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Search Results (295)

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22 pages, 1744 KB  
Review
From Circulation to Regeneration: Blood Cell Membrane-Coated Nanoparticles as Drug Delivery Platform for Immune-Regenerative Therapy
by Yun-A Kim, Min Hee Lee, Hee Su Sohn and Han Young Kim
Pharmaceutics 2026, 18(1), 66; https://doi.org/10.3390/pharmaceutics18010066 - 4 Jan 2026
Viewed by 268
Abstract
Cell membrane-coated nanoparticles represent a biomimetic drug delivery approach that integrates biological membrane functions with synthetic nanomaterials. Among the various membrane sources, those derived from blood cells such as red blood cells, platelets, and leukocytes offer distinctive advantages, including immune evasion, prolonged systemic [...] Read more.
Cell membrane-coated nanoparticles represent a biomimetic drug delivery approach that integrates biological membrane functions with synthetic nanomaterials. Among the various membrane sources, those derived from blood cells such as red blood cells, platelets, and leukocytes offer distinctive advantages, including immune evasion, prolonged systemic circulation, and selective tissue targeting. These properties collectively enable efficient and biocompatible delivery of therapeutic agents to diseased tissues, minimizing off-target effects and systemic toxicity. This review focuses on blood cell membrane-derived nanocarriers as drug delivery and immune-regenerative platforms, in which membrane-mediated immunomodulation synergizes with therapeutic payloads to address inflammatory or degenerative pathology. We discuss recent advances in blood cell membrane coating technologies, including membrane isolation, nanoparticle core selection, fabrication techniques, and the development of hybrid and engineered membrane systems that enhance therapeutic efficacy through integrated immune regulation and localized drug action. To illustrate these advances, we also compile membrane type-specific nanocarrier systems, summarizing their core nanoparticle designs, coating strategies, therapeutic cargoes, and associated disease models. Challenges related to biological source variability, scalability, safety, and regulatory standardization remain important considerations for clinical translation. In this review we systematically address these issues and discuss emerging solutions and design strategies aimed at advancing blood cell membrane-based nanocarriers toward clinically viable immune-regenerative therapies. Full article
(This article belongs to the Special Issue Cell-Mediated Delivery Systems)
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22 pages, 4387 KB  
Article
The Optimal Amount of PAMAM G3 Dendrimer in Polyurethane Matrices Makes Them a Promising Tool for Controlled Drug Release
by Magdalena Zaręba, Magdalena Zuzanna Twardowska, Paweł Błoniarz, Jaromir B. Lechowicz, Jakub Czechowicz, Dawid Łysik, Magdalena Rzepna and Łukasz Stanisław Uram
Polymers 2026, 18(1), 135; https://doi.org/10.3390/polym18010135 - 1 Jan 2026
Viewed by 347
Abstract
Systemic anticancer therapy causes a number of side effects; therefore, local drug release devices may play an important role in this area. In this study, we developed polyurethane-dendrimer foams containing different amounts of third-generation poly (amidoamine) dendrimers (PAMAM G3) to evaluate their ability [...] Read more.
Systemic anticancer therapy causes a number of side effects; therefore, local drug release devices may play an important role in this area. In this study, we developed polyurethane-dendrimer foams containing different amounts of third-generation poly (amidoamine) dendrimers (PAMAM G3) to evaluate their ability to encapsulate and release the model anticancer drug doxorubicin (DOX), as well as their biocompatibility and effectiveness against normal and cancer cells in vitro. PU–PAMAM foams containing 10–50 wt% PAMAM G3 were prepared using glycerin-based polyether polyol and castor oil as co-components. Structural and rheological analyses revealed that foams containing up to 20 wt% PAMAM G3 exhibited a well-developed porous structure, while higher dendrimer loadings (≥30 wt%) led to irregular cell shapes, pore coalescence, and thinning of cell walls, and indicated a gradual loss of structural integrity. Rheological creep–recovery measurements confirmed the structural findings: moderate PAMAM G3 incorporation (≤20 wt%) increased both the instantaneous and delayed elastic modulus (E1 ≈ 130–140 kPa; E2 ≈ 80 kPa) and enhanced elastic recovery, reflecting improved cross-link density and foam stability. Higher dendrimer contents (30–50 wt%) caused a decline in these parameters and higher viscoelastic compliance, indicating a softer, less stable structure. The DOX loading capacity and encapsulation efficiency increased with PAMAM G3 content, reaching maximum values of 35% and 51% for 30–40 wt% PAMAM G3, respectively. However, the most sustained DOX release profiles were observed for matrices containing 20 wt% PAMAM G3. Analysis of cumulative release and kinetic modeling revealed a transition from diffusion-controlled release at low PAMAM contents to burst-dominated release at higher dendrimer loadings. Importantly, matrices containing 10–20 wt% PAMAM G3 also indicated selective anticancer action against squamous cell carcinoma (SCC-15) compared to non-cancerous human keratinocytes (HaCaT). Moreover, the DOX they released effectively destroyed cancer cells. Overall, PU–PAMAM foams containing 10–20 wt% PAMAM G3 provide the most balanced combination of structural stability, controlled drug release, and cytocompatibility. These materials therefore represent a promising platform as passive carriers in drug delivery systems (DDSs), such as local implants, anticancer patches, or bioactive wound dressings. Full article
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34 pages, 786 KB  
Review
Current State of the Neurotrophin-Based Pharmaceutics in the Treatment of Neurodegenerative Diseases and Neuroinflammation
by Tatiana A. Fedotcheva and Nikolay L. Shimanovsky
Med. Sci. 2026, 14(1), 15; https://doi.org/10.3390/medsci14010015 - 29 Dec 2025
Viewed by 375
Abstract
Background: The regulation of the synthesis of the nerve growth factor and other neurotrophins is one of the dynamically developing areas of pharmacotherapy of neurological and mental disorders. Despite a large number of studies of various ligands of neurotrophin receptors, only a few [...] Read more.
Background: The regulation of the synthesis of the nerve growth factor and other neurotrophins is one of the dynamically developing areas of pharmacotherapy of neurological and mental disorders. Despite a large number of studies of various ligands of neurotrophin receptors, only a few have reached clinical application and only for ocular diseases. The aim of this narrative review was to systematize the main progress on neurotrophin-based pharmaceutics; to perform a comparative critical analysis of various therapeutic strategies, elucidate the underlying causes of clinical trial failures, and identify the most promising avenues for future development. Methods: The literature search was conducted in PubMed, Google Scholar, Medline, and EBSCO, and the ClinicalTrials.gov database was used to track current clinical studies, along with the official websites of pharmaceutical companies. The search covered original studies published up to October 2025, with inclusion restricted to articles published in English. Articles describing specific pharmacological compounds that had reached the clinical trial stage were selected. Foundational biological research was referenced to contextually explain the mechanisms of action of the drugs and their therapeutic implications. Results: Recombinant neurotrophins and synthetic molecules, the agonists and antagonists of their receptors, and cell-based gene therapy are promising means for the prevention and rehabilitation of ischemic conditions, as well as the treatment of neuropathic pain and neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Some of these have undergone clinical trials, yet only neurotrophins for ocular diseases have been implemented in clinical practice: recombinant NGF—cenegermin and recombinant CNTF—Revakinagene taroretcel. The success of these eye drugs is likely attributable to their local administration, improved bioavailability, and low ocular immunoresistance. Conclusions: The study identified limitations and future prospects for neurotrophin-based pharmaceuticals. For future clinical trials, attention should be paid to the pharmacogenetic profiles of the patients and the evaluation of the inflammatory status of the disease. Novel plasma biomarkers of the effectiveness are needed as well as TSPO-PET imaging. Drug delivery systems remain insufficient; therefore, efforts should focus on inducing endogenous neurotrophin production and developing highly selective agonists and antagonists of neurotrophin receptors. It is crucial to establish a favorable premorbid background before neurotrophin therapy to minimize immunoresistance. Full article
(This article belongs to the Collection Advances in the Pathogenesis of Neurodegenerative Diseases)
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29 pages, 2541 KB  
Review
Recent Advances in pH-Responsive Coatings for Orthopedic and Dental Implants: Tackling Infection and Inflammation and Enhancing Bone Regeneration
by Reyhaneh Gholami, Naser Valipour Motlagh, Zahra Yousefi, Fahimeh Gholami, Joseph J. Richardson, Behnam Akhavan, Vahid Adibnia and Vi Khanh Truong
Coatings 2025, 15(12), 1471; https://doi.org/10.3390/coatings15121471 - 12 Dec 2025
Viewed by 663
Abstract
Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant [...] Read more.
Bone is a structurally complex and dynamic tissue that plays a crucial role in mobility and skeletal stability. However, conditions such as osteoporosis, osteoarthritis, trauma-induced fractures, infections, and malignancies often necessitate the use of orthopedic and dental implants. Despite significant progress in implant biomaterials, challenges such as bacterial infection, inflammation, and loosening continue to compromise implant longevity, frequently leading to revision surgeries and extended recovery times. Smart coatings have emerged as a next-generation solution to these problems by providing on-demand, localized therapeutic responses to microenvironmental changes around implants and promoting bone regeneration. Such coatings can minimize antibiotic resistance by enabling controlled, stimulus-triggered drug release. Although the idea of using pH-sensitivity as a tool to make smart coatings is not a new thought, there are no options currently good enough to enter clinical studies. This review provides a comprehensive overview of recent advances in pH-sensitive polymers, hybrid composites, porous architectures, and bioactive linkers designed to dynamically respond to pathological pH variations at implant sites. By investigating the mechanisms of action, antibacterial and anti-inflammatory effects, and roles in bone regeneration, it is shown that the ability to provide time-dependent drug release for both short-term and long-term infections, as well as keeping the environment welcoming to the bone cell growth and replacement, is not an easy goal to reach, even with a fully biocompatable, non-toxic, and semi-biodegradable (one that releases the drug, but does not fade away) coating material compound. Reviewing all available options, including their functions and failures, finally, emerging trends, translational barriers, and future opportunities for clinical implementation are highlighted, underscoring the transformative potential of bioresponsive coatings in orthopedic and dental implant technologies. Full article
(This article belongs to the Special Issue Surface Engineering of Bone Implants)
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35 pages, 2326 KB  
Review
Nanomaterials for Photocatalytic Inactivation and Eradication of Candida spp. Biofilms in Healthcare Environment: A Novel Approach in Modern Clinical Practice
by Karolina Kraus, Paweł Mikziński, Jarosław Widelski and Emil Paluch
Molecules 2025, 30(23), 4500; https://doi.org/10.3390/molecules30234500 - 21 Nov 2025
Viewed by 636
Abstract
Modern medicine is facing a significant challenge in dealing with infections caused by Candida spp. and the biofilms they form. Although there are numerous treatment methods available for Candida species, standard therapeutic protocols are increasingly failing, particularly in cases of chronic local infections, [...] Read more.
Modern medicine is facing a significant challenge in dealing with infections caused by Candida spp. and the biofilms they form. Although there are numerous treatment methods available for Candida species, standard therapeutic protocols are increasingly failing, particularly in cases of chronic local infections, such as those affecting immunocompromised patients (e.g., due to immunosuppression or diabetes). In such cases, a promising approach is to use nanomaterials to inactivate and eradicate Candida spp. and their biofilms. In order to limit the spread of Candida spp. and their biofilms within the healthcare environment, thereby reducing the risk of patient infection, photocatalysis appears to be a noteworthy method for improving therapeutic outcomes. Candida spp. biofilms are difficult to eradicate because they possess multiple resistance mechanisms—including protective extracellular matrix, efflux pumps, quorum sensing, persister and Goliath cells—which collectively enhance drug tolerance, adhesion, and survival rates under antifungal treatment. The use of nanomaterials, such as nanoparticles, carbon dots, or nanozymes for photocatalytic processes, seems to be a promising solution, showing outstanding results in Candida spp. biofilm disruption and inactivation. This is due to their superior biofilm penetration, effective destruction of proteins and enzymes, destabilization of EPS, degradation of nucleic acids, and reduced drug resistance. We collected the most important nanomaterials useful in combating Candida spp. biofilm and organized the photocatalysis mechanism of action in its disruption. Based on current research, we have compiled modern strategies involving nanomaterials and their photocatalytic activity for potential application in the healthcare environment, with the aim of reducing the presence of Candida spp. biofilms and, consequently, lowering the incidence of Candida spp.-related infections. Full article
(This article belongs to the Special Issue Novel Nanomaterials for Photocatalysis)
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48 pages, 3373 KB  
Review
Nanotechnology Driven Innovations in Modern Pharmaceutics: Therapeutics, Imaging, and Regeneration
by Nargish Parvin, Mohammad Aslam, Md Najib Alam and Tapas K. Mandal
Nanomaterials 2025, 15(22), 1733; https://doi.org/10.3390/nano15221733 - 17 Nov 2025
Cited by 2 | Viewed by 1499
Abstract
The integration of smart nanomaterials into pharmaceutics has transformed approaches to disease diagnosis, targeted therapy, and tissue regeneration. These nanoscale materials exhibit unique features such as controlled responsiveness, biocompatibility, and precise site-specific action, offering new possibilities for personalized healthcare. This review provides a [...] Read more.
The integration of smart nanomaterials into pharmaceutics has transformed approaches to disease diagnosis, targeted therapy, and tissue regeneration. These nanoscale materials exhibit unique features such as controlled responsiveness, biocompatibility, and precise site-specific action, offering new possibilities for personalized healthcare. This review provides a comprehensive overview of recent advances in the design and application of functional nanomaterials, including nanoparticle-based drug carriers, responsive hydrogels, and nanostructured scaffolds. Special focus is placed on stimuli-triggered systems that achieve controlled drug release and localized therapeutic effects. In addition, the review explores how these materials enhance diagnostic imaging and support tissue regeneration through adaptive and multifunctional designs. Importantly, this work uniquely integrates stimuli-responsive nanomaterials across therapeutic, imaging, and regenerative domains, providing a unified view of their biomedical potential. The challenges of clinical translation, large-scale synthesis, and regulatory approval are critically analyzed to outline future directions for research and real-world implementation. Overall, this review highlights the pivotal role of smart nanomaterials in advancing modern pharmaceutics toward more effective and patient-centered therapies. Full article
(This article belongs to the Section Biology and Medicines)
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20 pages, 2984 KB  
Article
Engineered Fenretinide- and Tocilizumab-Releasing Janus Nanoparticles for Site-Directed Immunochemoprevention of Squamous Cell Carcinoma of the Lung
by Daren Wang, Albert Chang, Fortune Shea, Yifei He, Richard Spinney, Jonathan D. Whitsett, Joerg Lahann and Susan R. Mallery
Pharmaceutics 2025, 17(11), 1471; https://doi.org/10.3390/pharmaceutics17111471 - 14 Nov 2025
Viewed by 626
Abstract
Background: Both clinical and research data support the contribution of IL6-mediated local immunosuppression coupled with IL6-initiated protumorigenic processes, e.g., sustained proliferation and angiogenesis in the development of many cancers, including lung cancer. By virtue of their pharmacologic advantage, controlled release, local delivery [...] Read more.
Background: Both clinical and research data support the contribution of IL6-mediated local immunosuppression coupled with IL6-initiated protumorigenic processes, e.g., sustained proliferation and angiogenesis in the development of many cancers, including lung cancer. By virtue of their pharmacologic advantage, controlled release, local delivery formulations can provide immunochemopreventive relevant agent levels at the target site with negligible systemic agent-related effects. Bioavailability is a major challenge with chemopreventive agents. Methods: Janus nanoparticles (JNPs), however, are a versatile drug delivery platform that addresses several major cancer preventive challenges including bioavailability and retention of bioactivity, with elimination of potential deleterious effects with systemic administration. Furthermore, JNPs feature two discrete compartments that enable concurrent delivery of two chemically distinct agents with complementary mechanisms of action. Results: Our data show that the synthetic vitamin A derivative, fenretinide (4HPR), and the IL6R inhibitor, tocilizumab (TCZ), inhibit pathways integral for the development of lung cancer. Initial molecular modeling and kinase activity assays confirmed that 4HPR serves as a competitive inhibitor for active-site ATP binding of two key IL6 downstream kinases (JAK1, CK2). Concurrent RNA-seq analyses that employed Qiagen Ingenuity Pathway Analysis showed significant inhibition of canonical pathways associated with DNA replication and division in conjunction with significant activation of immunogeneic cell death and TREM 1 signaling pathways and showed the immune-augmenting, cancer-preventive impact of 4HPR-TCZ treatment on gene expression in premalignant lung epithelial cells. Subsequent qRT-PCR analyses corroborated the RNA seq findings and demonstrated 3- to 6-fold increased expression of TREM 1 and immunogenic cell death genes, such as TREM1 and NLRC4 and HSPA6 and DDTT3, respectively. These data collectively guided the development of human serum albumin–chitosan JNPs for the co-delivery of 4HPR and TCZ, respectively. 4HPR-TCZ JNP characterization studies demonstrated high circularities and stability in suspension, as shown by consistency in diameter and minimal changes to the polydispersity index, while confocal microscopy confirmed their biocompartmental nature. Subsequent tertiary chemoprevention in vivo studies that employed a highly aggressive human lung cancer cell line showed that JNPs releasing 4HPR and 4HPR-TCZ significantly reduced tumor volume, as assessed by vital tumor tissue, suppressed proliferation, increased apoptosis, and promoted intratumor vascular instability. Conclusions: Collectively, these studies elucidate 4HPR-TCZ in vitro chemopreventive mechanisms of action and demonstrate proof of concept for JNP-4HPR-TCZ in vivo efficacy. Full article
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20 pages, 2912 KB  
Review
Molecular Mechanisms of Wound Healing: The Role of Medicinal Plants
by Merlin Esad, Ivica Dimov, Mariya Choneva, Mihaela Popova, Vesela Kokova, Elisaveta Apostolova and Anelia Bivolarska
Life 2025, 15(11), 1748; https://doi.org/10.3390/life15111748 - 14 Nov 2025
Cited by 1 | Viewed by 1673
Abstract
Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, [...] Read more.
Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, and tissue repair. Medicinal plants and their bioactive compounds, such as flavonoids, alkaloids, tannins, and other phytoconstituents, have demonstrated significant anti-inflammatory, antioxidant, and immunomodulatory effects that modulate these pathways. Tannins contribute to repair through neutralization of reactive oxygen species (ROS), activation of antioxidant enzymes, and metal-chelating activity. Alkaloids, including tetrandrine, oxymatrine, and berberine, inhibit NF-κB signaling, thereby reducing pro-inflammatory cytokines such as IL-1β and TNF-α. Flavonoids regulate inflammatory mediators and enzymes, including COX and phospholipase A2, while also protecting against oxidative stress and stimulating fibroblast and keratinocyte proliferation—key steps in tissue regeneration. Collectively, these compounds accelerate wound closure by reducing oxidative stress and promoting cellular proliferation and migration. Thus, medicinal plants represent promising complementary approaches to wound management. Future research should focus on developing advanced drug delivery systems to enhance the stability, bioavailability, and targeted action of plant-derived compounds. Localized and biomaterial-based strategies show promise for sustained release at the wound site, and further preclinical and clinical studies are required to ensure their safety, reproducibility, and efficacy. Full article
(This article belongs to the Section Pharmaceutical Science)
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18 pages, 8857 KB  
Article
Biomimetic Porous Coatings on a Biocompatible Ti-15Mo Alloy as a Platform for Local Delivery of Anticancer Drugs to Patient Tissues
by Svetlana Gatina, Ruzil Farrakhov, Alfiz Gareev, Azat Sabitov, Nariman A. Enikeev, Natalia Anisimova and Mikhail Kiselevskiy
Biomedicines 2025, 13(11), 2779; https://doi.org/10.3390/biomedicines13112779 - 14 Nov 2025
Viewed by 532
Abstract
Background and Objectives: Currently, the development of local drug delivery systems for the treatment of cancer patients is a pressing issue. Such systems allow for the targeted delivery of anticancer drugs directly to the tumor site, ensuring prolonged drug release or reducing the [...] Read more.
Background and Objectives: Currently, the development of local drug delivery systems for the treatment of cancer patients is a pressing issue. Such systems allow for the targeted delivery of anticancer drugs directly to the tumor site, ensuring prolonged drug release or reducing the risk of recurrence after tumor removal, minimizing the impact on healthy tissues and thereby reducing the overall toxic load on the body. This work is devoted to evaluating the prospects of using scaffolds based on low-modulus titanium Ti-15Mo alloy with a biomimetic coating as a platform for the local administration of the cytostatic drug cisplatin into the patient’s body. Methods: Porous coatings were obtained by plasma electrolytic oxidation in an aqueous solution of sodium phosphate and calcium acetate with the addition of various components. The influence of coating parameters on the corrosion resistance of samples and on the antiproliferative effect of cisplatin-loaded scaffolds was evaluated. Human K562 hemoblastosis, HT116 intestinal cancer, and SKOV3 ovarian cancer cell lines were used as cell models. Results: It was shown that the addition of sodium phosphate (the PS type electrolyte) provides the formation of a coating with a developed system of interconnected pores characterized by an attractive combination of parameters: high porosity (17%), high pore size (3.9 μm), and considerable thickness (17.4 μm). This coating demonstrated the best corrosion resistance in a Ringer solution as compared to the other tested states. In addition, the PS coating loaded with cisplatin exhibited a pronounced cytotoxic effect on cancer cells. This effect was attributed to its ability to fix cisplatin on the surface, which slows down its release into the extracellular environment, increasing the time of its action, thereby contributing to a more effective (by more than 3 times) suppression of tumor cell proliferation compared to the action of the standard form of the drug in the form of a solution when changing the growth medium and subsequent incubation for 48 h. Conclusions: PS scaffolds made of low-modulus titanium alloy Ti-15Mo with a biomimetic surface in an electrolyte based on an aqueous solution of sodium phosphate and calcium acetate with the addition of sodium silicate can be used as an advanced platform for the local delivery of the cytostatic drug cisplatin, which makes them promising for application in orthopedic oncology. Full article
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20 pages, 854 KB  
Review
Nanotechnology-Based Delivery Systems and Retinal Pigment Epithelium: Advances, Targeting Approaches, and Translational Challenges
by Michele Nardella, Marco Pellegrini, Angeli Christy Yu, Ginevra Giovanna Adamo, Marco Mura and Massimo Busin
Biomolecules 2025, 15(11), 1592; https://doi.org/10.3390/biom15111592 - 13 Nov 2025
Viewed by 1112
Abstract
The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly [...] Read more.
The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application. Full article
(This article belongs to the Special Issue State of the Art and Perspectives in Retinal Pigment Epithelium)
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21 pages, 524 KB  
Review
Mechanistic Insights into the Anti-Inflammatory and Anti-Proliferative Effects of Selected Medicinal Plants in Endometriosis
by Oliwia Burdan, Natalia Picheta, Julia Piekarz, Karolina Daniłowska, Filip Gajewski, Krzysztof Kułak and Rafał Tarkowski
Int. J. Mol. Sci. 2025, 26(22), 10947; https://doi.org/10.3390/ijms262210947 - 12 Nov 2025
Viewed by 1493
Abstract
Endometriosis involves oestrogen-dependent chronic inflammation and the abnormal proliferation of ectopic endometrial tissue. Conventional hormonal therapies suppress systemic oestrogen, but do not fully address local oxidative and inflammatory signalling. This review provides a mechanistic synthesis of recent molecular evidence. This evidence is on [...] Read more.
Endometriosis involves oestrogen-dependent chronic inflammation and the abnormal proliferation of ectopic endometrial tissue. Conventional hormonal therapies suppress systemic oestrogen, but do not fully address local oxidative and inflammatory signalling. This review provides a mechanistic synthesis of recent molecular evidence. This evidence is on four FDA-recognized (Food and Drug Administration) medicinal plants. These are Curcuma longa, Zingiber officinale, Glycyrrhiza glabra, and Silybum marianum. The review highlights their capacity to modulate key intracellular pathways. These pathways are implicated in endometriosis. The review covers the integration of phytochemical-specific actions within NF-κB- (nuclear factor kappa-light-chain-enhancer of activated B cells), COX-2-(Cyclooxygenase-2), PI3K/Akt-(PI3K/Akt signaling pathway), Nrf2/ARE-(Nuclear factor erythroid 2–related factor 2) and ERβ-(Estrogen receptor beta) mediated networks, which jointly regulate cytokine secretion, apoptosis, angiogenesis and redox balance in endometrial lesions. Curcumin downregulates COX-2 and aromatase while activating Nrf2 signalling, shogaol from ginger suppresses prostaglandin synthesis and induces caspase-dependent apoptosis, isoliquiritigenin from liquorice inhibits HMGB1-TLR4–NF-κB (High Mobility Group Box 1, Toll-like receptor 4) activation, and silymarin from milk thistle reduces IL-6 (Interleukin-6) and miR-155 (microRNA-155) expression while enhancing antioxidant capacity. Together, these phytochemicals demonstrate pharmacodynamic complementarity with hormonal agents by targeting local inflammatory and oxidative circuits rather than systemic endocrine axes. This mechanistic framework supports the rational integration of phytotherapy into endometriosis management and identifies redox-inflammatory signalling nodes as future translational targets. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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19 pages, 536 KB  
Review
The Origins and Genetic Diversity of HIV-1: Evolutionary Insights and Global Health Perspectives
by Ivailo Alexiev and Reneta Dimitrova
Int. J. Mol. Sci. 2025, 26(22), 10909; https://doi.org/10.3390/ijms262210909 - 11 Nov 2025
Viewed by 3146
Abstract
Human immunodeficiency virus (HIV), comprising two distinct types, HIV-1 and HIV-2, remains one of the most significant global health challenges, originating from multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) in the early 20th century. This review traces the evolutionary trajectory of HIV [...] Read more.
Human immunodeficiency virus (HIV), comprising two distinct types, HIV-1 and HIV-2, remains one of the most significant global health challenges, originating from multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) in the early 20th century. This review traces the evolutionary trajectory of HIV from zoonotic spillover to its establishment as a global pandemic. HIV-1, the principal strain responsible for AIDS, emerged from SIVcpz in Central African chimpanzees, with phylogenetic evidence indicating initial human transmission between the 1920s and 1940s in present day Democratic Republic of Congo. The virus disseminated through colonial trade networks, reaching the Caribbean by the 1960s before establishing endemic transmission in North America and Europe. HIV’s extraordinary genetic diversity—driven by high mutation rates (~10−5 mutations per base per replication cycle) and frequent recombination events—has generated multiple groups, subtypes, and circulating recombinant forms (CRFs) with distinct epidemiological patterns. HIV-1 Group M, comprising subtypes A through L, accounts for over 95% of global infections, with subtype C predominating in sub-Saharan Africa and Asia, while subtype B dominates in Western Europe and North America. The extensive genetic heterogeneity of HIV significantly impacts diagnostic accuracy, antiretroviral therapy efficacy, and vaccine development, as subtypes exhibit differential biological properties, transmission efficiencies, and drug resistance profiles. Contemporary advances, including next-generation sequencing (NGS) for surveillance, broadly neutralizing antibodies for cross-subtype prevention and therapy, and long-acting antiretroviral formulations to improve adherence, have transformed HIV management and prevention strategies. NGS enables near real-time surveillance of drug resistance mutations and inference of transmission networks where it is available, although access and routine application remain uneven across regions. Broadly neutralizing antibodies demonstrate cross-subtype efficacy, while long-acting formulations have the potential to improve treatment adherence. This review synthesizes recent evidence and offers actionable recommendations to optimize clinical and public health responses—including the routine use of genotypic resistance testing where feasible, targeted use of phylogenetic analysis for outbreak investigation, and the development of region-specific diagnostic and treatment algorithms informed by local subtype prevalence. While the understanding of HIV’s evolutionary dynamics has substantially improved and remains essential, translating this knowledge into universally implemented intervention strategies remains a key challenge for achieving the UNAIDS 95-95-95 targets and the goal of ending AIDS as a public health threat by 2030. Full article
(This article belongs to the Section Molecular Microbiology)
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26 pages, 1485 KB  
Review
Morphological Correlates of TRPV1 Agonist-Induced Activation and Defunctionalization of Nociceptor Neurons
by Gábor Jancsó, Mária Dux and Péter Sántha
Int. J. Mol. Sci. 2025, 26(21), 10350; https://doi.org/10.3390/ijms262110350 - 24 Oct 2025
Viewed by 1359
Abstract
Transient receptor potential vanilloid type 1 (TRPV1) agonist-induced analgesia is a current hot topic of pain research and a promising possibility to alleviate chronic/neuropathic pain. Local applications in humans and animals and systemic administration in experimental animals of TRPV1 agonists have been demonstrated [...] Read more.
Transient receptor potential vanilloid type 1 (TRPV1) agonist-induced analgesia is a current hot topic of pain research and a promising possibility to alleviate chronic/neuropathic pain. Local applications in humans and animals and systemic administration in experimental animals of TRPV1 agonists have been demonstrated to produce a long-lasting blockade of nociceptors leaving the function of other types of sensory nerves, as well as autonomic and motor nerve fibers, intact. Morphological studies revealed that TRPV1 agonist-mediated drug action is linked to distinct structural alterations involving reversible and/or irreversible neuronal degenerative processes. This review is intended to summarize the available information on morphological changes associated with TRPV1 agonist-induced activation and defunctionalization of nociceptors expressing the TRPV1/capsaicin receptor. In addition, morphological alterations associated with some pathologies involving TRPV1-expressing nociceptors will also be dealt with. Activation and defunctionalization can be elicited from any domain of TRPV1 receptor-expressing neurons. Considering the similar membrane properties of perikarya, axons and peripheral receptive nerve endings, the term chemosensitive nociceptor neuron is proposed to denote this particular class of primary sensory neurons. Full article
(This article belongs to the Special Issue TRP Channels for Pain, Itch and Inflammation Relief: 2nd Edition)
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29 pages, 3223 KB  
Article
Injectable In Situ Thermoreversible Gel Depot System of Lidocaine Nanoemulsion for Prolonged Anesthetic Activity in Dental and Operative Procedures
by Shery Jacob, Fathima Sheik Kather, Shakta Mani Satyam, Sai H. S. Boddu, Firas Assaf, Tasnem H. Abdelfattah Allam and Anroop B. Nair
Pharmaceutics 2025, 17(10), 1355; https://doi.org/10.3390/pharmaceutics17101355 - 20 Oct 2025
Cited by 1 | Viewed by 1388
Abstract
Background/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit [...] Read more.
Background/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit patient compliance and procedural efficiency. This study aimed to develop and evaluate a novel injectable nanoemulsion-based in situ gel depot system of LD to provide prolonged anesthetic activity. Methods: LD-loaded nanoemulsions were formulated by high-shear homogenization followed by probe sonication, employing Miglyol 812 N (oil phase), a combination of Tween 80 and soy lecithin (surfactant–co-surfactant), glycerin, and deionized water (aqueous phase). The selected nanoemulsion (S1) was dispersed in a thermoreversible poloxamer solution to form a nanoemulgel. The preparation was evaluated for globule diameter and uniformity, zeta potential, surface morphology, pH, drug content, stability, rheological behavior, injectability, and in vitro drug release. Analgesic efficacy was assessed via tail-flick and thermal paw withdrawal latency tests in Wistar rats. Cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements. Results: The developed nanoemulsions demonstrated a spherical shape, nanometer size (206 nm), high zeta-potential (−66.67 mV) and uniform size distribution, with a polydispersity index of approximately 0.40, while the nanoemulgel demonstrated appropriate thixotropic properties for parenteral administration. In vitro release profiles showed steady LD release (5 h), following the Higuchi model. In vivo studies showed significantly prolonged analgesic effects lasting up to 150 min (2.5 h) compared to standard LD-HCl injection (p < 0.001), with no adverse cardiovascular effects observed. Conclusions: The developed injectable LD in situ nanoemulgel offers a promising, patient-friendly alternative for prolonged anesthetic delivery in dental and operative procedures, potentially reducing the need for repeated injections and enhancing procedural comfort. Full article
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15 pages, 3340 KB  
Article
Antifungal Drug Efficacy Profiles Against Vaginal Candida albicans: A Multi-Drug Comparative Analysis
by Mohammad Zubair and Yazeed Albalawi
J. Clin. Med. 2025, 14(20), 7266; https://doi.org/10.3390/jcm14207266 - 15 Oct 2025
Viewed by 2596
Abstract
Background: Candida albicans infects most reproductive-aged women, causing a prevalent infection known as Vulvovaginal Candida. As there has been an increase in resistance to widely used antifungal agents, particularly fluconazole, used in infections, local susceptibility profiles are needed to inform treatment [...] Read more.
Background: Candida albicans infects most reproductive-aged women, causing a prevalent infection known as Vulvovaginal Candida. As there has been an increase in resistance to widely used antifungal agents, particularly fluconazole, used in infections, local susceptibility profiles are needed to inform treatment options. Methods: This comparative observational study was carried out to determine the in vitro susceptibility of six antifungal compounds [fluconazole, voriconazole, itraconazole, ketoconazole, nystatin, and amphotericin B] to 163 vaginal Candida albicans isolates obtained in three hospitals in Tabuk, Saudi Arabia. MIC50, MIC90, and MFC values were calculated in Broth microdilution tests according to the standards of CLSI M27-A3. Friedman and Wilcoxon signed-rank tests were used to carry out statistical analysis. Results: It was observed that Amphotericin B and itraconazole recorded the lowest MIC and MFC, revealing better antifungal action. The worst performer was fluconazole with MIC50 (13.79 μg/mL), MIC90 (27.59 μg/mL), and MFC (37.93 μg/mL), and 85% resistance. It was found that there are significant differences between antifungal agents (p < 0.001), and amphotericin B and itraconazole always performed best compared to fluconazole and voriconazole. Conclusions: The results shows antifungal effectiveness as Amphotericin B and itraconazole are the most effective against vaginal Candida albicans isolates. There is a high rate of resistance to fluconazole, suggesting it should no longer be the first choice of treatment in this area. These findings highlight the need for local monitoring of drug resistance to guide treatment choices and emphasize the importance of using antifungals properly to prevent increased resistance. Full article
(This article belongs to the Section Pharmacology)
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