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Keywords = drug delivery systems (DDSs)

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22 pages, 2122 KiB  
Review
Micro and Nano Drug Delivery Systems for the Treatment of Oral Mucositis: A Review
by Luciana Ângela Soares Maia, Tâmara Thaiane Almeida Siqueira, Carlos Alberto Arcelly Santos Bezerra, Jéssica Horana Pereira de Farias and Elquio Eleamen Oliveira
Pharmaceutics 2025, 17(8), 1025; https://doi.org/10.3390/pharmaceutics17081025 - 7 Aug 2025
Abstract
Oral mucositis (OM) is a severe inflammatory condition of the oral mucosa that is commonly associated with cancer therapies. Traditional treatments typically have limited efficacy and significant side effects, necessitating alternative approaches. Nanobased drug delivery systems (DDSs) present promising solutions, enhancing therapeutic outcomes [...] Read more.
Oral mucositis (OM) is a severe inflammatory condition of the oral mucosa that is commonly associated with cancer therapies. Traditional treatments typically have limited efficacy and significant side effects, necessitating alternative approaches. Nanobased drug delivery systems (DDSs) present promising solutions, enhancing therapeutic outcomes while minimizing side effects. This review aims to evaluate the use of nanobased DDSs to treat OM. To reach these aims, an extensive literature review was conducted using the following databases: BVS, PubMed, Scopus, and Web of Science. The search strategy included the keywords “microparticles,” “nanoparticles,” “drug delivery system,” “oral mucositis,” “therapy,” and “treatment,” combined with the Boolean operators “AND” and “OR.” After applying filters for language, relevance, full-text availability, exclusion of review articles, and removal of duplicates, a total of 32 articles were selected for analysis. Of the 32 studies included in this review, 25 employed polymeric micro- or nanosystems for the treatment of OM. Regarding the stage of investigation, 10 studies were conducted in vitro, 16 were conducted in vivo, and 6 corresponded to clinical trials. Compared with conventional drug delivery approaches, most of these studies reported improved therapeutic outcomes. These findings highlight the potential of nanosystems as innovative strategies for enhancing OM treatment. Nonetheless, challenges in large-scale manufacturing, including reproducibility and safety, and the limited number of clinical trials warrant careful consideration. Future research with larger clinical trials is essential to validate these findings and effectively guide clinical practice. Full article
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33 pages, 1598 KiB  
Review
Research Strategies and Methods of Hydrogels for Antitumor Drug Delivery
by Tianjiao Zeng, Lusi Chen, Toru Yoshitomi, Naoki Kawazoe, Yingnan Yang and Guoping Chen
Biomedicines 2025, 13(8), 1899; https://doi.org/10.3390/biomedicines13081899 - 4 Aug 2025
Viewed by 257
Abstract
Tumor treatments have substantially advanced through various approaches, including chemotherapy, radiotherapy, immunotherapy, and gene therapy. However, efficient treatment necessitates overcoming physiological barriers that impede the delivery of therapeutic agents to target sites. Drug delivery systems (DDSs) are a prominent research area, particularly in [...] Read more.
Tumor treatments have substantially advanced through various approaches, including chemotherapy, radiotherapy, immunotherapy, and gene therapy. However, efficient treatment necessitates overcoming physiological barriers that impede the delivery of therapeutic agents to target sites. Drug delivery systems (DDSs) are a prominent research area, particularly in tumor therapy. This review provides a comprehensive overview of hydrogel-based DDSs for tumor treatment, focusing on the strategies and designs of DDSs based on the unique pathophysiological characteristics of tumors. The design and preparation of hydrogel systems for DDSs are summarized and highlighted. The challenges and opportunities for translating hydrogel-based DDSs into clinical applications are discussed. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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26 pages, 4405 KiB  
Review
Nanocarriers for Combination Therapy in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review
by Iris Pontón and David Sánchez-García
Nanomaterials 2025, 15(15), 1139; https://doi.org/10.3390/nano15151139 - 22 Jul 2025
Viewed by 483
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers worldwide, characterized by late diagnosis, aggressive progression, and poor response to conventional monotherapies. Combination therapies have emerged as a promising approach to overcome multidrug resistance (MDR), enhance efficacy, and target the complex tumor [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers worldwide, characterized by late diagnosis, aggressive progression, and poor response to conventional monotherapies. Combination therapies have emerged as a promising approach to overcome multidrug resistance (MDR), enhance efficacy, and target the complex tumor microenvironment (TME). Nanoparticle-based drug delivery systems (DDSs) have gained significant attention for their ability to co-deliver multiple agents with controlled release profiles. This review comprehensively examines nanoparticle-based platforms developed for PDAC combination therapies, focusing on small-molecule drugs. The systems discussed are drawn from studies published between 2005 and 2025. Full article
(This article belongs to the Special Issue Nanoparticles for Multiple Drug Release)
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24 pages, 2632 KiB  
Article
Therapeutic Potential of Glucose Oxidase-Loaded Biogenic Mesoporous Silica Nanoparticles in Ovarian Cancer
by Andrea G. Uriostegui-Pena, Padmavati Sahare, Gabriel Luna-Bárcenas and Sujay Paul
Pharmaceuticals 2025, 18(7), 1060; https://doi.org/10.3390/ph18071060 - 18 Jul 2025
Viewed by 430
Abstract
Background/Objectives: Ovarian cancer (OC) remains one of the most lethal malignancies of the female reproductive system. Glucose oxidase (GOx) has emerged as a potential therapeutic agent in cancer treatment by inducing tumor starvation through glucose depletion. Nonetheless, its clinical application is constrained due [...] Read more.
Background/Objectives: Ovarian cancer (OC) remains one of the most lethal malignancies of the female reproductive system. Glucose oxidase (GOx) has emerged as a potential therapeutic agent in cancer treatment by inducing tumor starvation through glucose depletion. Nonetheless, its clinical application is constrained due to its systemic toxicity, immunogenicity, poor in vivo stability, and short half-life. These challenges can be addressed through nanotechnology; in particular, biogenic mesoporous silica nanoparticles (MSNs) offer promise as drug delivery systems (DDSs) that enhance therapeutic efficacy while minimizing side effects. Methods: Biogenic MSNs were extracted from the Equisetum myriochaetum plant via acid digestion, functionalized with 3-aminopropiltrietoxysilane (APTES) and glutaraldehyde (GTA), and loaded with GOx. The free and immobilized MSNs were characterized using FTIR, DLS, XRD, SEM/EDX, and BET techniques. A colorimetric approach was employed to quantify the enzymatic activity of both the free and immobilized GOx. The MTT assay was employed to assess the viability of SKOV3 cells. The obtained IC50 concentration of the nanoformulation was administered to SKOV3 cells to analyze the expression of cancer-related genes using RT-qPCR. Results: IC50 values of 60.77 ng/mL and 111.6 µg/mL were ascertained for the free and immobilized GOx, respectively. Moreover, a significant downregulation of the oncogene β-catenin (CTNNB1) was detected after 24 h with the nanoformulation. Conclusions: Our findings indicate that GOx-loaded biogenic MSNs may serve as a potential therapeutic agent for ovarian cancer. This is, to the best of our knowledge, the first report exploring the effect of GOx-loaded biogenic MSNs on SKOV3 cells. Full article
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30 pages, 3084 KiB  
Review
Antioxidants Acteoside and Orientin as Emerging Agents in Synergistic Cancer Therapy: A Focus on Innovative Applications
by Jagoda Szkudlarek, Ludwika Piwowarczyk and Anna Jelińska
Antioxidants 2025, 14(7), 855; https://doi.org/10.3390/antiox14070855 - 12 Jul 2025
Viewed by 419
Abstract
Cancers, particularly those resistant to treatment, stand as one of the most significant challenges in medicine. Frequently, available therapies need to be improved, underscoring the necessity for innovative treatment modalities. Over the years, there has been a resurgence of interest in natural plant [...] Read more.
Cancers, particularly those resistant to treatment, stand as one of the most significant challenges in medicine. Frequently, available therapies need to be improved, underscoring the necessity for innovative treatment modalities. Over the years, there has been a resurgence of interest in natural plant substances, which have been traditionally overlooked as anticancer agents. A prime example of this is natural antioxidants, such as acteoside (ACT) and orientin (ORI), which offer novel approaches to cancer treatment, emphasizing liver cancer compared to other cancer types. They reduce oxidative stress by activating the Nrf2/ARE pathway and exhibit anticancer activity, e.g., decreasing Bcl-2 and Bcl-XL expression and increasing Bax levels. This review explores the individual effects of ACT and ORI and their synergistic interactions with sorafenib, temozolomide, 5-fluorouracil (for ACT), celecoxib, and curcumin (for ORI), highlighting their enhanced anticancer efficacy. In addition, ACT and ORI successfully integrate into various drug delivery systems (DDSs), including metal-containing carriers such as nanoparticles (NPs), nanoshells (NSs), quantum dots (QDs), and liposomes as representative examples of lipid-based drug delivery systems (LBDDSs). Advanced methods, including nanotechnology, offer potential solutions to low bioavailability, paving the way for the use of these substances in anticancer therapy. Full article
(This article belongs to the Special Issue Oxidative Stress in Hepatic Diseases)
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16 pages, 2915 KiB  
Article
Extrusion-Based 3D Printing of Rutin Using Aqueous Polyethylene Oxide Gel Inks
by Oleh Koshovyi, Jyrki Heinämäki, Alina Shpychak, Andres Meos, Niklas Sandler Topelius and Ain Raal
Pharmaceutics 2025, 17(7), 878; https://doi.org/10.3390/pharmaceutics17070878 - 3 Jul 2025
Viewed by 422
Abstract
Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, with many of them being used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one-size-fits-all” dosage forms, such as conventional tablets or hard [...] Read more.
Background/Objectives. Flavonoids are a vast class of phenolic substances. To date, approximately 6000 plant-origin flavonoids have been discovered, with many of them being used in drug therapy. Therapeutic flavonoids are commonly formulated to conventional “one-size-fits-all” dosage forms, such as conventional tablets or hard capsules. However, the current trends in pharmacy and medicine are centred on personalised drug therapy and drug delivery systems (DDSs). Therefore, 3D printing is an interesting technique for designing and preparing novel personalised pharmaceuticals for flavonoids. The aim of the present study was to develop aqueous polyethylene oxide (PEO) gel inks loaded with rutin for semisolid extrusion (SSE) 3D printing. Methods. Rutin (a model substance for therapeutic flavonoids), Tween 80, PEO (MW approx. 900,000), ethanol, and purified water were used in PEO gels at different proportions. The viscosity and homogeneity of the gels were determined. The rutin–PEO gels were printed with a bench-top Hyrel 3D printer into lattices and discs, and their weight and effective surface area were investigated. Results. The key SSE 3D-printing process parameters were established and verified. The results showed the compatibility of rutin as a model flavonoid and PEO as a carrier polymer. The rutin content (%) and content uniformity of the 3D-printed preparations were assayed by UV spectrophotometry and high-performance liquid chromatography (HPLC). Conclusions. The most feasible aqueous PEO gel ink formulation for SSE 3D printing contained rutin 100 mg/mL and Tween 80 50 mg/mL in a 12% aqueous PEO gel. The 3D-printed dosage forms are intended for the oral administration of flavonoids. Full article
(This article belongs to the Special Issue 3D Printing of Drug Delivery Systems)
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21 pages, 842 KiB  
Review
Advances in Local Drug Delivery for Periodontal Treatment: Present Strategies and Future Directions
by Mayuka Nakajima, Mayuko Yanagawa, Honoka Takikawa, Truong Tran Thien, Lorena Zegarra-Caceres, Chunyang Yan and Koichi Tabeta
Biomolecules 2025, 15(6), 903; https://doi.org/10.3390/biom15060903 - 19 Jun 2025
Viewed by 967
Abstract
Periodontitis is a highly prevalent, irreversible inflammatory disease characterized by the destruction of tooth-supporting tissues, eventually leading to tooth loss. Conventional treatment involves the mechanical removal of the subgingival biofilm, which is a major cause of gingival inflammation. However, the inaccessibility of deep-seated [...] Read more.
Periodontitis is a highly prevalent, irreversible inflammatory disease characterized by the destruction of tooth-supporting tissues, eventually leading to tooth loss. Conventional treatment involves the mechanical removal of the subgingival biofilm, which is a major cause of gingival inflammation. However, the inaccessibility of deep-seated polymicrobial biofilms limits its effectiveness. Despite the adjunct use of systemic antimicrobials, their low site-specific bioavailability and systemic side effects remain concerns. Local drug administration offers a targeted alternative. However, the dynamic oral environment, which is characterized by continuous salivary and gingival crevicular fluid flow, poses challenges in maintaining therapeutic drug levels. Drug delivery systems (DDSs) provide technical solutions to overcome these limitations. With advancements in materials science and nanotechnology, diverse local DDS (LDDS) formulations tailored for periodontal applications have been developed. While traditionally focused on infection control, the application of LDDSs has expanded beyond antimicrobial therapy. Increasing attention has been paid to LDDS-based regenerative strategies, which aim to overcome the limitations of conventional regenerative therapies. This review aims to provide a comprehensive overview of the current and emerging DDS strategies in periodontal therapy, focusing on their applications in infection management and bone regeneration and discussing their limitations and prospects for clinical translation. Full article
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25 pages, 2139 KiB  
Review
Next-Generation Drug Delivery for Neurotherapeutics: The Promise of Stimuli-Triggered Nanocarriers
by Radka Boyuklieva, Nikolay Zahariev, Plamen Simeonov, Dimitar Penkov and Plamen Katsarov
Biomedicines 2025, 13(6), 1464; https://doi.org/10.3390/biomedicines13061464 - 13 Jun 2025
Viewed by 656
Abstract
Nanotherapeutics have emerged as novel unparalleled drug delivery systems (DDSs) for the treatment of neurodegenerative disorders. By applying different technological approaches, nanoparticles can be engineered to possess different functionalities. In recent years, the developed, stimuli-responsive nanocarriers stand out as novel complex DDSs ensuring [...] Read more.
Nanotherapeutics have emerged as novel unparalleled drug delivery systems (DDSs) for the treatment of neurodegenerative disorders. By applying different technological approaches, nanoparticles can be engineered to possess different functionalities. In recent years, the developed, stimuli-responsive nanocarriers stand out as novel complex DDSs ensuring selective and specific drug delivery in response to different endogenous and exogenous stimuli. Due to the multifaceted pathophysiology of the nervous system, a major challenge in modern neuropharmacology is the development of effective therapies ensuring high efficacy and low toxicity. Functionalization of the nanocarriers to react to specific microenvironmental changes in the nervous system tissues or external stimulations significantly enhances the efficacy of drug delivery. This review discusses the microenvironmental characteristics of some common neurological diseases in-depth and provides a comprehensive overview on the progress of the development of exogenous and endogenous stimuli-sensitive nanocarriers for the treatment of Alzheimer’s and Parkinson’s disease. Full article
(This article belongs to the Special Issue Advanced Research in Neuroprotection)
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57 pages, 5820 KiB  
Review
Surfactant-Enabled Nanocarriers in Breast Cancer Therapy: Targeted Delivery and Multidrug Resistance Reversal
by Ashirwad Jadhav and Karuppiah Nagaraj
Pharmaceutics 2025, 17(6), 779; https://doi.org/10.3390/pharmaceutics17060779 - 13 Jun 2025
Cited by 1 | Viewed by 772
Abstract
Breast cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Its treatment is complicated by molecular heterogeneity and the frequent development of multidrug resistance (MDR). Conventional drug delivery approaches are often limited by poor aqueous solubility, rapid systemic clearance, [...] Read more.
Breast cancer remains a leading cause of cancer-related morbidity and mortality among women worldwide. Its treatment is complicated by molecular heterogeneity and the frequent development of multidrug resistance (MDR). Conventional drug delivery approaches are often limited by poor aqueous solubility, rapid systemic clearance, non-specific biodistribution, and off-target toxicity. This review will critically explore the possibility of surfactant-based drug delivery systems (DDSs) in addressing the constraints of standard breast cancer treatments. It focuses on the mechanisms by which surfactants promote solubility, facilitate cellular uptake, and overcome drug resistance, while also analyzing current therapeutic success and future directions. A thorough review of preclinical and clinical investigations was undertaken, focusing on important surfactant-based DDSs such as polymeric micelles, nanoemulsions, liposomes, and self-emulsifying systems (SEDDSs). Mechanistic insights into surfactant functions, such as membrane permeabilization and efflux pump inhibition, were studied alongside delivery systems incorporating ligands and co-loaded medicines. Pluronic® micelles, TPGS-based systems, biosurfactant-stabilized nanoparticles, and lipid-based carrier surfactant platforms improve medication solubility, stability, and delivery. Genexol® are examples of formulations demonstrating effective use and FDA translational potential. These systems now incorporate stimuli-responsive release mechanisms—such as pH, temperature, redox, immuno- and photodynamic treatment—artificial intelligence treatment design, and tailored treatment advancement, and responsive tailoring. Surfactant-enabled DDSs can improve breast cancer care. Innovative approaches for personalized oncology treatment are countered by the enduring challenges of toxicity, regulatory hurdles, and diminished scalability. Full article
(This article belongs to the Special Issue Natural Nanoparticle for Cancer Diagnosis and Treatment, 2nd Edition)
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34 pages, 2275 KiB  
Review
A State-of-the-Art Review on Recent Biomedical Application of Polysaccharide-Based Niosomes as Drug Delivery Systems
by Andreea-Teodora Iacob, Andra Ababei-Bobu, Oana-Maria Chirliu, Florentina Geanina Lupascu, Ioana-Mirela Vasincu, Maria Apotrosoaei, Bianca-Stefania Profire, Georgiana-Roxana Tauser, Dan Lupascu and Lenuta Profire
Polymers 2025, 17(11), 1566; https://doi.org/10.3390/polym17111566 - 4 Jun 2025
Viewed by 864
Abstract
The development of nanocarriers for drug delivery has drawn a lot of attention due to the possibility for tailored delivery to the ill region while preserving the neighboring healthy tissue. In medicine, delivering drugs safely and effectively has never been easy; therefore, the [...] Read more.
The development of nanocarriers for drug delivery has drawn a lot of attention due to the possibility for tailored delivery to the ill region while preserving the neighboring healthy tissue. In medicine, delivering drugs safely and effectively has never been easy; therefore, the creation of surfactant-based vesicles (niosomes) to enhance medication delivery has gained attention in the past years. Niosomes (NIOs) are versatile drug delivery systems that facilitate applications varying from transdermal transport to targeted brain delivery. These self-assembling vesicular nano-carriers are formed by hydrating cholesterol, non-ionic surfactants, and other amphiphilic substances. The focus of the review is to report on the latest NIO-type formulations which also include biopolymers from the polysaccharide class, highlighting their role in the development of these drug delivery systems (DDSs). The NIO and polysaccharide types, together with the recent pharmaceutical applications such as ocular, oral, nose-to brain, pulmonary, cardiac, and transdermal drug delivery, are all thoroughly summarized in this review, which offers a comprehensive compendium of polysaccharide-based niosomal research to date. Lastly, this delivery system’s limits and prospects are also examined. Full article
(This article belongs to the Special Issue Biomedical Applications of Polymeric Materials, 3rd Edition)
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15 pages, 2460 KiB  
Article
Exploration of a Novel Catalytic Approach for Synthesizing Glycolide and ε-Caprolactone Copolymers and Their Application as Carriers for Paclitaxel
by Rafał Wyrębiak, Ramona Figat, Ewa Oledzka, Adam Kasiński, Karolina Kędra, Anna Laskowska and Marcin Sobczak
Molecules 2025, 30(11), 2318; https://doi.org/10.3390/molecules30112318 - 25 May 2025
Viewed by 638
Abstract
Biodegradable polyesters serve as matrices in pharmaceutical applications for the controlled release of therapeutic agents. These polymers are essential in the advancement of drug delivery systems (DDSs) that facilitate the gradual drug release over a predetermined duration. Therefore, this study introduces the novel [...] Read more.
Biodegradable polyesters serve as matrices in pharmaceutical applications for the controlled release of therapeutic agents. These polymers are essential in the advancement of drug delivery systems (DDSs) that facilitate the gradual drug release over a predetermined duration. Therefore, this study introduces the novel use of a diethyl zinc/propyl gallate catalytic system to synthesize glycolide/ε-caprolactone copolymers (PGCL) for subsequent biomedical applications. A total of twenty-four biodegradable copolymeric matrices, characterized by a highly random microstructure and an average molecular weight (Mn) ranging from approximately 27 to 62 kDa, were synthesized and analyzed. The resulting copolymer samples underwent Neutral Red Uptake (NRU) and Umu tests, revealing no signs of cyto- or genotoxicity. Furthermore, a hemolysis assay was conducted on selected samples, indicating their suitability for intravenous administration. Finally, a release study of paclitaxel (PACL) from one of the synthesized matrices demonstrated a sustained and highly controlled drug release profile, following first-order kinetics and the Fickian diffusion mechanism. Full article
(This article belongs to the Special Issue Exclusive Feature Papers in Macromolecular Chemistry)
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20 pages, 10181 KiB  
Article
Encapsulation of Transforming Growth Factor-β3 in Poly(hydroxybutyrate-co-hydroxyvalerate) Nanoparticles for Enhanced Cartilage Tissue Engineering
by Ana Isabel Rodríguez-Cendal, José Señarís-Rodríguez, María Piñeiro-Ramil, Loreto Cabarcos-Mouzo, María del Carmen Veiga-Barbazán, Rosa María Mejide-Faílde, Francisco Javier de Toro-Santos, Isaac Manuel Fuentes-Boquete and Silvia María Díaz-Prado
Int. J. Mol. Sci. 2025, 26(11), 4997; https://doi.org/10.3390/ijms26114997 - 22 May 2025
Viewed by 532
Abstract
Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) is a naturally occurring biopolymer belonging to the polyhydroxyalkanoate (PHA) family. Due to its excellent properties (biocompatible, biodegradable, and non-toxic), this biopolymer is presented as a very suitable option for use in regenerative therapy as a drug delivery system (DDS). The [...] Read more.
Poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) is a naturally occurring biopolymer belonging to the polyhydroxyalkanoate (PHA) family. Due to its excellent properties (biocompatible, biodegradable, and non-toxic), this biopolymer is presented as a very suitable option for use in regenerative therapy as a drug delivery system (DDS). The protein encapsulated in this study is transforming growth factor β3 (TGF-β3), which plays a key role in the chondrogenic differentiation of mesenchymal stem cells (MSCs). The main objective of this work is to evaluate the efficacy of PHBV nanoparticles (NPs) produced from a dairy by-product (whey) as a DDS of TGF-β3 for cartilage regeneration and extracellular matrix (ECM) synthesis and to reduce the complications associated with multiple high doses of TGF-β3 in its free form. For this purpose, biopolymer cytotoxicity, factor release, cell viability, cell proliferation, and differentiation were analyzed. The results showed that the biomaterial purified with chloroform and ethanol, either by single or double precipitation, was not toxic to cells. A sustained release profile was observed, reaching its maximum around day 4. The TGF-β3 NPs promoted the differentiation of MSCs into chondrocytes and the formation of ECM. In conclusion, PHBV demonstrated its potential as an optimal material for DDSs in cartilage regenerative therapy, effectively addressing the key challenge of the need for a single delivery method to reduce complications associated with multiple high doses of TGF-β3. Full article
(This article belongs to the Special Issue Bone and Cartilage Injury and Repair: Molecular Aspects)
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15 pages, 2411 KiB  
Article
Versatile Polycaprolactone-Based Drug Delivery System with Enhanced Cytocompatibility and Antibacterial Activity
by Celine Guder, Anja Hofmann, Therese Schüler, Torsten Sterzenbach, Hans-Peter Wiesmann, Katrin Lorenz, Christian Hannig, Christian Reeps and Benjamin Kruppke
J. Funct. Biomater. 2025, 16(5), 182; https://doi.org/10.3390/jfb16050182 - 15 May 2025
Viewed by 1029
Abstract
Common antibiotic therapies to treat bacterial infections are associated with systemic side effects and the development of resistance, directly connected to duration and dosage. Local drug delivery systems (DDSs) offer an alternative by localising antibiotics and thereby limiting their side effects while reducing [...] Read more.
Common antibiotic therapies to treat bacterial infections are associated with systemic side effects and the development of resistance, directly connected to duration and dosage. Local drug delivery systems (DDSs) offer an alternative by localising antibiotics and thereby limiting their side effects while reducing the dosage necessary. A biodegradable polyester polycaprolactone (PCL)-based DDS was thus produced, containing various clinically relevant drugs. It was shown that the incorporation of four distinct antibiotic classes (amoxicillin, doxycycline, metronidazole and rifampicin), with very high mass fractions ranging up to 20 wt%, was feasible within the PCL matrix. This DDS showed the capacity for effective and sustained release. The release kinetics over 14 days were proven, showing a significant decrease in cytotoxicity with smooth muscle cells as well as an antibacterial effect on (1) aerobic, (2) anaerobic, (3) Gram-positive and (4) Gram-negative pathogens in vitro. The DDS demonstrated a markedly diminished cytotoxic impact owing to sustained release in comparison to pure antibiotics, while simultaneously maintaining their antibacterial efficacy. In conclusion, DDSs are a more tolerable form of antibiotics administration due to the hydrophobic PCL matrix causing a slower diffusion-controlled release, proven as a release mechanism via the Peppa–Sahlin model. Full article
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32 pages, 5142 KiB  
Review
The Art of PEGylation: From Simple Polymer to Sophisticated Drug Delivery System
by Davit Makharadze, Luis J. del Valle, Ramaz Katsarava and Jordi Puiggalí
Int. J. Mol. Sci. 2025, 26(7), 3102; https://doi.org/10.3390/ijms26073102 - 27 Mar 2025
Cited by 3 | Viewed by 4677
Abstract
The development of effective drug delivery systems (DDSs) is important for cancer and infectious disease treatment to overcome low bioavailability, rapid clearance and the toxicity of the therapeutic towards non-targeted healthy tissues. This review discusses how PEGylation, the attachment of poly(ethylene glycol) (PEG) [...] Read more.
The development of effective drug delivery systems (DDSs) is important for cancer and infectious disease treatment to overcome low bioavailability, rapid clearance and the toxicity of the therapeutic towards non-targeted healthy tissues. This review discusses how PEGylation, the attachment of poly(ethylene glycol) (PEG) molecules to nanoparticles (NPs), enhances drug pharmacokinetics by creating a “stealth effect”. We provide the synthesis methods for several PEG derivatives, their conjugation with NPs, proteins and characterization using modern analytical tools. This paper focuses particularly on covalent conjugation and self-assembly strategies for successful PEGylation and discusses the influence of PEG chain length, density and conformation on drug delivery efficiency. Despite the PEGylation benefits, there are several challenges associated with it, including immunogenicity and reduced therapeutic efficacy due to accelerated blood clearance. Therefore, the balance between PEGylation benefits and its immunogenic risks remains a critical area of investigation. Full article
(This article belongs to the Special Issue Nanotechnology in Targeted Drug Delivery 2.0)
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20 pages, 1459 KiB  
Review
The Co-Delivery of Natural Products and Small RNAs for Cancer Therapy: A Review
by Xuyi Wang, Shuang Li, Zelong Wang, Baorong Kang and Hong Yan
Molecules 2025, 30(7), 1495; https://doi.org/10.3390/molecules30071495 - 27 Mar 2025
Viewed by 781
Abstract
This review summarizes the research progress in the co-delivery of natural products (NPs) and small RNAs in cancer therapy. NPs such as paclitaxel, camptothecin, and curcumin possess multi-target antitumor effects, but their applications are limited by drug resistance and non-specific distribution. Small RNAs [...] Read more.
This review summarizes the research progress in the co-delivery of natural products (NPs) and small RNAs in cancer therapy. NPs such as paclitaxel, camptothecin, and curcumin possess multi-target antitumor effects, but their applications are limited by drug resistance and non-specific distribution. Small RNAs can achieve precise antitumor effects through gene regulation, yet their delivery efficiency is low, and they are prone to degradation by nucleases. Nanomaterial-based drug delivery systems (nano-DDSs) provide an efficient platform for the co-delivery of both, which can enhance the targeting of their delivery and improve the synergistic antitumor effects simultaneously. The mechanisms of the antitumor action of natural compounds and small RNAs, the design and application of nanocarriers, and the latest research progress in co-delivery systems are introduced in detail in this paper. The application prospects of the co-delivery of natural compounds and small RNAs in cancer therapy are also discussed. Full article
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