Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-07-11DOI: 10.1080/10717544.2024.2372279
Katarzyna Krzeminska, Malgorzata Sznitowska, Magdalena Wroblewska, Eliza Wolska, Katarzyna Winnicka
{"title":"Suspensions of antibiotics in self-emulsifying oils as a novel approach to formulate eye drops with substances which undergo hydrolysis in aqueous environment.","authors":"Katarzyna Krzeminska, Malgorzata Sznitowska, Magdalena Wroblewska, Eliza Wolska, Katarzyna Winnicka","doi":"10.1080/10717544.2024.2372279","DOIUrl":"10.1080/10717544.2024.2372279","url":null,"abstract":"<p><p>The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2372279"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11249160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141589887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-11-08DOI: 10.1080/10717544.2024.2425156
Andong He, Yuye Huang, Chao Cao, Xuejin Li
{"title":"Advances in drug delivery systems utilizing blood cells and their membrane-derived microvesicles.","authors":"Andong He, Yuye Huang, Chao Cao, Xuejin Li","doi":"10.1080/10717544.2024.2425156","DOIUrl":"10.1080/10717544.2024.2425156","url":null,"abstract":"<p><p>The advancement of drug delivery systems (DDSs) in recent decades has demonstrated significant potential in enhancing the efficacy of pharmacological agents. Despite the approval of certain DDSs for clinical use, challenges such as rapid clearance from circulation, toxic accumulation in the body, and ineffective targeted delivery persist as obstacles to successful clinical application. Blood cell-based DDSs have emerged as a popular strategy for drug administration, offering enhanced biocompatibility, stability, and prolonged circulation. These DDSs are well-suited for systemic drug delivery and have played a crucial role in formulating optimal drug combinations for treating a variety of diseases in both preclinical studies and clinical trials. This review focuses on recent advancements and applications of DDSs utilizing blood cells and their membrane-derived microvesicles. It addresses the current therapeutic applications of blood cell-based DDSs at the organ and tissue levels, highlighting their successful deployment at the cellular level. Furthermore, it explores the mechanisms of cellular uptake of drug delivery vectors at the subcellular level. Additionally, the review discusses the opportunities and challenges associated with these DDSs.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2425156"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-01-05DOI: 10.1080/10717544.2023.2299594
Ellen K G Mhango, Benjamin R Sveinbjornsson, Bergthora S Snorradottir, Sveinbjorn Gizurarson
{"title":"Incompatibility of antimalarial drugs: challenges in formulating combination products for malaria.","authors":"Ellen K G Mhango, Benjamin R Sveinbjornsson, Bergthora S Snorradottir, Sveinbjorn Gizurarson","doi":"10.1080/10717544.2023.2299594","DOIUrl":"10.1080/10717544.2023.2299594","url":null,"abstract":"<p><p>Lipophilic drugs require more advance formulation, especially if the intention is to make solutions or semisolid formulations. This also accounts for most antimalarial drugs. Although some of these antimalarial drugs are soluble in lipid vehicles, few of them, such as lumefantrine (LF), are also poorly soluble in oily vehicles. Trying to dissolve and formulate LF as a liquid formulation together with other antimalarial drugs is, therefore, a major task. When mixed in solution together with artemether (AR), precipitation occurs, sometimes with LF precipitating out on its own, and sometimes with AR precipitating out alongside LF. In this study, it was hypothesized that the use of fatty acids could lead to enhanced solubility in lipid formulation. Addition of the fatty acid solved the dissolution challenges, making LF soluble for over a year at room temperature (21-23 °C); but further research is needed to test the mechanism of action of the fatty acid. In addition, design of experiments (MODDE<sup>®</sup> 13) revealed that the amount of fatty acid in the formulation was the only significant factor for LF precipitation.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2299594"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10773615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139097616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-08-05DOI: 10.1080/10717544.2024.2385376
Andrés Ramos-Valle, Henning Kirst, Mónica L Fanarraga
{"title":"Biodegradable silica nanoparticles for efficient linear DNA gene delivery.","authors":"Andrés Ramos-Valle, Henning Kirst, Mónica L Fanarraga","doi":"10.1080/10717544.2024.2385376","DOIUrl":"10.1080/10717544.2024.2385376","url":null,"abstract":"<p><p>Targeting, safety, scalability, and storage stability of vectors are still challenges in the field of nucleic acid delivery for gene therapy. Silica-based nanoparticles have been widely studied as gene carriers, exhibiting key features such as biocompatibility, simplistic synthesis, and enabling easy surface modifications for targeting. However, the ability of the formulation to incorporate DNA is limited, which restricts the number of DNA molecules that can be incorporated into the particle, thereby reducing gene expression. Here we use polymerase chain reaction (PCR)-generated linear DNA molecules to augment the coding sequences of gene-carrying nanoparticles, thereby maximizing nucleic acid loading and minimizing the size of these nanocarriers. This approach results in a remarkable 16-fold increase in protein expression six days post-transfection in cells transfected with particles carrying the linear DNA compared with particles bearing circular plasmid DNA. The study also showed that the use of linear DNA entrapped in DNA@SiO<sub>2</sub> resulted in a much more efficient level of gene expression compared to standard transfection reagents. The system developed in this study features simplicity, scalability, and increased transfection efficiency and gene expression over existing approaches, enabled by improved embedment capabilities for linear DNA, compared to conventional methods such as lipids or polymers, which generally show greater transfection efficiency with plasmid DNA. Therefore, this novel methodology can find applications not only in gene therapy but also in research settings for high-throughput gene expression screenings.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2385376"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11302475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-02-16DOI: 10.1080/10717544.2023.2300945
MeeiChyn Goh, Meng Du, Wang Rui Peng, Phei Er Saw, Zhiyi Chen
{"title":"Advancing burn wound treatment: exploring hydrogel as a transdermal drug delivery system.","authors":"MeeiChyn Goh, Meng Du, Wang Rui Peng, Phei Er Saw, Zhiyi Chen","doi":"10.1080/10717544.2023.2300945","DOIUrl":"10.1080/10717544.2023.2300945","url":null,"abstract":"<p><p>Burn injuries are prevalent and life-threatening forms that contribute significantly to mortality rates due to associated wound infections. The management of burn wounds presents substantial challenges. Hydrogel exhibits tremendous potential as an ideal alternative to traditional wound dressings such as gauze. This is primarily attributed to its three-dimensional (3D) crosslinked polymer network, which possesses a high water content, fostering a moist environment that supports effective burn wound healing. Additionally, hydrogel facilitates the penetration of loaded therapeutic agents throughout the wound surface, combating burn wound pathogens through the hydration effect and thereby enhancing the healing process. However, the presence of eschar formation on burn wounds obstructs the passive diffusion of therapeutics, impairing the efficacy of hydrogel as a wound dressing, particularly in cases of severe burns involving deeper tissue damage. This review focuses on exploring the potential of hydrogel as a carrier for transdermal drug delivery in burn wound treatment. Furthermore, strategies aimed at enhancing the transdermal delivery of therapeutic agents from hydrogel to optimize burn wound healing are also discussed.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2300945"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10878343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139746436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-08-21DOI: 10.1080/10717544.2024.2392755
Chunjiang Wei, Ziwen Gao, Martina Knabel, Martin Ulbricht, Stefan Senekowitsch, Peter Erfurt, Norman Maggi, Bastian Zwick, Thomas Eickner, Farnaz Matin-Mann, Anne Seidlitz, Thomas Lenarz, Verena Scheper
{"title":"Development of a drug delivering round window niche implant for cochlear pharmacotherapy.","authors":"Chunjiang Wei, Ziwen Gao, Martina Knabel, Martin Ulbricht, Stefan Senekowitsch, Peter Erfurt, Norman Maggi, Bastian Zwick, Thomas Eickner, Farnaz Matin-Mann, Anne Seidlitz, Thomas Lenarz, Verena Scheper","doi":"10.1080/10717544.2024.2392755","DOIUrl":"10.1080/10717544.2024.2392755","url":null,"abstract":"<p><strong>Background: </strong>There exists an unfulfilled requirement for effective cochlear pharmacotherapy. Controlled local drug delivery could lead to effective bioavailability. The round window niche (RWN), a cavity in the middle ear, is connected to the cochlea via a membrane through which drug can diffuse. We are developing individualized drug-eluting RWN implants (RNIs). To test their effectiveness in guinea pigs, a commonly used model in cochlear pharmacology studies, it is first necessary to develop guinea pig RNIs (GP-RNI).</p><p><strong>Methods: </strong>Since guinea pigs do not have a RWN such as it is present in humans and to reduce the variables in <i>in vivo</i> studies, a one-size-fits-all GP-RNI model was designed using 12 data sets of Dunkin-Hartley guinea pigs. The model was 3D-printed using silicone. The accuracy and precision of printing, distribution of the sample ingredient dexamethasone (DEX), biocompatibility, bio-efficacy, implantability and drug release were tested <i>in vitro</i>. The GP-RNI efficacy was validated in cochlear implant-traumatized guinea pigs <i>in vivo</i>.</p><p><strong>Results: </strong>The 3D-printed GP-RNI was precise, accurate and fitted in all tested guinea pig RWNs. DEX was homogeneously included in the silicone. The GP-RNI containing 1% DEX was biocompatible, bio-effective and showed a two-phase and sustained DEX release <i>in vitro</i>, while it reduced fibrous tissue growth around the cochlear implant <i>in vivo</i>.</p><p><strong>Conclusions: </strong>We developed a GP-RNI that can be used for precise inner ear drug delivery in guinea pigs, providing a reliable platform for testing the RNI's safety and efficacy, with potential implications for future clinical translation.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2392755"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142008520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-10-25DOI: 10.1080/10717544.2024.2417986
Haichang Li, Zhenghong Liu, Pu Zhang, Dahong Zhang
{"title":"The recent research progress in the application of the nanozyme-hydrogel composite system for drug delivery.","authors":"Haichang Li, Zhenghong Liu, Pu Zhang, Dahong Zhang","doi":"10.1080/10717544.2024.2417986","DOIUrl":"10.1080/10717544.2024.2417986","url":null,"abstract":"<p><p>Hydrogels, comprising 3D hydrophilic polymer networks, have emerged as promising biomaterial candidates for emulating the structure of biological tissues and delivering drugs through topical administration with good biocompatibility. Nanozymes can catalyze endogenous biomolecules, thereby initiating or inhibiting <i>in vivo</i> biological processes. A nanozyme-hydrogel composite inherits the biological functions of hydrogels and nanozymes, where the nanozyme serves as the catalytic core and the hydrogel forms the structural scaffold. Moreover, the composite can concentrate nanozymes in targeted lesions and catalyze the binding of a specific group of substrates, resulting in pathological microenvironment remodeling and drug-penetrating barrier impairment. The composite also shields nanozymes to prevent burst release during catalytic production and reduce related toxicity. Currently, the application of these composites has been extended to antibacterial, anti-inflammatory, anticancer, and tissue repair applications. In this review, we elucidate the preparation methods for nanozyme-hydrogel composites, provide compelling evidence of their advantages in drug delivery and provide a comprehensive overview of their biological application.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2417986"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug DeliveryPub Date : 2024-12-01Epub Date: 2024-07-01DOI: 10.1080/10717544.2024.2372285
María de Las Nieves Siles-Sánchez, Irene Fernández-Jalao, Laura Jaime De Pablo, Susana Santoyo
{"title":"Design of chitosan colon delivery micro/nano particles for an <i>Achillea millefolium</i> extract with antiproliferative activity against colorectal cancer cells.","authors":"María de Las Nieves Siles-Sánchez, Irene Fernández-Jalao, Laura Jaime De Pablo, Susana Santoyo","doi":"10.1080/10717544.2024.2372285","DOIUrl":"10.1080/10717544.2024.2372285","url":null,"abstract":"<p><p>In this study, chitosan low molecular weight (LCH) and chitosan medium molecular weight (MCH) were employed to encapsulate a yarrow extract rich in chlorogenic acid and dicaffeoylquinic acids (DCQAs) that showed antiproliferative activity against colon adenocarcinoma cells. The design of CH micro/nanoparticles to increase the extract colon delivery was carried out by using two different techniques: ionic gelation and spray drying. Ionic gelation nanoparticles obtained were smaller and presented higher yields values than spray-drying microparticles, but spray-drying microparticles showed the best performance in terms of encapsulation efficiency (EE) (> 94%), also allowing the inclusion of a higher quantity of extract. Spray-drying microparticles designed using LCH with an LCH:extract ratio of 6:1 (1.25 mg/mL) showed a mean diameter of 1.31 ± 0.21 µm and EE values > 93%, for all phenolic compounds studied. The release profile of phenolic compounds included in this formulation, at gastrointestinal pHs (2 and 7.4), showed for most of them a small initial release, followed by an increase at 1 h, with a constant release up to 3 h. Chlorogenic acid presented the higher release values at 3 h (56.91% at pH 2; 44.45% at pH 7.4). DCQAs release at 3 h ranged between 9.01- 40.73%, being higher for 1,5- and 3,4-DCQAs. After gastrointestinal digestion, 67.65% of chlorogenic and most DCQAs remained encapsulated. Therefore, spray-drying microparticles can be proposed as a promising vehicle to increase the colon delivery of yarrow phenolics compounds (mainly chlorogenic acid and DCQAs) previously described as potential agents against colorectal cancer.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2372285"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11221479/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mannose/stearyl chloride doubly functionalized polyethylenimine as a nucleic acid vaccine carrier to promote macrophage uptake.","authors":"Lu Bai, Xiaoqi Chen, Chengyu Li, Haijun Zhou, Yantao Li, Jijun Xiao, Fen Zhang, Hua Cheng, Mengmeng Zhou","doi":"10.1080/10717544.2024.2427138","DOIUrl":"10.1080/10717544.2024.2427138","url":null,"abstract":"<p><p>Transmembrane transport remains a significant challenge for nucleic acid vaccine vectors. Promoting the ability of immune cells, such as macrophages, to capture foreign stimuli is also an effective approach to improving cross-presentation. In addition, polyethyleneimine (PEI) has gained attention in the field of nucleic acid vaccine carriers due to its excellent gene transfection efficiency and unique proton buffering effect. However, although high molecular weight PEI exhibits high efficiency, its high-density positive charges make it highly toxic, which limits its application. In this study, mannose/stearyl chloride functionalized polyethylenimine (SA-Man-PEI) was prepared by functionalizing PEI (molecular weight of 25 kDa) with mannose with immunomodulatory and phagocyte targeting effects, and an alkyl hydrophobic chain segment, which could easily promote cell uptake. Moreover, the functionalized-PEI retains a strong proton buffering effect, which helps the carrier escape from the lysosome. The particle sizes of the composite particles formed by SA-Man-PEI and ovalbumin (OVA) were below 200 nm, with good storage stability at both 4 °C and 37 °C. At a drug concentration of 2 μg/mL, the cell survival rate of functionalized-PEI was 19.2% higher than that of unfunctionalized PEI. In vitro macrophage endocytosis experiments showed that SA-Man-PEI could significantly enhance the macrophage uptake of composite particles, compared to unfunctionalized PEI or single-functionalized PEI. This study offers a new approach for developing PEI as a nucleic acid vaccine carrier, which could simultaneously enhance cell targeting and promote cell uptake.</p>","PeriodicalId":11679,"journal":{"name":"Drug Delivery","volume":"31 1","pages":"2427138"},"PeriodicalIF":6.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565675/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}