles had optimal particle size < 200 nm and high drug loading (∼ 5.863 ± 0.16%). As relative to free conjugate, the nanoparticles exhibited amplified cellular internalization and reduced the IC<sub>50</sub> in 4T1 (∼ 1.38-fold) and MDA-MB-231 (∼ 1.43-fold) cell line. The anti-cancer study in 4T1-based TNBC model in BALB/c mice demonstrated significantly higher tumor inhibition rate, and reduced tumor burden in OXA-CBL/BSA-NPs treated group. Toxicity assessment revealed no signs of hepato- and/or renal toxicity. Also, nanoparticles exhibited sufficient compatibility with erythrocytes. Overall, delivery of OXA-CBL via virtue of albumin nanoparticles presents safer and efficacious approach to combat TNBC.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603556","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
Effects of beta and gamma radiation sterilization on growth factor-loaded nanoparticles: an innovative approach for osteoarticular disorders treatment.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-11 DOI: 10.1007/s13346-025-01829-5
Jorge Ordoyo-Pascual, Sandra Ruiz-Alonso, Idoia Gallego, Laura Saenz-Del-Burgo, Jose Luis Pedraz
{"title":"Effects of beta and gamma radiation sterilization on growth factor-loaded nanoparticles: an innovative approach for osteoarticular disorders treatment.","authors":"Jorge Ordoyo-Pascual, Sandra Ruiz-Alonso, Idoia Gallego, Laura Saenz-Del-Burgo, Jose Luis Pedraz","doi":"10.1007/s13346-025-01829-5","DOIUrl":"https://doi.org/10.1007/s13346-025-01829-5","url":null,"abstract":"<p><p>The prevalence of various diseases, including osteoarticular conditions, is increasing as the world's population ages. These disorders lead to degeneration of bones and joints, diminishing the quality of life of the geriatric population and imposing a significant economic burden on healthcare systems. The aim of the present study is to sterilize nanostructured lipid carriers (NLCs) loaded with vascular endothelial growth factor 165 (VEGF165) and platelet-derived growth factorBB (PDGF-BB) without compromising their properties to improve osteoarticular disease prognosis. Therefore, two methods of sterilization using ionizing radiation - beta radiation and gamma radiation - and two different doses - 12 kGy and 25 kGy - were investigated. Subsequently, the study evaluated whether the sterilization process had any effect on the nanoparticles and encapsulated growth factors by assessing their physicochemical properties, toxicity, release profiles and bioactivity. The treatment with 12 kGy of beta radiation successfully sterilized the batch of nanoparticles without inducing any changes in the physicochemical properties. In addition, the release profile of VEGF165 remained unchanged, although a slight decrease was observed in the case of PDGF-BB. The biological activity of the growth factors showed a slight decrease, with the most effective concentrations being 5 ng/mL for VEGF165 and 50 ng/mL for PDGF-BB. Taken together, these findings suggest that the nanoparticles loaded with VEGF165 and PDGF-BB can be successfully sterilized while retaining both their properties and biological activity. These nanoparticles may offer a promising new approach for the treatment of osteoarticular diseases by enhancing vascularization and promoting cellular proliferation in the affected tissue.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603818","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
Simvastatin loaded surface-decorated 3D-dendritic mesoporous silica nanoparticles for enhanced antihyperlipidemic activity: in vitro and in vivo appraisal.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-11 DOI: 10.1007/s13346-025-01825-9
Abdulsalam M Kassem, Elsaied H Barakat, Maged K Elsayad, Sherif E Emam, Tarek M Ibrahim, Ayman Salama, Mohammed Elmowafy, Nabil K Alruwaili, Omar Awad Alsaidan, Mohamed A Abdelgawad
{"title":"Simvastatin loaded surface-decorated 3D-dendritic mesoporous silica nanoparticles for enhanced antihyperlipidemic activity: in vitro and in vivo appraisal.","authors":"Abdulsalam M Kassem, Elsaied H Barakat, Maged K Elsayad, Sherif E Emam, Tarek M Ibrahim, Ayman Salama, Mohammed Elmowafy, Nabil K Alruwaili, Omar Awad Alsaidan, Mohamed A Abdelgawad","doi":"10.1007/s13346-025-01825-9","DOIUrl":"https://doi.org/10.1007/s13346-025-01825-9","url":null,"abstract":"<p><p>Simvastatin is a potent statin with antioxidant and anti-inflammatory characteristics, often used to treat hyperlipidemia and related cardiovascular disorders. Nonetheless, its therapeutic advantages are limited by poor water solubility and substantial degradation by CYP3A4 enzymes. This research aimed to improve simvastatin's physicochemical characteristics and therapeutic effectiveness by developing 3D-dendritic mesoporous silica nanoparticles as nanocarriers. Dendritic silica nanoparticles were manufactured using a one-pot biphase stratification process and then surface-modified with aminopropyl groups to enhance drug loading and release characteristics. The optimization of loading parameters, such as solvent type, drug-to-carrier ratio, and loading duration, produced dendritic spherical nanoparticles with a uniform size (< 200 nm), a zeta potential of + 21 mV, and a substantial drug loading capacity (> 20%). Characterization verified the conversion of crystalline simvastatin into an amorphous state, promoting improved saturation solubility and demonstrating sustained release via a Fickian diffusion mechanism. In vivo assessments revealed enhanced antihyperlipidemic, antioxidant properties, and considerable protection against oxidative damage in a poloxamer-407-induced hyperlipidemia model. Histological evaluations of liver and aorta tissues demonstrated almost normal morphology, highlighting the safety and usefulness of the nanoparticles. These results emphasized the potential of aminated dendritic silica nanoparticles as an effective platform for enhancing simvastatin therapeutic efficacy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143603824","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
Microemulsion-based formulation of enterocin CC2: a novel antimicrobial solution targeting Streptococcus mutans.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-08 DOI: 10.1007/s13346-025-01823-x
Zhang Jin Ng, Choon Fu Goh, Ana Masara Ahmad Mokhtar, Rozi Nuraika Binti Ramli, Chee Keong Lee, Joo Shun Tan
{"title":"Microemulsion-based formulation of enterocin CC2: a novel antimicrobial solution targeting Streptococcus mutans.","authors":"Zhang Jin Ng, Choon Fu Goh, Ana Masara Ahmad Mokhtar, Rozi Nuraika Binti Ramli, Chee Keong Lee, Joo Shun Tan","doi":"10.1007/s13346-025-01823-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01823-x","url":null,"abstract":"<p><p>Dental caries, driven predominantly by Streptococcus mutans, remains a significant global challenge. Conventional treatments often fall short due to antimicrobial resistance and limited efficacy. Enterocin CC2, a potent bacteriocin, offers a promising alternative but is hindered by stability and delivery challenges. This study pioneers the development of a cutting-edge microemulsion designed to enhance the stability, bioavailability, and antimicrobial potency of enterocin CC2 against S. mutans. A comprehensive screening of 124 formulations was conducted, evaluating thermodynamic stability, cytotoxicity, and antioxidant potential. The optimized formulation underwent rigorous analysis for physicochemical properties, antimicrobial activity, and long-term stability under varied storage conditions. The innovative microemulsion formulation, incorporating 0.5 mg/mL enterocin CC2, 0.5% surfactant blend (Tween 80 + PEG 400, 1:1), and 0.5% oil, demonstrated micro-sized droplets (88.50-92.10 nm), exceptional thermodynamic stability, and robust antimicrobial efficacy. Remarkably, it reduced the time to eradicate S. mutans UKMCC 1019 from 8 h (unformulated) to 5 h, outperforming 0.2% w/v chlorhexidine and 0.5 mg/mL nisin. Stability tests confirmed consistent performance in pH, viscosity, and antimicrobial activity for up to six weeks across various temperatures, with no detectable cytotoxicity. This study introduces a groundbreaking microemulsion formulation that redefines antimicrobial therapy for S. mutans. By leveraging the enhanced stability and rapid action of enterocin CC2, this innovation offers a transformative approach to oral health management, paving the way for next-generation antimicrobial solutions.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585106","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
Local delivery of an adenosine receptor agonist reduces inflammation associated with contact hypersensitivity.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-08 DOI: 10.1007/s13346-025-01831-x
Elizabeth R Bentley, Stacia Subick, Jake Doran, Julie Kobyra, Stephen C Balmert, Steven R Little
{"title":"Local delivery of an adenosine receptor agonist reduces inflammation associated with contact hypersensitivity.","authors":"Elizabeth R Bentley, Stacia Subick, Jake Doran, Julie Kobyra, Stephen C Balmert, Steven R Little","doi":"10.1007/s13346-025-01831-x","DOIUrl":"https://doi.org/10.1007/s13346-025-01831-x","url":null,"abstract":"<p><p>Allergic contact dermatitis (ACD), a T-cell mediated inflammatory skin condition, is prompted by multiple, subsequent exposures to contact allergens (e.g., nickel). Current treatment approaches for ACD include repeated topical application or systemic delivery of immunosuppressants. These treatment strategies have many limitations, including non-specific mechanism of actions and the occurrence of side effects due to their delivery method. For this reason, we developed a novel therapeutic approach that is based upon adenosine (Ado) receptor signaling, a known anti-inflammatory pathway. Specifically, we developed a polymer microparticle-based controlled release system capable of presenting IBMECA (IBMECA-MPs), an Ado receptor agonist, to the local environment. In this study, we first sought to study the immunosuppressive effects of IBMECA on immune cells implicated in the pathogenesis of ACD (e.g., dendritic cells) in vitro. Subsequently, we examined the effects of enhancing adenosine signaling in contact hypersensitivity (CHS), an in vivo model of ACD, through local administration of IBMECA-MPs. We observed that IBMECA-MPs were capable of reducing the inflammatory response associated with CHS by reducing maturation markers of antigen-presenting cells, altering cytokine secretion, and reducing relative frequencies of effector T cell populations. To our knowledge, this is the first demonstration of therapeutic efficacy of IBMECA in CHS, as well as the first proof-of-principle demonstration of IBMECA application in the context of a local drug delivery system. Ultimately, this delivery system has the potential to be adapted for use in other T-cell mediated inflammatory conditions (e.g., transplant rejection), suggesting broader implications of this study.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585100","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
Harnessing the composition of lipid nanoparticles to selectively deliver mRNA to splenic immune cells for anticancer vaccination.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-07 DOI: 10.1007/s13346-025-01824-w
Mahmoud A Younis, Yusuke Sato, Yaser H A Elewa, Hideyoshi Harashima
{"title":"Harnessing the composition of lipid nanoparticles to selectively deliver mRNA to splenic immune cells for anticancer vaccination.","authors":"Mahmoud A Younis, Yusuke Sato, Yaser H A Elewa, Hideyoshi Harashima","doi":"10.1007/s13346-025-01824-w","DOIUrl":"https://doi.org/10.1007/s13346-025-01824-w","url":null,"abstract":"<p><p>Herein, we report a design for lipid nanoparticles (LNPs) that specifically delivers mRNA to splenic immune cells post intravenous administration for potential anticancer vaccination applications. A diverse library of ionizable lipids was screened in vivo, in combination with various helper lipids, where the composition of LNPs was tweaked to control their in vivo performance. The biodistribution of the LNPs was then investigated at both organ and sub-organ levels. Subsequently, the LNPs were recruited to deliver an anticancer mRNA-based vaccine to mice. The in vivo tropism of the LNPs was dramatically affected by the chemical structure of the ionizable lipids in question, where a model lipid, CL15H6, was recognized as displaying high affinity for the spleen. Further optimization of the composition of the LNPs enabled highly efficient and spleen-selective mRNA delivery, where the optimized CL15H6 LNPs demonstrated a high capacity for homing to splenic antigen-presenting cells (APCs). Furthermore, loading the LNPs with a low dose of ovalbumin-encoding mRNA (mOVA), as a model antigen, protected the mice against OVA-expressing tumor challenges and suppressed the tumor growth in tumor-bearing mice by ~ 75%, which was superior to the results of a clinically-relevant formulation. The CL15H6 LNPs proved to be biosafe upon either acute dose escalation or repeated administrations. The novel and scalable platform reported herein is promising for clinical translation as a neoantigen vaccine.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143585089","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
Nano-formulated curcumin uptake and biodistribution in the fetal growth restricted newborn piglet brain.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-07 DOI: 10.1007/s13346-025-01830-y
Nuo Xu, Julie Wixey, Kirat Chand, Megan Wong, Elizabeth Nance
{"title":"Nano-formulated curcumin uptake and biodistribution in the fetal growth restricted newborn piglet brain.","authors":"Nuo Xu, Julie Wixey, Kirat Chand, Megan Wong, Elizabeth Nance","doi":"10.1007/s13346-025-01830-y","DOIUrl":"https://doi.org/10.1007/s13346-025-01830-y","url":null,"abstract":"<p><p>Fetal growth restriction (FGR) affects 5% to 10% of all pregnancies in developed countries and is the second most leading cause of perinatal mortality and morbidity. Life-long consequences of FGR range from learning and behavioral issues to cerebral palsy. To support the newborn brain following FGR, timely and accessible neuroprotection strategies are needed. Curcumin-loaded polymeric nanoparticles, which have been widely explored for the treatment of cancer, neurological disorders, and bacterial infections, have the potential to prevent and mitigate pathogenic inflammatory processes in the FGR brain. Curcumin is a hydrophobic molecule with poor aqueous solubility and therefore has been incorporated into nanoparticles to improve solubility and delivery. However, curcumin loading in many nanoparticles can be limited to 10% by weight or lower. Here, we first optimize the formulation process of curcumin-loaded polymeric nanoparticles to find a tunable, reproducible, and stable formulation with high curcumin loading and encapsulation efficiency. We establish a curcumin formulation with 39% curcumin loading and > 95% curcumin encapsulation efficiency. Using this formulation, we assessed the biodistribution of polymeric nanoparticles in FGR piglets and normally grown (NG) piglets following different administration routes and evaluated brain cellular uptake. We show a significant amount of nanoparticle accumulation in the brain parenchyma of neonatal piglets as early as 4 h after intranasal administration. Nanoparticles colocalized in microglia, a therapeutic target of interest in FGR brain injury. This study demonstrates the potential of curcumin-loaded nanoparticles to treat neuroinflammation associated with FGR in the newborn.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572519","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
Improvement of coronary microcirculation in acute myocardial ischemia rats using a nanoscale carrier SiO2@PEG loaded with Nicorandil.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-07 DOI: 10.1007/s13346-025-01820-0
Rui Wang, Yujing Mo, Yingcong Liang, Yuanhui Liu, Zhongchan Sun, Wenting Shang, Ling Xue
{"title":"Improvement of coronary microcirculation in acute myocardial ischemia rats using a nanoscale carrier SiO<sub>2</sub>@PEG loaded with Nicorandil.","authors":"Rui Wang, Yujing Mo, Yingcong Liang, Yuanhui Liu, Zhongchan Sun, Wenting Shang, Ling Xue","doi":"10.1007/s13346-025-01820-0","DOIUrl":"https://doi.org/10.1007/s13346-025-01820-0","url":null,"abstract":"<p><p>Coronary microcirculatory dysfunction, affecting over half of acute myocardial infarction (AMI) patients, correlates significantly with AMI prognosis. Nicorandil is an effective drug that markedly improves coronary microcirculation, but current clinical formulations of Nicorandil exhibit a relatively short half-life and lack cardiac selectivity. We formulated and synthesized a variety of mesoporous silica nanoparticles (MSNs) as a drug carrier for loading and delivering Nicorandil. We performed PEG modification on MSNs to enhance their biocompatibility. The SiO<sub>2</sub>@PEG showed good serum stability, maintained a uniform spherical structure with a particle size distribution centered within 200 nm and exhibits good dispersibility. SiO<sub>2</sub>@PEG-Nicorandil showed no significant impact on AC 16 cells' viability at concentrations up to 50 µg/mL. SiO<sub>2</sub>@PEG-Nicorandil significantly enhanced the viability of AC16 cells under oxidative stress conditions, while concurrently reducing intracellular levels of reactive oxygen species (ROS) and Ca²⁺. For the rat coronary microvascular dysfunction model, the SiO<sub>2</sub>@PEG-Nicorandil group demonstrated a greater decrease in thrombus formation and the expression of inflammatory cytokines, outperforming the Nicorandil group. In vivo imaging revealed that within one hour post-injection of SiO<sub>2</sub>@PEG-Nicorandil-CY7, a notable increase in CY7 fluorescence intensity was observed in the cardiac region compared to surrounding tissues. Drug concentration measurements demonstrated that Nicorandil maintained a stable concentration in cardiac blood at 48 h in the SiO<sub>2</sub>@PEG-Nicorandil group. Taken together, SiO<sub>2</sub>@PEG-Nicorandil had exhibited superior cardiac-targeting capabilities and sustained-release properties. Within a specific concentration range, it demonstrated enhanced therapeutic effects in the treatment of coronary microcirculation disorders in rats when compared to conventional Nicorandil formulations.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572518","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
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