Drug Delivery and Translational Research最新文献

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The penetration efficiency of a dissolved model drug into hair follicles depends on the concentration of added nanoparticles. 溶解的模型药物对毛囊的渗透效率取决于添加的纳米颗粒的浓度。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-10-04 DOI: 10.1007/s13346-024-01718-3
Loris Busch, Darya Asadzadeh, Anna Lena Klein, Phuvamin Suriyaamporn, Mont Kumpugdee Vollrath, Cornelia M Keck, Martina C Meinke
{"title":"The penetration efficiency of a dissolved model drug into hair follicles depends on the concentration of added nanoparticles.","authors":"Loris Busch, Darya Asadzadeh, Anna Lena Klein, Phuvamin Suriyaamporn, Mont Kumpugdee Vollrath, Cornelia M Keck, Martina C Meinke","doi":"10.1007/s13346-024-01718-3","DOIUrl":"10.1007/s13346-024-01718-3","url":null,"abstract":"<p><p>Hair follicles have recently emerged as promising drug delivery targets and gates for skin penetration. The so-called ratchet effect, which is based on an interaction between the hair shaft surface, the intrafollicular stratum corneum and nanoparticles, has proven to be very effective for the transport of active ingredients. Especially the nanoparticle-assisted decolonization of hair follicles constitutes an interesting new area of application. In a recently published work it was shown that small molecules as well as macromolecules solved in an outer phase of a formulation can be transported into the deeper parts of the hair follicles by adding nanoparticles to the formulation. In this case the nanoparticles constitute an entity independent of the drug and the transport is hypothesized to be based on an adhesion effect. In the present work, we focused on the impact of the particle concentration in the formulation on the transport efficiency of the model drug fluorescein sodium into hair follicles utilizing an ex vivo porcine skin model. It was observed that a particle concentration of 4% significantly enhances the transport efficiency of fluorescein as compared to 2% particle concentration. Doubling the concentration to 8% did not significantly increase the penetration depth. The effect evolved more efficiently when using 4 Hz circular motion massage as compared to 100 Hz oscillating massage. These results deliver interesting information on the optimal formulation as well as application parameters for a future application in clinical studies for e.g. skin antisepsis purposes.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1444-1452"},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371295","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
Flexible surface acoustic wave technology for enhancing transdermal drug delivery. 用于加强透皮给药的柔性表面声波技术。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-08-06 DOI: 10.1007/s13346-024-01682-y
Jikai Zhang, Duygu Bahar, Hui Ling Ong, Peter Arnold, Meng Zhang, Yunhong Jiang, Ran Tao, Luke Haworth, Xin Yang, Chelsea Brain, Mohammad Rahmati, Hamdi Torun, Qiang Wu, Jingting Luo, Yong-Qing Fu
{"title":"Flexible surface acoustic wave technology for enhancing transdermal drug delivery.","authors":"Jikai Zhang, Duygu Bahar, Hui Ling Ong, Peter Arnold, Meng Zhang, Yunhong Jiang, Ran Tao, Luke Haworth, Xin Yang, Chelsea Brain, Mohammad Rahmati, Hamdi Torun, Qiang Wu, Jingting Luo, Yong-Qing Fu","doi":"10.1007/s13346-024-01682-y","DOIUrl":"10.1007/s13346-024-01682-y","url":null,"abstract":"<p><p>Transdermal drug delivery provides therapeutic benefits over enteric or injection delivery because its transdermal routes provide more consistent concentrations of drug and avoid issues of drugs affecting kidneys and liver functions. Many technologies have been evaluated to enhance drug delivery through the relatively impervious epidermal layer of the skin. However, precise delivery of large hydrophilic molecules is still a great challenge even though microneedles or other energized (such as electrical, thermal, or ultrasonic) patches have been used, which are often difficult to be integrated into small wearable devices. This study developed a flexible surface acoustic wave (SAW) patch platform to facilitate transdermal delivery of macromolecules with fluorescein isothiocyanates up to 2000 kDa. Two surrogates of human skin were used to evaluate SAW based energized devices, i.e., delivering dextran through agarose gels and across stratum corneum of pig skin into the epidermis. Results showed that the 2000 kDa fluorescent molecules have been delivered up to 1.1 mm in agarose gel, and the fluorescent molecules from 4 to 2000 kDa have been delivered up to 100 µm and 25 µm in porcine skin tissue, respectively. Mechanical agitation, localised streaming, and acousto-thermal effect generated on the skin surface were identified as the main mechanisms for promoting drug transdermal transportation, although micro/nanoscale acoustic cavitation induced by SAWs could also have its contribution. SAW enhanced transdermal drug delivery is dependent on the combined effects of wave frequency and intensity, duration of applied acoustic waves, temperature, and drug molecules molecular weights.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1363-1375"},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11870993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897096","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
PBPK model of pegylated liposomal doxorubicin to simultaneously predict the concentration-time profile of encapsulated and free doxorubicin in tissues. 建立多柔比星聚乙二醇脂质体的 PBPK 模型,以同时预测组织中包裹的多柔比星和游离的多柔比星的浓度-时间曲线。
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-04-01 Epub Date: 2024-08-05 DOI: 10.1007/s13346-024-01680-0
Xuewei Cao, Kejun Li, Jingyu Wang, Xiaoqian Xie, Le Sun
{"title":"PBPK model of pegylated liposomal doxorubicin to simultaneously predict the concentration-time profile of encapsulated and free doxorubicin in tissues.","authors":"Xuewei Cao, Kejun Li, Jingyu Wang, Xiaoqian Xie, Le Sun","doi":"10.1007/s13346-024-01680-0","DOIUrl":"10.1007/s13346-024-01680-0","url":null,"abstract":"<p><p>The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model to predict the concentrations of encapsulated and free doxorubicin in plasma and tissues in mice after intravenous injection of PEGylated liposomes (Doxil<sup>®</sup>). The PBPK model used in this study contains liposomes and free doxorubicin disposition components. The free doxorubicin disposition component was used to simulate the disposition of free doxorubicin produced by mononuclear phagocyte system (MPS)-degrading liposomes. The liver, spleen, kidneys, and lungs contain an additional MPS subcompartment. These compartments are interconnected through blood and lymphatic circulation. The model was validated strictly by four doses of external observed plasma and tissue concentration-time profiles. The fold error (FE) values were almost all within threefold. The sensitivity analysis revealed that the MPS-related parameters greatly influenced the model. The predicted in vivo distribution characteristics of the doxorubicin liposomes and doxorubicin solution were consistent with the observed values. The PBPK model was established based on the physiological mechanism and parameters of practical significance that can be measured in vitro. Thus, it can be used to study the pharmacokinetic properties of liposomes. This study also provides a reference for the establishment of liposome PBPK model.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":"1342-1362"},"PeriodicalIF":5.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141893127","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
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
Peptide-functionalized nanoparticles for brain-targeted therapeutics.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-31 DOI: 10.1007/s13346-025-01840-w
Sophia Tang, Emily L Han, Michael J Mitchell
{"title":"Peptide-functionalized nanoparticles for brain-targeted therapeutics.","authors":"Sophia Tang, Emily L Han, Michael J Mitchell","doi":"10.1007/s13346-025-01840-w","DOIUrl":"https://doi.org/10.1007/s13346-025-01840-w","url":null,"abstract":"<p><p>Despite the rapid development of nanoparticle (NP)-based drug delivery systems, intravenous delivery of drugs to the brain remains a major challenge due to various biological barriers. To achieve therapeutic effects, NP-encapsulated drugs must avoid accumulation in off-target organs and selectively deliver to the brain, successfully cross the blood-brain barrier (BBB), and reach the target cells in the brain. Conjugating receptor-specific ligands to the surface of NPs is a promising technique for engineering NPs to overcome these barriers. Specifically, peptides as brain-targeting ligands have been of increasing interest given their ease of synthesis, low cytotoxicity, and strong affinity to target proteins. The success of peptides as targeting ligands is largely due to the diverse strategies of designing and modifying peptides with favorable properties, including membrane permeability and multi-receptor targeting. Here, we review the design and implementation of peptide-functionalized NP systems for neurological disease applications. We also explore advances in rational peptide design strategies for brain targeting, including using generative deep-learning models to computationally design new peptides.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751599","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
Thermostability of tetanus toxoid vaccine encapsulated in metal-organic frameworks.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-28 DOI: 10.1007/s13346-025-01838-4
Rohan Murty, Krista S Walton, Mark R Prausnitz
{"title":"Thermostability of tetanus toxoid vaccine encapsulated in metal-organic frameworks.","authors":"Rohan Murty, Krista S Walton, Mark R Prausnitz","doi":"10.1007/s13346-025-01838-4","DOIUrl":"https://doi.org/10.1007/s13346-025-01838-4","url":null,"abstract":"<p><p>Most vaccines require refrigerated transport and storage, which is costly, challenging in low-resource settings, and results in the loss of up to 50% of vaccines globally due to \"cold-chain\" failures. Here, tetanus toxoid vaccine (TT) was thermostabilized by encapsulation within a metal-organic framework (MOF), zeolitic imidazolate framework-8 (TT@ZIF-8). Its physicochemical properties were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and confocal microscopy. Unencapsulated TT fell below the 80% activity threshold within 4 days at 40˚C and 60˚C according to immunoassay analysis. Aqueous suspensions of TT@ZIF-8 also declined below 80% activity within a week at both temperatures, likely due to MOF degradation in water. Dried TT@ZIF-8 performed better, retaining 80% stability for 33 days at 40˚C and 22 days at 60˚C. When TT@ZIF-8 was suspended in a non-aqueous mixture of propylene glycol and ethanol, it remained 80% stable for approximately 4 months at 40˚C and 2.5 months at 60˚C. Arrhenius modeling predicted this formulation may qualify for \"controlled temperature chain\" designation, allowing partial vaccine removal from the cold chain. These studies suggest that MOF encapsulation of vaccines like TT can enable dramatic improvements in vaccine stability during storage without refrigeration.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742641","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
Optimized mucus adhesion and penetration of lipid-polymer nanoparticles enables effective nose-to-brain delivery of perillyl alcohol for glioblastoma therapy.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-25 DOI: 10.1007/s13346-025-01837-5
Edilson Ribeiro de Oliveira Junior, Jonathan Matheus Silva, Mariana Arraes Salomão, Nathalia Correa de Almeida Oliveira, Carla Santos de Freitas, Natália Noronha Ferreira, Natalia Sanchez Moreno, Camila Fernanda Rodero, Daniel Graziani, Valtencir Zucolotto, Sebastião Antônio Mendanha, Eliana Martins Lima
{"title":"Optimized mucus adhesion and penetration of lipid-polymer nanoparticles enables effective nose-to-brain delivery of perillyl alcohol for glioblastoma therapy.","authors":"Edilson Ribeiro de Oliveira Junior, Jonathan Matheus Silva, Mariana Arraes Salomão, Nathalia Correa de Almeida Oliveira, Carla Santos de Freitas, Natália Noronha Ferreira, Natalia Sanchez Moreno, Camila Fernanda Rodero, Daniel Graziani, Valtencir Zucolotto, Sebastião Antônio Mendanha, Eliana Martins Lima","doi":"10.1007/s13346-025-01837-5","DOIUrl":"https://doi.org/10.1007/s13346-025-01837-5","url":null,"abstract":"<p><p>The delivery of drugs directly from the nose to the brain has been explored for the treatment of neurological diseases, such as glioblastoma, by overcoming the blood-brain barrier. Nanocarriers have demonstrated outstanding ability to enhance drug bioavailability in the brain, following intranasal administration. However, the performance of these nanosystems may be hindered by inadequate interactions with the nasal mucosa, limiting their effectiveness in reaching the olfactory region, and consequently, the translocation of particles to the brain. Here, we designed hybrid lipid-polymer nanoparticles (LPNP), containing the cationic lipid DOTAP and the triblock copolymer Pluronic<sup>®</sup> F127 to combine the mucoadhesiveness and mucus-penetrating properties. Perillyl alcohol (POH), a molecule currently under clinical trials against glioblastoma, via intranasal route, was entrapped in the nanoparticles. LPNP-POH exhibited a balanced profile of mucus adhesion and penetration, suggesting that the formulation may enhance mucosal retention while maintaining effective mucus diffusivity. In vivo evaluations displayed higher translocation of LPNP-POH from the nasal cavity to the brain. LPNP-POH resulted in a 2.5-fold increase in the concentration of perillyl acid (a primary metabolite of POH) in the cerebral tissue compared to the free drug. In vitro assays demonstrated that LPNP-POH increased the cytotoxicity and reduced the tumor growth of U87MG glioma cells. These results highlighted that the engineered formulation, with optimized mucoadhesiveness and mucus penetration properties, improved nose-to-brain delivery of POH, offering a promising potential for glioblastoma therapy.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709153","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
Activated carbon-chitosan hydrogel dressing loaded with LL37 microspheres for the treatment of infected wounds: In vivo antimicrobial and antitoxin assessment.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-22 DOI: 10.1007/s13346-025-01835-7
Bee-Yee Lim, Fazren Azmi, Shiow-Fern Ng
{"title":"Activated carbon-chitosan hydrogel dressing loaded with LL37 microspheres for the treatment of infected wounds: In vivo antimicrobial and antitoxin assessment.","authors":"Bee-Yee Lim, Fazren Azmi, Shiow-Fern Ng","doi":"10.1007/s13346-025-01835-7","DOIUrl":"https://doi.org/10.1007/s13346-025-01835-7","url":null,"abstract":"<p><p>Wound healing is a complex process which is crucial for recovery. Delayed wound healing which is caused by the presence of pathogens has posed significant clinical implications affecting millions of patients globally. Wounds infection caused by Pseudomonas aeruginosa present significant challenges due to their resistance to multiple antimicrobial drugs. The Gram-negative bacteria secretes endotoxin lipopolysaccharide (LPS), which impede wound healing and may lead to severe complications, including life-threatening sepsis. Previously, our laboratory has successfully developed a new hydrogel containing a synthetic antimicrobial peptide as an alternative therapy to conventional antibiotics. This hydrogel contains LL37 microspheres embedded into activated carbon-chitosan hydrogel (LL37-AC-CS). LL37-AC-CS has shown desirable physicochemical properties as well as promising antimicrobial and antitoxin activities in vitro. This current study has two main objectives. The first is to evaluate the in vivo antimicrobial efficacy of LL37-AC-CS hydrogel in full-thickness rat wounds infected with P. aeruginosa. The second objective is to investigate the antitoxin efficacy on the rat wound models treated with E. coli endotoxins LPS. The wound healing efficacy was assessed in terms of the macroscopic appearance, wound contraction rate, histology, and wound tissue biochemical markers. As a result, the LL37-AC-CS hydrogel exhibited remarkable antimicrobial and antitoxin efficacy as compared to the controls. The wound healing efficacy was evident in increased wound closure rate and decrease in bacterial bioburden, and favourable changes in wound healing biomarkers namely the myeloperoxidase, interleukin-6 and tumour necrosis factor α. The elevation of hydroxyproline levels in the LPS-treated wound model indicates there was collagen synthesis. In conclusion, the results presented in this study have significantly enhanced our comprehension of the LL37-AC-CS hydrogel's potential in wound healing. Specifically, the research highlights its effectiveness in eliminating endotoxins and preventing bacterial growth.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691465","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
Combination of mannoside and phenylboronic acid polycaprolactone polymers for doxorubicin-encapsulated polymersome nanomedicine targeting MDA-MB-231 cancer cells.
IF 5.7 3区 医学
Drug Delivery and Translational Research Pub Date : 2025-03-22 DOI: 10.1007/s13346-025-01836-6
Yung-Hsin Huang, Govindan Sivakumar, Rajiv Kamaraj, Kai Yi Lim, Yu-Xuan Chen, Cheng-Han Liu, Yi-Cheng Wang, Hsuan-Ying Chen, Tuck Whye Wong, Yuan Wen Hau, Chian-Hui Lai
{"title":"Combination of mannoside and phenylboronic acid polycaprolactone polymers for doxorubicin-encapsulated polymersome nanomedicine targeting MDA-MB-231 cancer cells.","authors":"Yung-Hsin Huang, Govindan Sivakumar, Rajiv Kamaraj, Kai Yi Lim, Yu-Xuan Chen, Cheng-Han Liu, Yi-Cheng Wang, Hsuan-Ying Chen, Tuck Whye Wong, Yuan Wen Hau, Chian-Hui Lai","doi":"10.1007/s13346-025-01836-6","DOIUrl":"https://doi.org/10.1007/s13346-025-01836-6","url":null,"abstract":"<p><p>This study aims to create glyco-based nanoparticles (NPs) with high drug-loading capability for targeted cancer treatment, specifically against MDA-MB-231 breast cancer cells. Traditional NPs have faced limitations due to low drug-loading capacities, leading to suboptimal therapeutic effectiveness and significant side effects. To overcome these limitations, DOX@pB-pM NP were synthesized using a self-assembly combination method of two poly(ε-caprolactone) (PCL) based polymers, mannoside-b-PCL (pM) and phenylboronic acid (PBA)-mPEG-t-PCL (pB). The pM polymer synthesis includes a Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAc) reaction. DOX@pB-pM NP's mannose moiety is specifically engineered to target MDA-MB-231 cells, while the core of the NPs is made of hydrophobic, biodegradable polyester PCL. The functions of mPEG and PBA in the pB tri-block copolymer are to enhance biocompatibility and drug-loading efficiency, respectively. Additionally, mPEG can reduce nonspecific interactions. The PBA on the pB introduces a hydrophobic segment to the copolymer, which can improve the interaction with water-insoluble drugs, doxorubicin (DOX). The PBA moiety can also provide additional functionality, such as pH-responsive and H<sub>2</sub>O<sub>2</sub>-responsive drug release, which is particularly useful in targeting the tumor's acidic and oxidative microenvironment. The PBA groups convert them to boronic acid and 4-(hydroxymethyl) phenol, which destroys the NP core and causes DOX release, resulting in cell death. The in vitro release profile of DOX from the DOX@pB-pM NPs was evaluated under various conditions, including different pH levels and the presence or absence of H<sub>2</sub>O<sub>2</sub>, to simulate the acidic tumor microenvironment. The cytotoxicity of the DOX@pB-pM NPs was assessed using the MTT assay, which demonstrated significant inhibition of MDA-MB-231 breast cancer cell growth by DOX@pB-pM NPs. By combining mannose for the targeting of MDA-MB-231 breast cancer cells and fine-tuning the ratio of pM and pB polymers, the NPs showed good therapeutic efficacy. Importantly, pB-pM NPs displayed good biocompatibility, with no significant effect on cell survival even at high concentrations, indicating their potential as safe drug carriers. These data show that DOX@pB-pM NPs can potentially improve cancer therapeutic efficacy and safety.</p>","PeriodicalId":11357,"journal":{"name":"Drug Delivery and Translational Research","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691466","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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