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Search Results (385)

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Keywords = pH-controlled drug delivery systems

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46 pages, 1696 KB  
Review
Niosomes as Vesicular Carriers: From Formulation Strategies to Stimuli-Responsive Innovative Modulations for Targeted Drug Delivery
by Andra Ababei-Bobu, Bianca-Ștefania Profire, Andreea-Teodora Iacob, Oana-Maria Chirliu, Florentina Geanina Lupașcu and Lenuța Profire
Pharmaceutics 2025, 17(11), 1473; https://doi.org/10.3390/pharmaceutics17111473 - 14 Nov 2025
Abstract
Niosomes (NIOs), a class of nanovesicular drug delivery system, have garnered significant attention due to their unique architecture, resulting from the self-assembly of non-ionic surfactants (with or without cholesterol) in aqueous media. This bilayered structure enables the encapsulation of both hydrophilic agents in [...] Read more.
Niosomes (NIOs), a class of nanovesicular drug delivery system, have garnered significant attention due to their unique architecture, resulting from the self-assembly of non-ionic surfactants (with or without cholesterol) in aqueous media. This bilayered structure enables the encapsulation of both hydrophilic agents in the aqueous core and lipophilic compounds within the lipid bilayer, offering remarkable versatility in therapeutic applications. This article provides an overview of the key principles underlying niosomal formulations, including their composition, preparation methods, formulation conditions and the critical physicochemical parameters influencing vesicle formation and performance. Special emphasis is placed on recent innovations in surface and content modifications that have led to the development of stimuli-responsive niosomal systems, with precise and controlled drug release. These smart carriers are designed to respond to endogenous stimuli (such as pH variations, redox gradients, enzymatic activity, or local temperature changes in pathological sites), as well as to exogenous triggers (including light, ultrasound, magnetic or electric fields, and externally applied hyperthermia), thereby enhancing therapeutic precision. These surface and content modulation strategies effectively transform conventional NIOs into intelligent, stimuli-responsive platforms, reinforcing their innovative role in drug delivery and highlighting their significant potential in the development of smart nanomedicine. Full article
21 pages, 4278 KB  
Review
Recent Advances in Multimodal Nanostructured Bioaerogels for Smart Drug Delivery
by Muhanad A. Abdulsamad, Lujin A. Essa, Rabia Alghazeer, Norah Alkhayyal, Rawan Altalhi, Randah Alghamdi and Esam Bashir Yahya
Polymers 2025, 17(22), 3012; https://doi.org/10.3390/polym17223012 - 12 Nov 2025
Viewed by 147
Abstract
The convergence of nanotechnology and bioaerogels has paved the way for the development of multimodal nanostructured bioaerogels with remarkable potential in smart drug delivery systems. These advanced biomaterials integrate multiple functionalities, including sensing, targeting, and therapeutic actions, to enhance drug efficacy, minimize systemic [...] Read more.
The convergence of nanotechnology and bioaerogels has paved the way for the development of multimodal nanostructured bioaerogels with remarkable potential in smart drug delivery systems. These advanced biomaterials integrate multiple functionalities, including sensing, targeting, and therapeutic actions, to enhance drug efficacy, minimize systemic side effects, and enable real-time monitoring of therapeutic responses. This review provides a comprehensive analysis of the structural design, physicochemical properties, and fabrication strategies of multimodal bioaerogels. It further explores their role in responsive drug delivery, emphasizing stimuli-responsive mechanisms such as pH, temperature, and enzymatic triggers. The incorporation of nanomaterials, including metallic nanoparticles, carbon-based nanostructures, and polymeric nanocarriers, has endowed bioaerogels with tunable porosity, controlled drug release, and bioactive functionalities. Additionally, their application in precision medicine, particularly for cancer therapy, antimicrobial treatments, and tissue engineering, is critically examined. Challenges related to scalability, biocompatibility, and regulatory compliance are also discussed, alongside future perspectives on advancing these bioaerogels toward clinical translation. By integrating interdisciplinary insights, this review underscores the transformative potential of multimodal nanostructured bioaerogels in the next generation of intelligent drug delivery systems. Full article
(This article belongs to the Special Issue Polymers for Drug/Gene Delivery and Controlled Release)
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29 pages, 2139 KB  
Review
Overcoming Oral Cavity Barriers for Peptide Delivery Using Advanced Pharmaceutical Techniques and Nano-Formulation Platforms
by Ali A. Amer, Lewis Bingle, Amal Ali Elkordy and Cheng Shu Chaw
Biomedicines 2025, 13(11), 2735; https://doi.org/10.3390/biomedicines13112735 - 8 Nov 2025
Viewed by 655
Abstract
Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by [...] Read more.
Therapeutic peptides have gained significant attention due to their high specificity, potency, and safety profiles in treating various diseases. However, their clinical application via the oral route remains challenging. Peptides are inherently unstable in the gastrointestinal environment, where they are rapidly degraded by proteolytic enzymes and acidic pH, leading to poor bioavailability. Additionally, their large molecular size and hydrophilicity restrict passive diffusion across the epithelial barriers of the gastrointestinal tract. These limitations have traditionally necessitated parenteral administration, which reduces patient compliance and convenience. The oral cavity, comprising the buccal and sublingual mucosa, offers a promising alternative for peptide delivery. Its rich vascularization allows for rapid systemic absorption while bypassing hepatic first-pass metabolism. Furthermore, the mucosal surface provides a relatively permeable and accessible site for drug administration. However, the oral cavities also present significant barriers: the mucosal epithelium limits permeability, the presence of saliva causes rapid clearance, and enzymes in saliva contribute to peptide degradation. Therefore, innovative strategies are essential to enhance peptide stability, retention, and permeation in this environment. Nanoparticle-based delivery systems, including lipid-based carriers such as liposomes and niosomes, as well as polymeric nanoparticles like chitosan and PLGA, offer promising solutions. These nanocarriers protect peptides from enzymatic degradation, enhance mucoadhesion to prolong residence time, and facilitate controlled release. Their size and surface properties can be engineered to improve mucosal penetration, including through receptor-mediated endocytosis or by transiently opening tight junctions. Among these, niosomes have shown high encapsulation efficiency and sustained release potential, making them particularly suitable for oral peptide delivery. Despite advances, challenges remain in translating these technologies clinically, including ensuring biocompatibility, scalable manufacturing, and patient acceptance. Nevertheless, the oral cavity’s accessibility, combined with nanotechnological innovations, offers a compelling platform for personalized, non-invasive peptide therapies that could significantly improve treatment outcomes and patient quality of life. Full article
(This article belongs to the Special Issue Advances Research on Nanomedicine)
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24 pages, 7414 KB  
Article
Supramolecular Lipid Nanoparticles Based on Amine β-CD Host–Guest Lipids: Design, Mechanisms, and Biosafety
by Pin Lv, Yamin Li, Gang Du, Jiawei Ding, Jiawei Zhou, Yuan Zhang, Huang Lin, Ming Yang, Chao Zhou and Bo Yang
Pharmaceutics 2025, 17(11), 1410; https://doi.org/10.3390/pharmaceutics17111410 - 30 Oct 2025
Viewed by 492
Abstract
Background/Objectives: Lipid nanoparticles (LNPs) have demonstrated notable clinical success as advanced drug delivery systems. However, the development of novel covalently bonded ionizable lipids faces substantial technical challenges, as their modification is difficult and they have a high molecular weight. To address this issue, [...] Read more.
Background/Objectives: Lipid nanoparticles (LNPs) have demonstrated notable clinical success as advanced drug delivery systems. However, the development of novel covalently bonded ionizable lipids faces substantial technical challenges, as their modification is difficult and they have a high molecular weight. To address this issue, we report the use of host–guest complexes in supramolecular chemistry as functional lipid motifs for constructing LNPs. Methods: Ionizable amine β-cyclodextrin (amine β-CD)-derived host–guest amphiphilic lipid molecules (HGLs) were designed for the construction of multi-stage assembly supramolecular LNPs (MSLNPs). The structure–function relationships and stability of MSLNPs were explored by screening eight types of amine β-CDs and varying the ratio of HGL to yolk phosphatidylcholine. Stability screening and molecular dynamics simulations were performed to clarify the self-assembly mechanisms and optimal formulations, followed by a systematic evaluation of delivery performance. Results: MSLNPs showed a high drug-loading efficiency (> 30%), a rapid-response release in acidic environments, and multi-pathway cellular uptake. In vivo delivery experiments using ethylenediamine β-CD-based MSLNPs in mice revealed no significant immunogenicity, no significant abnormalities in organs/tissues or their functions, a unique biodistribution pattern, and pronounced renal targeting. The successful development of MSLNPs with acidic pH-responsive control, a high delivery efficiency, and renal-targeting properties simplifies LNP preparation. Conclusions: This study offers novel insights into the design of simplified LNPs and the optimization of targeted delivery, with potential applications in renal disease therapy. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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45 pages, 2725 KB  
Review
Injectable Hydrogel Systems for Targeted Drug Delivery: From Site-Specific Application to Design Strategy
by Yeji Lee, Minji Kim, Nurihan Kim, Seonyeong Byun, Soonmin Seo and Jung Y. Han
Appl. Sci. 2025, 15(21), 11599; https://doi.org/10.3390/app152111599 - 30 Oct 2025
Viewed by 693
Abstract
Injectable hydrogels are adaptable drug delivery systems capable of forming localized depots that align with the anatomical and physiological constraints of administration sites. Their performance depends on both the injection environment and the properties of the therapeutic cargo. Applications span ocular, intra-articular, subcutaneous, [...] Read more.
Injectable hydrogels are adaptable drug delivery systems capable of forming localized depots that align with the anatomical and physiological constraints of administration sites. Their performance depends on both the injection environment and the properties of the therapeutic cargo. Applications span ocular, intra-articular, subcutaneous, intramuscular, tumoral, central nervous system, and mucosal delivery, where hydrogels address challenges of clearance, retention, and compatibility. Beyond bulk depots, particulate hydrogel formats such as microgels and nanogels improve syringeability, modularity, and integration with nanoparticle carriers. Functional versatility arises from stimuli responsiveness, including pH, enzymatic, thermal, redox, and light triggers, and from hybrid designs that integrate multiple cues for precision control. Loading strategies range from passive encapsulation to affinity binding and covalent conjugation, with release governed by diffusion, degradation, and stimuli-modulated kinetics. Translational progress depends on reproducible fabrication, scalable manufacturing, and device integration, while site-dependent constraints and regulatory hurdles remain significant challenges. Full article
(This article belongs to the Special Issue Anticancer Drugs: New Developments and Discoveries)
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14 pages, 2612 KB  
Article
Extracorporal Ovary Bioreactor System with Oxygen Supply and Drug Delivery Option
by Karin Bundschu, Sabine Eberhart, Florian Maiss, Isabella Milic and Martin Hessling
Bioengineering 2025, 12(11), 1158; https://doi.org/10.3390/bioengineering12111158 - 26 Oct 2025
Viewed by 514
Abstract
Young women who have survived cancer may have lost their fertility due to cytotoxic treatments like chemotherapy or irradiation. So far, oocyte or ovarian tissue cryopreservation are well-known and well-used opportunities for fertility preservation prior cytotoxic therapies. However, these methods are not possible [...] Read more.
Young women who have survived cancer may have lost their fertility due to cytotoxic treatments like chemotherapy or irradiation. So far, oocyte or ovarian tissue cryopreservation are well-known and well-used opportunities for fertility preservation prior cytotoxic therapies. However, these methods are not possible in certain cases, like those with a high risk of ovarian metastasis or prepubertal girls. Therefore, new medical and biotechnological options are also being sought to help this patient group to fulfill their desire to have their own biological children. The investigation described here focuses on the possibility of in vitro follicle maturing. To this point, a long-term temperature and pH-controlled bioreactor system is developed that can supply a whole ovary with oxygen and nutrients over several days and offers the possibility of hormone administration or the delivery of other drugs. This bioreactor was then tested with mature bovine ovaries. After appropriate cannulation, antithrombotic vascular perfusion, and antibiotic pretreatment, the ovaries were cultured for up to 9 days without any contamination or suffering major vital cell damage. The controlled application of oocyte stimulation hormones (human menopausal gonadotropin; hMG) also enabled successful in vitro follicle growth and maturation. From a technical point of view, there is still optimization potential for this bioreactor system, but in principle, it has been demonstrated that long-term ovary cultivation and in vitro maturation of follicles are possible, which opens up further potential for these and other applications. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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30 pages, 3150 KB  
Article
Zinc-Modified Mordenite Zeolite as a Molecular Carrier for Donepezil: A Framework for Drug Delivery Applications
by Diana Guaya, Lupe Carolina Espinoza, Ximena Jaramillo-Fierro, Dagmar Gualotuña Campoverde, Lilian Sosa and Ana Cristina Calpena
Molecules 2025, 30(21), 4174; https://doi.org/10.3390/molecules30214174 - 24 Oct 2025
Viewed by 531
Abstract
The development of advanced drug delivery systems is essential for improving therapeutic efficacy, particularly in the treatment of neurodegenerative disorders such as Alzheimer’s disease. This study investigates zinc-modified mordenite zeolite (MR-ZN) as a novel platform for the controlled delivery of donepezil (DPZ), a [...] Read more.
The development of advanced drug delivery systems is essential for improving therapeutic efficacy, particularly in the treatment of neurodegenerative disorders such as Alzheimer’s disease. This study investigates zinc-modified mordenite zeolite (MR-ZN) as a novel platform for the controlled delivery of donepezil (DPZ), a cholinesterase inhibitor. Natural mordenite was modified with zinc, enhancing its surface area from 62.1 to 85.4 m2/g and improving its adsorption properties. Donepezil was successfully loaded at two doses (10 mg and 23 mg), achieving high loading efficiencies of 95% and 94%, respectively. Adsorption kinetics followed a pseudo-second-order model (R2 > 0.99), indicating that chemisorption predominates through coordination between DPZ functional groups and Zn2+ sites, while complementary physisorption via hydrogen bonding and van der Waals interactions also contributes to molecular stabilization within the zeolite framework. In vitro release studies under simulated gastrointestinal conditions demonstrated sustained and pH-responsive release profile with 80% and 82% of donepezil released after 24 h for 10 mg and 23 mg formulations, respectively. Density Functional Theory (DFT) calculations revealed favorable adsorption energy (−26.4 kJ/mol), while Bader and Electron Localization Function (ELF) analyses confirmed hydrogen bonding and electrostatic interactions without compromising the zeolite framework. These findings validate MR-ZN as structurally stable, efficient, cost-effective and biocompatible matrix for oral drug delivery. The combination of experimental data and theoretical modeling supports its potential to improve bioavailability and therapeutic performance in neurodegenerative treatment. Full article
(This article belongs to the Special Issue Design, Synthesis, and Application of Zeolite Materials)
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22 pages, 1281 KB  
Article
Preparation and Characterization of New pH-Sensitive Polyurethane Hydrogels as Anti-Cancer Drug Delivery Systems for 5-Fluorouracyl and Fluorodeoxyuridine
by Marcin Sobczak, Adam Kasiński, Karolina Kędra, Joachim Frankowski, Matylda Kurzątkowska, Karolina Watrakiewicz, Karolina Mulas, Katarzyna Strzelecka, Marcin Chodkowski, Małgorzata Krzyżowska, Andrzej Deptała and Ewa Oledzka
Int. J. Mol. Sci. 2025, 26(21), 10258; https://doi.org/10.3390/ijms262110258 - 22 Oct 2025
Viewed by 349
Abstract
In this study, non-toxic, biodegradable, and pH-sensitive polyurethane hydrogels (PUs) were prepared by using hexamethylene diisocyanate (HDI), copolymers of є-caprolactone (CL), rac-lactide (LA), and poly(ethylene glycol) (PEG), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-bPPO-b-PEO), 1,4-butanediol (BD), and L-glutamine (Gln). The [...] Read more.
In this study, non-toxic, biodegradable, and pH-sensitive polyurethane hydrogels (PUs) were prepared by using hexamethylene diisocyanate (HDI), copolymers of є-caprolactone (CL), rac-lactide (LA), and poly(ethylene glycol) (PEG), poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEO-bPPO-b-PEO), 1,4-butanediol (BD), and L-glutamine (Gln). The CL, LA, and PEG copolymers were obtained in the presence of a new synthesized catalytic system: diethylzinc/ethyl-3,4-dihydroxybenzoate. Obtained PUs were screened for their cytotoxicity, evaluated for their swelling behavior and hydrolytic degradation, and employed as hydrogel pH-responsive anti-cancer drug delivery systems (DDSs). The novel and promising hydrogel DDSs, capable of releasing 5-fluorouracyl (5-FU) and fluorodeoxyuridine (5-fluoro-2′-deoxyuridine, FUdR) in a sustained and controlled manner, were prepared and were nontoxic. Most prepared hydrogel DDSs were found to release anti-cancer drugs with first-order or zero-order kinetics. The drug release mechanism was generally denoted as Fickian or non-Fickian transport. The possibility of controlling the kinetics of drug release by changing the pH of the environment was also observed. The findings indicate that these PU hydrogels are suitable for use as intelligent DDSs for the targeted delivery of 5-FU or FUdR. We expect that the hydrogel DDSs developed will be utilized in the treatment of pancreatic cancer. Full article
(This article belongs to the Special Issue Rational Design and Application of Functional Hydrogels)
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24 pages, 4277 KB  
Article
Effect of Gellan Gum on the Properties of Collagen-HPMC Freeze-Dried Hydrogels for Mucosal Administration
by Ioana Luca, Mădălina Georgiana Albu Kaya, Raluca Țuțuianu, Cristina Elena Dinu-Pîrvu, Maria Minodora Marin, Lăcrămioara Popa, Irina Titorencu, Valentina Anuța and Mihaela Violeta Ghica
Gels 2025, 11(10), 793; https://doi.org/10.3390/gels11100793 - 2 Oct 2025
Viewed by 583
Abstract
Mucosal drug delivery is gaining attention for its ability to provide localized treatment with reduced systemic side effects. The vaginal route has been proven effective for managing gynecological conditions, though it poses certain limitations. Biopolymers can help overcome these challenges by enhancing therapeutic [...] Read more.
Mucosal drug delivery is gaining attention for its ability to provide localized treatment with reduced systemic side effects. The vaginal route has been proven effective for managing gynecological conditions, though it poses certain limitations. Biopolymers can help overcome these challenges by enhancing therapeutic efficiency and offering beneficial properties. This study aimed to develop and evaluate hydrogels and their freeze-dried forms (wafers) based on collagen, hydroxypropyl methylcellulose, and gellan gum. Initially, a collagen gel was obtained by extraction from calfskin, which was brought to a concentration of 1% and a physiological pH with 1 M sodium hydroxide solution. This gel was combined with either 2% hydroxypropyl methylcellulose gel, 1.2% gellan gum gel, or both, in different proportions. Thus, five mixed hydrogels were obtained, which, along with the three individual gels (controls), were lyophilized to obtain wafers. Furthermore, the hydrogels were assessed for rheological behavior, while the collagen structural integrity in the presence of the other biopolymers was evaluated using circular dichroism and FT-IR spectroscopy. The wafers were characterized for morphology, wettability, swelling capacity, enzymatic degradation resistance, and in vitro biocompatibility. All hydrogels exhibited non-Newtonian, pseudoplastic behavior and showed collagen structure preservation. The wafers’ characterization showed that gellan gum enhanced the hydrophilicity and enzymatic stability of the samples. In addition, the extracts from the tested samples maintained cell viability and did not affect actin cytoskeleton morphology, indicating a lack of cytotoxic effects. This study emphasizes the importance of evaluating both the physicochemical properties and biocompatibility of biopolymeric supports as a key preliminary step in the development of vaginal drug delivery platforms with biomedical applications in the management of gynecological conditions. Full article
(This article belongs to the Special Issue Advances in Functional Hydrogels and Their Applications)
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20 pages, 6572 KB  
Article
pH and Magnetic-Responsive Carboxymethyl Chitosan/Sodium Alginate Composites for Gallic Acid Delivery
by Kun Fang, Pei Li, Hanbing Wang, Xiangrui Huang and Yihan Li
Magnetochemistry 2025, 11(10), 85; https://doi.org/10.3390/magnetochemistry11100085 - 28 Sep 2025
Viewed by 637
Abstract
Gallic acid (GA) exhibits a broad range of biological activities; however, its clinical application is significantly limited by poor stability, rapid degradation, and low bioavailability. Consequently, developing responsive delivery platforms to enhance GA stability and targeted release has become an important research focus. [...] Read more.
Gallic acid (GA) exhibits a broad range of biological activities; however, its clinical application is significantly limited by poor stability, rapid degradation, and low bioavailability. Consequently, developing responsive delivery platforms to enhance GA stability and targeted release has become an important research focus. Herein, GA was encapsulated within novel composite hydrogel beads (CMC-SA-Fe3O4@GA) prepared via crosslinking carboxymethyl chitosan (CMC) and sodium alginate (SA) with Fe3O4 nanoparticles (NPs) to facilitate efficient drug delivery. The formulation was characterized and evaluated in terms of drug-loading capacity, controlled-release properties, antioxidant activity, antibacterial performance, and biocompatibility. The results indicated that the GA loading efficiency reached 31.07 ± 1.23%. Application of an external magnetic field accelerated GA release, with the observed release kinetics fitting the Ritger–Peppas model. Furthermore, antioxidant capacity, evaluated by DPPH assays, demonstrated excellent antioxidant activity of the CMC-SA-Fe3O4@GA composite beads. Antibacterial tests confirmed sustained inhibitory effects against Escherichia coli and Staphylococcus aureus. In vitro, cellular assays indicated favorable biocompatibility with normal hepatic cells (HL-7702) and effective inhibition of hepatocellular carcinoma cells (HepG2). Overall, the novel pH- and magnetic field-responsive CMC-SA-Fe3O4@GA hydrogel system developed in this work offers considerable potential for controlled delivery of phenolic compounds, demonstrating promising applicability in biomedical and food-related fields. Full article
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27 pages, 4484 KB  
Article
Formulation of Self-Emulsifying Microemulsion for Acemetacin Using D-Optimal Design: Enteric-Coated Capsule for Targeted Intestinal Release and Bioavailability Enhancement
by Zaineb Z. Abduljaleel and Khalid K. Al-Kinani
Pharmaceutics 2025, 17(10), 1270; https://doi.org/10.3390/pharmaceutics17101270 - 27 Sep 2025
Viewed by 928
Abstract
Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was [...] Read more.
Objectives: The current work aimed to formulate and optimize a self-emulsifying microemulsion drug delivery system (SEME) for acemetacin (ACM) to increase ACM’s aqueous solubility, improve oral bioavailability, and reduce gastrointestinal complications. Methods: Screening of components capable of enhancing ACM solubility was performed. Pseudo-ternary phase diagrams were performed to choose the optimal formulation ratio. The ACM-SEME formulation’s composition was optimized using D-optimal design. Oil, Smix, and water percentages were used as independent variables, while globule size, polydispersity index, ACM content, and in vitro ACM release after 90 min were used as dependent variables. Also, thermodynamic stability and transmittance percentage tests were studied. Zeta potential was assessed for the optimized ACM-SEME formulation, which was then subjected to spray drying. The dried ACM-SEME was characterized using field-emission scanning electron microscope, Fourier-transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The dried ACM-SEME formulation was filled into hard gelatin capsules and coated with Eudragit L100 to achieve pH-dependent release. Results: The antinociceptive activity of ACM-SEME was evaluated in vivo using Eddy’s hot plate test in rats, revealing a significant prolongation of the noxious time threshold compared to control groups. Ex vivo permeation studies across rat intestinal tissue confirmed the enhanced permeation potential of the ACM-SEME. Conclusions: It was concluded that the developed ACM-SEME system demonstrated improved physicochemical properties, enhanced release behavior, and superior therapeutic performance, highlighting its potential as a safer and more effective oral delivery platform for ACM. Full article
(This article belongs to the Special Issue Advances in Emulsifying Drug Delivery Systems)
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27 pages, 1325 KB  
Systematic Review
Sustained-Release Oral Delivery of NSAIDs and Acetaminophen: Advances and Recent Formulation Strategies—A Systematic Review
by Paulina Drapińska, Katarzyna Skulmowska-Polok, Joanna Chałupka and Adam Sikora
Pharmaceutics 2025, 17(10), 1264; https://doi.org/10.3390/pharmaceutics17101264 - 26 Sep 2025
Viewed by 1580
Abstract
Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction [...] Read more.
Background: Sustained-release (SR) formulations of non-steroidal anti-inflammatory drugs (NSAIDs) aim to prolong therapeutic activity, reduce dosing frequency, and improve patient adherence. However, currently marketed SR NSAIDs exhibit persistent limitations, including incomplete control over release kinetics, high interpatient variability in bioavailability, limited reduction in gastrointestinal adverse effects, and insufficient dose flexibility for individualized therapy. In many cases, conventional excipients and release mechanisms remain predominant, leaving drug-specific physicochemical and pharmacokinetic constraints only partially addressed. These gaps highlight the need for a comprehensive synthesis of recent technological advances to guide the development of more effective, patient-centered delivery systems. Methods: A narrative literature review was conducted using Web of Science and PubMed databases to identify original research articles and comprehensive technological studies on oral SR formulations of NSAIDs and paracetamol published between January 2020 and March 2025. Inclusion criteria focused on preclinical and technological research addressing formulation design, excipient innovations, and manufacturing approaches. Results: Sixty-four studies met the inclusion criteria, encompassing polymeric matrices (31%), lipid-based carriers (18%), microspheres/hydrogel beads/interpenetrating polymer networks (30%), nanostructured systems (11%), and hybrid platforms (10%). The most common strategies involved pH-dependent release, mucoadhesive systems, and floating drug delivery, aiming to optimize release kinetics, minimize mucosal irritation, and sustain therapeutic plasma levels. Advances in manufacturing—such as hot-melt extrusion, 3D printing, electrospinning, and spray drying—enabled enhanced control of drug release profiles, improved stability, and in some cases up to 30–50% prolongation of release time or reduction in Cmax fluctuations compared with conventional formulations. Conclusions: Recent formulation strategies show substantial potential to overcome long-standing limitations of SR NSAID delivery, with expected benefits for patient compliance and quality of life through reduced dosing frequency, better tolerability, and more predictable therapeutic effects. Nevertheless, integration of in vitro performance with pharmacokinetic and clinical safety outcomes remains limited, and the translation to clinical practice is still in its early stages. This review provides a comprehensive overview of current technological trends, identifies persisting gaps, and proposes future research directions to advance SR NSAID systems toward safer, more effective, and patient-focused therapy. Full article
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20 pages, 2538 KB  
Article
Development and Evaluation of Nystatin-Loaded Novasomal Gel for the Treatment of Candida albicans Infection: In Vitro Microbiological and Skin Compatibility Study
by Muhammad Abid Mustafa, Muhammad Fahad, Maryam Mughal, Namra Rasheed, Saad S. Alqahtani and Muhammad Zahid Iqbal
Gels 2025, 11(10), 774; https://doi.org/10.3390/gels11100774 - 25 Sep 2025
Viewed by 554
Abstract
Candida infections pose a significant health threat, and conventional antifungal drugs like nystatin are limited due to poor solubility, skin permeability, and frequent dosage requirements. Nystatin effectively targets Candida species by disrupting cell membranes, but formulation issues hinder clinical use. Lipid-based vesicular carriers, [...] Read more.
Candida infections pose a significant health threat, and conventional antifungal drugs like nystatin are limited due to poor solubility, skin permeability, and frequent dosage requirements. Nystatin effectively targets Candida species by disrupting cell membranes, but formulation issues hinder clinical use. Lipid-based vesicular carriers, or novasomes, provide controlled, prolonged drug release and enhanced skin penetration. This study focuses on developing nystatin-loaded novasomal gels as an advanced drug delivery system to enhance therapeutic efficacy, bioavailability, and patient compliance. The formulation was prepared using a modified ethanol injection technique, combining stearic acid, oleic acid, Span 60, cholesterol, and Carbopol to produce a stable transdermal gel. Comprehensive in vitro characterization using FTIR, SEM, XRD, and thermal analysis confirmed the chemical compatibility, morphological uniformity, and physical stability of the nystatin-loaded novasomal gel. Entrapment efficiency differed significantly among the formulations (p < 0.05), with F7 achieving the highest value (80%). All formulations maintained pH levels within the skin-friendly range of 5.5 to 7.0. Viscosity measurements, ranging from 3900 ± 110 to 4510 ± 105 cP, confirmed their appropriate consistency for dermal use. Rheological analysis showed a dominant elastic response, as indicated by storage modulus values consistently higher than the loss modulus. Particle size ranged from 4143 to 9570 nm, while PDI values remained below 0.3, reflecting uniform particle distribution. Zeta potential values were strongly negative, supporting physical stability. XRD studies indicated reduced crystallinity of nystatin within the formulations, while FTIR confirmed drug-excipient compatibility. SEM images showed spherical particles within the micrometer range. In vitro release studies demonstrated sustained drug release over 12 h, with F6 releasing the highest amount. The novasomal gel formulations-maintained stability for 30 days, with no notable alterations in pH, viscosity, or entrapment efficiency. Antifungal evaluation showed a larger inhibition zone (23 ± 2 mm) compared with the plain drug solution (15 ± 1.6 mm), while the MIC value was reduced (4.57 µg/mL), indicating greater potency. Skin irritation assessment in rats revealed only minor, temporary erythema, and the calculated Primary Irritation Index (0.22) confirmed a non-irritant profile. These findings suggest that the developed novasomal gel offers a promising approach for enhancing the treatment of fungal infections by enabling prolonged drug release, minimizing dosing frequency, and improving patient compliance. Full article
(This article belongs to the Special Issue Antimicrobial Gels and Related Process Technologies)
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13 pages, 6397 KB  
Article
The Influence of Pressure on Magnetite–Zinc Oxide Synthesis in Hydrothermal Conditions
by Miruna-Adriana Ioța, Laura-Mădălina Cursaru, Ioan Albert Tudor, Marian-Nicolae Costea, Alexandru Cristian Matei, Dumitru Valentin Dragut, Roxana Mioara Piticescu and Adriana-Gabriela Șchiopu
Crystals 2025, 15(9), 829; https://doi.org/10.3390/cryst15090829 - 22 Sep 2025
Viewed by 570
Abstract
The combination of ZnO and Fe3O4 nanoparticles represents a synergistic strategy for the treatment of skin cancer, exploiting both oxidative stress-induced cytotoxicity and hyperthermic effects for improved anticancer activity. These nanoparticles also function as drug carriers, facilitating targeted delivery and [...] Read more.
The combination of ZnO and Fe3O4 nanoparticles represents a synergistic strategy for the treatment of skin cancer, exploiting both oxidative stress-induced cytotoxicity and hyperthermic effects for improved anticancer activity. These nanoparticles also function as drug carriers, facilitating targeted delivery and reducing systemic toxicity. Furthermore, controlled-release systems activated by external stimuli, such as light, pH, temperature, or magnetic fields, optimize the accumulation of the drug in tumor tissues. In the present study, Fe3O4-ZnO composite powders were synthesized in aqueous solution through the hydrothermal method under high pressure and temperature. All synthesized powders were characterized by physicochemical and morpho-structural methods such as: FT-IR, XRD, SEM, DLS, and BET. The influence of the hydrothermal synthesis parameters (pressure and time) on the morpho-structural properties of the magnetite–zinc oxide nanocomposites was studied. Full article
(This article belongs to the Section Inorganic Crystalline Materials)
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21 pages, 5926 KB  
Article
Concave-Octahedral Fe2+-Rich Fe-MOF/FU Nano-Blocks with Enhanced pH-Responsive Nanozyme Activity Toward Stimuli-Responsive Gels for Chemo-Chemodynamic Synergistic Therapy
by Desheng Wang, Changjin Xu, Laibing Wang, Herima Qi, Riqing Cheng, Liang Bao, Huiqing Guo and Shikui Wu
Gels 2025, 11(9), 750; https://doi.org/10.3390/gels11090750 - 17 Sep 2025
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Abstract
Hydroxyl radicals (·OH) offer exceptional potential for cancer treatment through reactive oxygen species (ROS) amplification and apoptotic induction. However, conventional Fe-based metal–organic framework (Fe-MOF) nanomaterials are limited by inadequate Fe2+ concentrations, resulting in suboptimal Fenton catalytic performance. This study presents concave octahedral [...] Read more.
Hydroxyl radicals (·OH) offer exceptional potential for cancer treatment through reactive oxygen species (ROS) amplification and apoptotic induction. However, conventional Fe-based metal–organic framework (Fe-MOF) nanomaterials are limited by inadequate Fe2+ concentrations, resulting in suboptimal Fenton catalytic performance. This study presents concave octahedral Fe-MOF nanomaterials with integrated bimetallic Fe/Zn centers through controlled solvothermal synthesis. The nanoplatform exhibits high specific surface area (559 m2/g) and 5-fluorouracil (5-FU) loading efficiency (58.7%). These structural properties establish it as a potential nanobuilding block for constructing stimuli-responsive gels. With optimized Fe2+ content (57.3%), the Fe-MOF material shows enhanced nanozyme-like activity (Vmax = 4.58 × 10−7 M/s, Kcat = 1.83 × 10−3 s−1) for H2O2-mediated ·OH generation. The Fe-MOF@FU demonstrates pH-responsive drug release (76.5% at pH 5.0) and glutathione (GSH) depletion, synergistically enhancing oxidative stress. Biocompatibility studies confirm safety, while in vitro investigations show remarkable anticancer activity against 4T1 cells with 17.8% viability, supporting its dual role as an independent therapeutic agent and a functional component for future gel-based delivery systems. Full article
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