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Search Results (1,098)

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Keywords = alternative drug delivery

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51 pages, 2489 KiB  
Review
Immunomodulatory Effects of Gold Nanoparticles: Impacts on Immune Cells and Mechanisms of Action
by Khadijeh Koushki, Prapannajeet Biswal, Geraldine Vidhya Vijay, Mahvash Sadeghi, Sajad Dehnavi, Ngoc Tuyet Tra, Sai Kumar Samala, Mahdieh Yousefi Taba, Arjun Balaji Vasan, Emily Han, Yuri Mackeyev and Sunil Krishnan
Nanomaterials 2025, 15(15), 1201; https://doi.org/10.3390/nano15151201 - 6 Aug 2025
Abstract
Traditional anti-inflammatory medications—such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs—are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect [...] Read more.
Traditional anti-inflammatory medications—such as corticosteroids, biological agents, and non-steroidal anti-inflammatory drugs—are commonly employed to mitigate inflammation, despite their potential for debilitating side effects. There is a growing need for alternative next-generation therapies for symptomatic, unchecked, and/or detrimental inflammation with more favorable adverse effect profiles. The long history of use of gold salts as anti-inflammatory agents and the more recent exploration of gold nanoparticle (AuNP) formulations for clinical indications suggest that the targeted delivery of nanoparticles to inflammatory sites may be a promising approach worth investigating. Coupled with peptides that specifically target immune cells, AuNPs could potently counteract inflammation. Here, we provide an overview of the selective infiltration of AuNPs into immune cells and summarize their interactions with and impact on these cells. Additionally, we provide a comprehensive mechanistic summary of how AuNPs exert their anti-inflammatory effects. Full article
(This article belongs to the Special Issue Roadmaps for Nanomaterials in Radiation Therapy)
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14 pages, 5990 KiB  
Article
Distinctive Features of the Buffer Capacity of Polyelectrolyte Microcapsules Formed on MnCO3 Core
by Aleksandr L. Kim, Alexey V. Dubrovskii and Sergey A. Tikhonenko
Polymers 2025, 17(15), 2149; https://doi.org/10.3390/polym17152149 - 6 Aug 2025
Abstract
The development of layer-by-layer polyelectrolyte microcapsules (PMCs) with defined buffer capacity (BC) is a key task for creating stable systems in biomedicine and materials science. Manganese carbonate (MnCO3), which shares properties with CaCO3 and the ability to form hollow structures, [...] Read more.
The development of layer-by-layer polyelectrolyte microcapsules (PMCs) with defined buffer capacity (BC) is a key task for creating stable systems in biomedicine and materials science. Manganese carbonate (MnCO3), which shares properties with CaCO3 and the ability to form hollow structures, represents a promising alternative. However, its interaction with polyelectrolytes and its influence on BC remain insufficiently studied. This research focuses on determining the BC of PMCs templated on MnCO3 cores under varying ionic strength (0.22–3 M NaCl) and temperature (60–90 °C), as well as comparing the results with PMCs templated on CaCO3 and PS cores. It was found that MnCO3-based PMCs (PMCMn) exhibit hybrid behavior between CaCO3- and PS-based PMCs: the BC dynamics of PMCMn and CaCO3-based PMCs (PMCCa) in water are identical. At different ionic strength at pH < 5, the BC of PMCMn and PS-based PMCs (PMCPS) remains unchanged, while at pH > 8.5, the BC of PMCMn increases only at 3 M NaCl. The BC of PMCMn remains stable under heating, whereas the BC of PMCCa and PMCPS decreases. These results confirm that the choice of core material dictates PMC functionality, paving the way for adaptive systems in biosensing and controlled drug delivery. Full article
(This article belongs to the Special Issue Stimuli-Responsive Polymers: Advances and Prospects)
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33 pages, 4132 KiB  
Review
Mechanical Properties of Biodegradable Fibers and Fibrous Mats: A Comprehensive Review
by Ehsan Niknejad, Reza Jafari and Naser Valipour Motlagh
Molecules 2025, 30(15), 3276; https://doi.org/10.3390/molecules30153276 - 5 Aug 2025
Abstract
The growing demand for sustainable materials has led to increased interest in biodegradable polymer fibers and nonwoven mats due to their eco-friendly characteristics and potential to reduce plastic pollution. This review highlights how mechanical properties influence the performance and suitability of biodegradable polymer [...] Read more.
The growing demand for sustainable materials has led to increased interest in biodegradable polymer fibers and nonwoven mats due to their eco-friendly characteristics and potential to reduce plastic pollution. This review highlights how mechanical properties influence the performance and suitability of biodegradable polymer fibers across diverse applications. This covers synthetic polymers such as polylactic acid (PLA), polyhydroxyalkanoates (PHAs), polycaprolactone (PCL), polyglycolic acid (PGA), and polyvinyl alcohol (PVA), as well as natural polymers including chitosan, collagen, cellulose, alginate, silk fibroin, and starch-based polymers. A range of fiber production methods is discussed, including electrospinning, centrifugal spinning, spunbonding, melt blowing, melt spinning, and wet spinning, with attention to how each technique influences tensile strength, elongation, and modulus. The review also addresses advances in composite fibers, nanoparticle incorporation, crosslinking methods, and post-processing strategies that improve mechanical behavior. In addition, mechanical testing techniques such as tensile test machine, atomic force microscopy, and dynamic mechanical analysis are examined to show how fabrication parameters influence fiber performance. This review examines the mechanical performance of biodegradable polymer fibers and fibrous mats, emphasizing their potential as sustainable alternatives to conventional materials in applications such as tissue engineering, drug delivery, medical implants, wound dressings, packaging, and filtration. Full article
(This article belongs to the Section Materials Chemistry)
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20 pages, 1545 KiB  
Review
Nanomedicine as a Promising Treatment Approach for Obesity
by Abeer Alanazi, Alexander Craven, Spiridon V. Spirou, Maria Jose Santos-Martinez, Carlos Medina and Oliviero L. Gobbo
J. Nanotheranostics 2025, 6(3), 21; https://doi.org/10.3390/jnt6030021 - 5 Aug 2025
Abstract
Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by [...] Read more.
Obesity is a chronic disorder associated with serious comorbidities such as diabetes, cardiovascular disease, and cancer. Conventional pharmacological treatments often suffer from limited efficacy, poor selectivity, and undesirable side effects, highlighting the need for more effective alternatives. Nanomedicine offers a promising approach by overcoming these limitations through targeted drug delivery and enhanced therapeutic precision. This review examines key nanotechnological strategies in obesity management, including targeting white adipose tissue (WAT) and the vascular marker prohibitin, promoting WAT browning, and utilizing photothermal therapy and magnetic hyperthermia as nanotheranostic tools. We discuss major nanomedicine platforms—such as liposomes, nanoemulsions, and polymeric nanoparticles—alongside emerging applications in gene nanotherapy and herbal formulations. Potential toxicity concerns are also addressed. In summary, nanomedicine holds substantial potential to revolutionize obesity treatment through targeted, effective, and multifunctional therapeutic strategies. Full article
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10 pages, 223 KiB  
Case Report
Total Intravenous Anesthesia Using Target-Controlled Infusion with Propofol for Category 1 Emergency Cesarean Section in Patients with Preeclampsia with Severe Features
by Janos Szederjesi, Emoke Almasy, Oana Elena Branea and Matild Keresztes
Life 2025, 15(8), 1237; https://doi.org/10.3390/life15081237 - 4 Aug 2025
Abstract
Preeclampsia with severe features presents major anesthetic challenges, particularly in category 1 cesarean sections, in which rapid, safe, and hemodynamically stable induction is critical. Neuraxial techniques may be controversial due to neurological symptoms, making general anesthesia a viable option. However, traditional general anesthesia [...] Read more.
Preeclampsia with severe features presents major anesthetic challenges, particularly in category 1 cesarean sections, in which rapid, safe, and hemodynamically stable induction is critical. Neuraxial techniques may be controversial due to neurological symptoms, making general anesthesia a viable option. However, traditional general anesthesia may exacerbate hypertension and increase maternal and fetal risks. Two primigravida patients with elevated blood pressure and neurological symptoms underwent category 1 cesarean delivery under TIVA-TCI with propofol, using the Marsh model. Hemodynamic stability, drug dosing, and maternal–neonatal outcomes were monitored. Sufentanil was administered for analgesia; neuromuscular blockade was achieved with rocuronium and reversed with sugammadex. No BIS or TOF monitoring was available. Both patients maintained stable hemodynamics and oxygenation throughout surgery. Intubation was successfully performed at an effect-site concentration of 3.5 µg/mL. Neonatal Apgar scores were within acceptable limits. No major complications occurred intraoperatively or postoperatively. TCI allowed individualized dosing and smooth emergence. TIVA-TCI with propofol appears to be a viable alternative to volatile-based general anesthesia in category 1 emergencies for cesarean sections for patients with preeclampsia with severe features, especially when neuraxial anesthesia is controversial. It offers hemodynamic stability and controlled depth of anesthesia, though its use requires experience and may not be optimal in cases requiring ultra-rapid induction. Full article
(This article belongs to the Special Issue Prevention, Diagnosis, and Treatment of Gestational Diseases)
35 pages, 1395 KiB  
Review
Local Chemotherapy of Skin Pre-Neoplastic Lesions and Malignancies from the Perspective of Current Pharmaceutics
by Nadezhda Ivanova
Pharmaceutics 2025, 17(8), 1009; https://doi.org/10.3390/pharmaceutics17081009 - 1 Aug 2025
Viewed by 396
Abstract
In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while [...] Read more.
In the preceding and early stages of cancer progression, local drug delivery to pre-cancerous and cancerous skin lesions may be applied as an alternative or supplementary therapy. At present, 5-Fluorouracil, imiquimod, and tirbanibulin creams and ointments have established their place in practice, while several other active pharmaceutical ingredients (APIs) (e.g., calcipotriol, tretinoin, diclofenac) have been repurposed, used off-label, or are currently being investigated in mono- or combined chemotherapies of skin cancers. Apart from them, dozens to hundreds of therapeutics of natural and synthetic origin are proven to possess anti-tumor activity against melanoma, squamous cell carcinoma (SCC), and other skin cancer types in in vitro studies. Their clinical introduction is most often limited by low skin permeability, challenged targeted drug delivery, insufficient chemical stability, non-selective cytotoxicity, or insufficient safety data. A variety of prodrug and nanotechnological approaches, including vesicular systems, micro- and nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanoparticles, and others, offer versatile solutions for overcoming the biophysical barrier function of the skin and the undesirable physicochemical nature of some drug molecules. This review aims to present the most significant aspects and latest achievements on the subject. Full article
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19 pages, 1625 KiB  
Review
The Potential of Functional Hydrogels in Burns Treatment
by Nathalie S. Ringrose, Ricardo W. J. Balk, Susan Gibbs, Paul P. M. van Zuijlen and H. Ibrahim Korkmaz
Gels 2025, 11(8), 595; https://doi.org/10.3390/gels11080595 - 31 Jul 2025
Viewed by 136
Abstract
Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, [...] Read more.
Burn injuries are complex and require effective wound management strategies. Traditional treatments, such as dermal templates, are limited by simplified extracellular matrix (ECM) composition (e.g., collagen-elastin or collagen-glycosaminoglycan), sheet-based formats, and frequent use of animal-derived materials. These limitations can reduce wound conformity, biocompatibility, and integration with host tissue. Functional hydrogels are being explored as alternatives due to properties such as high water content, biodegradability, adhesiveness, antimicrobial activity, and support for angiogenesis. Unlike standard templates, hydrogels can adapt to irregular wound shapes as in burn wounds and reach deeper tissue layers, supporting moisture retention, cell migration, and controlled drug delivery. These features may improve the wound environment and support healing in burns of varying severity. This review outlines recent developments in functional hydrogel technologies and compares them to current clinical treatments for burn care. Emphasis is placed on the structural and biological features that influence performance, including material composition, bioactivity, and integration capacity. Through an exploration of key mechanisms of action and clinical applications, this review highlights the benefits and challenges associated with hydrogel technology, providing insights into its future role in burn care. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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26 pages, 1426 KiB  
Review
Mycobacteriophages in the Treatment of Mycobacterial Infections: From Compassionate Use to Targeted Therapy
by Magdalena Druszczynska, Beata Sadowska, Agnieszka Zablotni, Lesia Zhuravska, Jakub Kulesza and Marek Fol
Appl. Sci. 2025, 15(15), 8543; https://doi.org/10.3390/app15158543 (registering DOI) - 31 Jul 2025
Viewed by 316
Abstract
This review addresses the urgent need for alternative strategies to combat drug-resistant mycobacterial infections, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, as well as non-tuberculous mycobacterial (NTM) diseases. Traditional antibiotics are increasingly limited by resistance, toxicity, and poor efficacy, particularly in immunocompromised [...] Read more.
This review addresses the urgent need for alternative strategies to combat drug-resistant mycobacterial infections, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis, as well as non-tuberculous mycobacterial (NTM) diseases. Traditional antibiotics are increasingly limited by resistance, toxicity, and poor efficacy, particularly in immunocompromised patients. A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar, covering publications primarily from 2000 to 2025. Only articles published in English were included to ensure consistency in data interpretation. Search terms included “mycobacteriophages,” “phage therapy,” “drug-resistant mycobacteria, “diagnostic phages,” and “phage engineering.” The review examines the therapeutic and diagnostic potential of mycobacteriophages—viruses that specifically infect mycobacteria—focusing on their molecular biology, engineering advances, delivery systems, and clinical applications. Evidence suggests that mycobacteriophages offer high specificity, potent bactericidal activity, and adaptability, positioning them as promising candidates for targeted therapy. Although significant obstacles remain—including immune interactions, limited host range, and regulatory challenges—rapid progress in synthetic biology and delivery platforms continues to expand their clinical potential. As research advances and clinical frameworks evolve, mycobacteriophages are poised to become a valuable asset in the fight against drug-resistant mycobacterial diseases, offering new precision-based solutions where conventional therapies fail. Full article
(This article belongs to the Special Issue Tuberculosis—a Millennial Disease in the Age of New Technologies)
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15 pages, 1743 KiB  
Article
Development of Bioresponsive Poloxamer-Based Self-Nanoemulsifying System for Enhanced Febuxostat Bioavailability: Solidification Strategy Using I-Optimal Approach
by Abdelrahman Y. Sherif and Ehab M. Elzayat
Pharmaceutics 2025, 17(8), 975; https://doi.org/10.3390/pharmaceutics17080975 - 28 Jul 2025
Viewed by 245
Abstract
Background/Objectives: The major limitations of self-nanoemulsifying systems include complex processing and expensive instrumentation required for solidification approaches. In this study, smart poloxamer-based solidification strategies were used to develop and optimize febuxostat-loaded formulations. Methods: A self-nanoemulsifying drug delivery system (SNEDDS) component was selected based [...] Read more.
Background/Objectives: The major limitations of self-nanoemulsifying systems include complex processing and expensive instrumentation required for solidification approaches. In this study, smart poloxamer-based solidification strategies were used to develop and optimize febuxostat-loaded formulations. Methods: A self-nanoemulsifying drug delivery system (SNEDDS) component was selected based on solubility and emulsification tests. The influence of poloxamer molecular weight (low or high) and its concentration (2–10% w/w) on formulation performance was assessed through the design of experiments. Finally, in-vitro melting assessment and a comparative dissolution test were performed on the optimized SNEDDS formulation. Results: Imwitor 988 and Tween 20 were selected to prepare the formulations. Increasing the molecular weight and concentration of the poloxamer significantly increased the temperature and time required for the melting of the SNEDDS formulation. The optimized SNEDDS formulation comprised 3.98% w/w poloxamer 188, which melts at 36 °C within 111 s. In-vitro melting showed that the formulation completely converted to a liquid state upon exposure to body temperature. Finally, the optimized SNEDDS formulation exhibited superior dissolution efficiency (96.66 ± 0.28%) compared to raw febuxostat (72.09 ± 4.33%) and marketed tablets (82.23 ± 3.10%). Conclusions: The poloxamer-based approach successfully addressed the limitations associated with conventional solidification while maintaining superior dissolution performance. Therefore, it emerges as a promising alternative approach for enhancing the bioavailability of poorly water-soluble drugs. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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5 pages, 581 KiB  
Editorial
Research Progress on the Synthesis, Modification, and Applications of Microbial Biopolymers
by Shashi Kant Bhatia
Polymers 2025, 17(15), 2053; https://doi.org/10.3390/polym17152053 - 28 Jul 2025
Viewed by 258
Abstract
Microbe-based polymers are considered a suitable alternative to conventional petroleum-based polymers for various industrial applications such as packaging, drug delivery, and tissue engineering [...] Full article
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31 pages, 3024 KiB  
Review
Synthetic and Functional Engineering of Bacteriophages: Approaches for Tailored Bactericidal, Diagnostic, and Delivery Platforms
by Ola Alessa, Yoshifumi Aiba, Mahmoud Arbaah, Yuya Hidaka, Shinya Watanabe, Kazuhiko Miyanaga, Dhammika Leshan Wannigama and Longzhu Cui
Molecules 2025, 30(15), 3132; https://doi.org/10.3390/molecules30153132 - 25 Jul 2025
Viewed by 393
Abstract
Bacteriophages (phages), the most abundant biological entities on Earth, have long served as both model systems and therapeutic tools. Recent advances in synthetic biology and genetic engineering have revolutionized the capacity to tailor phages with enhanced functionality beyond their natural capabilities. This review [...] Read more.
Bacteriophages (phages), the most abundant biological entities on Earth, have long served as both model systems and therapeutic tools. Recent advances in synthetic biology and genetic engineering have revolutionized the capacity to tailor phages with enhanced functionality beyond their natural capabilities. This review outlines the current landscape of synthetic and functional engineering of phages, encompassing both in-vivo and in-vitro strategies. We describe in-vivo approaches such as phage recombineering systems, CRISPR-Cas-assisted editing, and bacterial retron-based methods, as well as synthetic assembly platforms including yeast-based artificial chromosomes, Gibson, Golden Gate, and iPac assemblies. In addition, we explore in-vitro rebooting using TXTL (transcription–translation) systems, which offer a flexible alternative to cell-based rebooting but are less effective for large genomes or structurally complex phages. Special focus is given to the design of customized phages for targeted applications, including host range expansion via receptor-binding protein modifications, delivery of antimicrobial proteins or CRISPR payloads, and the construction of biocontained, non-replicative capsid systems for safe clinical use. Through illustrative examples, we highlight how these technologies enable the transformation of phages into programmable bactericidal agents, precision diagnostic tools, and drug delivery vehicles. Together, these advances establish a powerful foundation for next-generation antimicrobial platforms and synthetic microbiology. Full article
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20 pages, 2108 KiB  
Article
Gelatin-Based Microspheres of Ciprofloxacin for Enhanced Lung Delivery and Biofilm Eradication in Pseudomonas aeruginosa Pulmonary Infections
by Luis Monrreal-Ortega, Rocío Iturriaga-Gallardo, Andrea Vilicic-Rubio, Pedro Torres, Patricio Leyton, Javier O. Morales, Tania F. Bahamondez-Canas and Daniel Moraga-Espinoza
Gels 2025, 11(8), 567; https://doi.org/10.3390/gels11080567 - 23 Jul 2025
Viewed by 312
Abstract
Chronic lung infection is the main predictor of morbidity and mortality in cystic fibrosis (CF), and current pharmacological alternatives are ineffective against Pseudomonas aeruginosa infections. We developed ciprofloxacin (CIP) for inhalation, aiming at improving its solubility through the formation of an amorphous solid [...] Read more.
Chronic lung infection is the main predictor of morbidity and mortality in cystic fibrosis (CF), and current pharmacological alternatives are ineffective against Pseudomonas aeruginosa infections. We developed ciprofloxacin (CIP) for inhalation, aiming at improving its solubility through the formation of an amorphous solid dispersion (ASD) using gelatin (GA). CIP and GA were dissolved in varying ratios and then spray-dried, obtaining CIP-GA microspheres in a single step. The dissolution rate, size distribution, morphology, and aerodynamic properties of CIP-GA microspheres were studied, as well as their antimicrobial activity on P. aeruginosa biofilms. Microspheres formulated with a higher GA ratio increased the dissolution of CIP ten-fold at 6 h compared to gelatin-free CIP. Formulations with 75% GA or more could form ASDs and improve CIP’s dissolution rate. CIP-GA microspheres outperformed CIP in eradicating P. aeruginosa biofilm at 24 h. The spray-drying process produced CIP-GA microspheres with good aerodynamic properties, as indicated by a fine particle fraction (FPF) of 67%, a D50 of 3.52 μm, and encapsulation efficiencies above 70%. Overall, this study demonstrates the potential of gelatin to enhance the solubility of poorly soluble drugs by forming ASDs. As an FDA-approved excipient for lung delivery, these findings are valuable for particle engineering and facilitating the rapid translation of technologies to the market. Full article
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14 pages, 1078 KiB  
Systematic Review
A Systematic Review of the Optilume® Drug-Coated Balloon in the Management of LUTS Secondary to BPH and Urethral Stricture
by Gaia Colalillo, Simona Ippoliti and Anastasios D. Asimakopoulos
Surgeries 2025, 6(3), 59; https://doi.org/10.3390/surgeries6030059 - 18 Jul 2025
Viewed by 432
Abstract
Background and Objective: Benign prostatic hyperplasia (BPH) and urethral stricture (US) are common causes of lower urinary tract symptoms in ageing men, often requiring repeated interventions. Conventional treatments of US, such as urethrotomy and mechanical dilation, have high recurrence rates. The Optilume drug-coated [...] Read more.
Background and Objective: Benign prostatic hyperplasia (BPH) and urethral stricture (US) are common causes of lower urinary tract symptoms in ageing men, often requiring repeated interventions. Conventional treatments of US, such as urethrotomy and mechanical dilation, have high recurrence rates. The Optilume drug-coated balloon catheter system, which combines mechanical dilation with paclitaxel delivery, has emerged as a minimally invasive alternative. This systematic review assesses its efficacy and safety in the management of BPH and US. Methods: A systematic search of PubMed was conducted for studies published between August 2020 and October 2023. Eligible studies included randomised controlled trials (RCTs), cohort studies, and case reports evaluating Optilume’s therapeutic effects. Key outcomes analysed included symptom relief, urinary flow improvement, recurrence rates, and adverse events. Results: Seven studies met the inclusion criteria, including five on US and two on BPH. The ROBUST trial series demonstrated sustained improvements in urinary flow rates and symptom scores in US patients over follow-up periods of up to four years. The EVEREST-1 and PINNACLE trials reported significant symptom relief and preserved sexual function in BPH patients, with a favourable safety profile and minimal complications. Conclusions: Optilume appears to be a promising alternative to conventional endoscopic treatments for US and BPH, offering durable symptom relief with a low complication rate. Further long-term studies are required to confirm its efficacy and cost-effectiveness in routine clinical practice. Full article
(This article belongs to the Special Issue Surgical Resection)
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29 pages, 1610 KiB  
Review
Tyrosine Kinase Inhibitors for Gastrointestinal Stromal Tumor After Imatinib Resistance
by Xian-Hao Xiao, Qian-Shi Zhang, Ji-Yuan Hu, Yin-Xu Zhang and He Song
Pharmaceutics 2025, 17(7), 923; https://doi.org/10.3390/pharmaceutics17070923 - 17 Jul 2025
Viewed by 516
Abstract
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by activating mutations in KIT (CD117) and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors (TKIs), especially imatinib, has significantly transformed GIST treatment. [...] Read more.
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract, primarily driven by activating mutations in KIT (CD117) and platelet-derived growth factor receptor alpha (PDGFRA). The introduction of tyrosine kinase inhibitors (TKIs), especially imatinib, has significantly transformed GIST treatment. However, the emergence of both primary and secondary resistance to imatinib presents ongoing therapeutic challenges. This review comprehensively explores the mechanisms underlying imatinib resistance and evaluates subsequent TKI therapies. Sunitinib, regorafenib, and ripretinib are currently approved as standard second-, third-, and fourth-line therapies, each demonstrating efficacy against distinct mutational profiles. Avapritinib, notably effective against PDGFRA D842V mutations, represents a milestone for previously untreatable subgroups. Several alternative agents—such as nilotinib, masitinib, sorafenib, dovitinib, pazopanib, and ponatinib—have shown varying degrees of success in refractory cases or specific genotypes. Investigational compounds, including crenolanib, bezuclastinib, famitinib, motesanib, midostaurin, IDRX-42, and olverembatinib, are under development to address resistant or wild-type GISTs. Despite progress, long-term efficacy remains limited due to evolving resistance. Future strategies include precision medicine approaches such as ctDNA-guided therapy, rational drug combinations, and novel drug delivery systems to optimize bioavailability and reduce toxicity. Ongoing research will be crucial for refining treatment sequencing and expanding therapeutic options, especially for rare GIST subtypes. Full article
(This article belongs to the Special Issue Kinase Inhibitor for Cancer Therapy, 2nd Edition)
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31 pages, 2314 KiB  
Review
Innovative Peptide Therapeutics in the Pipeline: Transforming Cancer Detection and Treatment
by Yanyamba Nsereko, Amy Armstrong, Fleur Coburn and Othman Al Musaimi
Int. J. Mol. Sci. 2025, 26(14), 6815; https://doi.org/10.3390/ijms26146815 - 16 Jul 2025
Viewed by 770
Abstract
Cancer remains a leading global health burden, profoundly affecting patient survival and quality of life. Current treatments—including chemotherapy, radiotherapy, immunotherapy, and surgery—are often limited by toxicity or insufficient specificity. Conventional chemotherapy, for instance, indiscriminately attacks rapidly dividing cells, causing severe side effects. In [...] Read more.
Cancer remains a leading global health burden, profoundly affecting patient survival and quality of life. Current treatments—including chemotherapy, radiotherapy, immunotherapy, and surgery—are often limited by toxicity or insufficient specificity. Conventional chemotherapy, for instance, indiscriminately attacks rapidly dividing cells, causing severe side effects. In contrast, peptide-based therapeutics offer a paradigm shift, combining high tumour-targeting precision with minimal off-target effects. Their low immunogenicity, multi-pathway modulation capabilities, and adaptability for diagnostics and therapy make them ideal candidates for advancing oncology care. Innovative peptide platforms now enable three transformative applications: (1) precision molecular diagnostics (e.g., 18F-PSMA-1007 for prostate cancer detection), (2) targeted therapies (e.g., BT5528 and SAR408701 targeting tumour-specific antigens), and (3) theranostic systems (e.g., RAYZ-8009 and 177Lu-FAP-2286 integrating imaging and radiotherapy). Despite their promise, peptides face challenges like metabolic instability and short half-lives. Recent advances in structural engineering (e.g., cyclization and D-amino acid incorporation) and delivery systems (e.g., nanoparticles and PEGylation) have significantly enhanced their clinical potential. This review highlights peptide-based agents in development, showcasing their ability to improve early cancer detection, reduce metastasis, and enhance therapeutic efficacy with fewer adverse effects. Examples like CLP002 underscore their role in personalised medicine. By overcoming current limitations, peptide drugs are poised to redefine cancer management, offering safer, more effective alternatives to conventional therapies. Their integration into clinical practice could mark a critical milestone in achieving precision oncology. Full article
(This article belongs to the Special Issue Peptides as Biochemical Tools and Modulators of Biological Activity)
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