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Pharmaceutics
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Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications
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Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (20 January 2026) | Viewed by 13744

Special Issue Editor

Dr. Milena A. Vega

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Guest Editor
Departamento de Ingeniería Química y Textil, Universidad de Salamanca, Pl/La Merced s/n, 37008 Salamanca, Spain
Interests: nanomedicine; nanotechnology; nanomaterials; targeted drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are pleased to announce the publication of a Special Issue titled “Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications”, which is dedicated to exploring the latest advances in the design and application of smart materials within the pharmaceutical industry.

The objective of this Special Issue is to bring together cutting-edge research that demonstrates how responsive materials, such as hydrogels, functionalized nanoparticles, and polymeric systems, are revolutionizing drug delivery by enabling controlled, targeted, and personalized drug release. These advancements allow researchers to propose innovative strategies that enhance therapeutic efficacy, minimize side effects, and better tailor treatments to clinical needs.

We invite researchers to submit their work on materials that are sensitive to pH, temperature, and other biological stimuli, as well as practical applications in cancer treatment, inflammatory diseases, vaccine delivery, and other relevant areas.

Dr. Milena A. Vega
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • smart materials
  • drug delivery systems
  • pharmaceutical applications
  • responsive materials
  • hydrogels
  • functionalized nanoparticles
  • targeted drug release
  • biological stimuli

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Related Special Issue

Published Papers (9 papers)

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Research

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28 pages, 18564 KB  
Article
An Injectable Thermosensitive Chitosan/Astaxanthin/Ibuprofen Hydrogel Mitigates High-Voltage, Low-Current Electrical Burn Injury Through Inhibition of ROS–NF-κB Signaling-Mediated Inflammation
by Xiao Yang, Hui Wang, Wenjuan Zhang, Peng Gao, Xudong Yu, Weijia Qing, Ping Deng, Jingdian Li, Yan Luo, Li Tian, Jia Xie, Mengyan Chen, Zhengping Yu, Huifeng Pi, Ting Liu and Shenglin Luo
Pharmaceutics 2026, 18(3), 323; https://doi.org/10.3390/pharmaceutics18030323 - 3 Mar 2026
Viewed by 929
Abstract
Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive [...] Read more.
Background/Objectives: High-voltage, low-current electric shocks inflict superficial second-degree burns on the skin, accompanied by a vicious cycle of excessive oxidative stress and inflammation. As efficient treatment of such electrical burns remains a clinical challenge, we explored the efficacy of an injectable thermosensitive chitosan hydrogel engineered with an antioxidant agent (astaxanthin) and an anti-inflammatory agent (ibuprofen) for the treatment of high-voltage, low-current electrical burn injuries. Methods: The proposed CS/AST/IBU hydrogel was prepared and its thermosensitivity was characterized. Subsequently, the hydrogel was injected into the wounds of male Sprague–Dawley (SD) rats subjected to electrical burn injury (20 kV, 3 mA). Finally, a series of experiments were performed to elucidate the dynamics of wound healing and the mechanisms by which the hydrogel promotes wound repair. Results: The injectable hydrogel, through its thermally responsive gelation effect at 37 °C, adapts to the complex irregularities of the wound surface. This facilitates the release of astaxanthin and ibuprofen throughout the wound, which collectively diminish the formation of reactive oxygen species and MDA. Furthermore, it enhances the synthesis of endogenous antioxidants such as SOD, CAT, and GSH; encourages collagen deposition; stimulates the development of dermal appendages; and fosters neovascularization. It interrupts the deleterious cycle of oxidative stress and inflammation mediated by the NF-κB signaling pathway, thereby suppressing the expression of pro-inflammatory markers such as TNF-α, CD11b, and IL-1β while upregulating CD163, an anti-inflammatory receptor. Conclusions: The use of this multipronged, contour-adaptive hydrogel represents an effective strategy for complex wound management and demonstrates broad therapeutic potential for superficial second-degree electrical burns caused by high-voltage, low-current discharge. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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16 pages, 2571 KB  
Article
A Nanoparticle-Based Strategy to Stabilize 5-Azacytidine and Preserve DNA Demethylation Activity in Human Cardiac Fibroblasts
by Kantaporn Kheawfu, Chuda Chittasupho, Sudarshan Singh, Siriporn Okonogi and Narainrit Karuna
Pharmaceutics 2026, 18(1), 88; https://doi.org/10.3390/pharmaceutics18010088 - 9 Jan 2026
Viewed by 1080
Abstract
Background: 5-Azacytidine (5-Aza) is a clinically important DNMT inhibitor with the potential to modulate cardiac remodeling by epigenetically reprogramming human cardiac fibroblasts (HCFs). However, its clinical utility is limited by rapid hydrolytic degradation. Nanoparticle (NP) encapsulation offers a strategy to mitigate this instability. [...] Read more.
Background: 5-Azacytidine (5-Aza) is a clinically important DNMT inhibitor with the potential to modulate cardiac remodeling by epigenetically reprogramming human cardiac fibroblasts (HCFs). However, its clinical utility is limited by rapid hydrolytic degradation. Nanoparticle (NP) encapsulation offers a strategy to mitigate this instability. This study evaluated the physical and chemical stability of free 5-Aza and 5-Aza-loaded lipid nanoparticles (5-Aza-NP) under different storage temperatures and examined their effects on DNA methylation-related gene expression in HCFs. Methods: Hyaluronic acid-stabilized lipid NPs were prepared using a solvent displacement method. Particle size, polydispersity index (PDI), and zeta potential were monitored over four days at −20 °C, 4 °C, and 30 °C. Chemical stability was assessed using HPLC and first-order kinetic modeling. Functional activity was evaluated by treating HCFs with free 5-Aza or 5-Aza-NP stored for 96 h and measuring DNMT1, DNMT3A, and DNMT3B expression by RT-qPCR. Results: 5-Aza-NP remained physically stable at 4 °C, while −20 °C induced aggregation and 30 °C caused thermal variability. Free 5-Aza degraded rapidly at 30 °C (6.56% remaining at 72 h), whereas 5-Aza-NP preserved 11.54%. Kinetic modeling confirmed first-order degradation, with consistently longer half-lives for the NP formulation. Functionally, 5-Aza–NP preserved its ability to suppress DNMT1 expression following 96 h of storage at 4 °C, whereas free 5-Aza showed reduced activity. In contrast, DNMT3A and DNMT3B levels remained low and unchanged across all treatments. Conclusions: NP encapsulation enhances the physicochemical stability of 5-Aza and preserves its DNMT1-inhibitory activity, while DNMT3A/B remain unaffected. These findings support NP-based delivery as a promising strategy to stabilize labile epigenetic drugs such as 5-Aza. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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22 pages, 3956 KB  
Article
Aptamer-Modified Magnetic Nanoparticles as Targeted Drug Delivery Systems for Hepatocellular Carcinoma
by Alexandra Pusta, Mihaela Tertis, Bianca Ciocan, Rodica Turcu, Izabell Crăciunescu, Victor C. Diculescu, George E. Stan, Stefan Bulat, Alina Porfire, Andreea-Elena Petru, Ionel Fizeșan, Simona Mirel and Cecilia Cristea
Pharmaceutics 2025, 17(10), 1292; https://doi.org/10.3390/pharmaceutics17101292 - 2 Oct 2025
Cited by 4 | Viewed by 1575
Abstract
Background: Hepatocellular carcinoma is associated with high mortality and increasing incidence. Sorafenib, a cornerstone of therapy for advanced hepatocellular carcinoma, presents certain disadvantages, including low bioavailability and poor water solubility. This work describes a new strategy for sorafenib-targeted delivery aimed at improving [...] Read more.
Background: Hepatocellular carcinoma is associated with high mortality and increasing incidence. Sorafenib, a cornerstone of therapy for advanced hepatocellular carcinoma, presents certain disadvantages, including low bioavailability and poor water solubility. This work describes a new strategy for sorafenib-targeted delivery aimed at improving treatment efficiency and reducing side effects. Methods: Magnetic nanoparticles coated with azelaic acid were modified with aptamer molecules that specifically recognize human liver cancer cell line HepG2, ensuring specificity for the tumor tissue. The nanoparticles were further loaded with sorafenib. The obtained drug delivery system was extensively characterized using UV-Vis spectrophotometry, transmission electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. Results: The drug delivery system demonstrated a higher release of sorafenib at acidic pH compared to pH 7.4. The cell internalization of the bare and aptamer-modified magnetic nanoparticles was assessed in HepG2 and human normal foreskin fibroblasts BJ cell lines, demonstrating that the aptamer significantly enhances internalization in tumor cells, while having no impact on healthy cells. Conclusions: The sorafenib-modified nanoparticles exhibited excellent cytocompatibility with BJ cells across all tested concentrations, while showing cytotoxicity towards HepG2 cells at higher concentrations, confirming the selectivity of the system. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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24 pages, 2434 KB  
Article
Therapeutic Approach Based on Nanotechnology with Chitosan-Coated Zein Nanoparticles Containing Quercetin Against Resistant Klebsiella pneumoniae Clinical Isolates
by Azael Francisco Silva-Neto, Maria Anndressa Alves Agreles, Ana Alice Venancio Correia, Hanne Lazla Rafael de Queiroz Macêdo, Alane Rafaela de Carvalho Amaral, Alexsandra Maria Lima Scavuzzi, João Victor de Oliveira Alves, Ana Catarina Souza Lopes, Márcia Vanusa da Silva, Maria Tereza dos Santos Correia, Isabella Macário Ferro Cavalcanti and Luís André de Almeida Campos
Pharmaceutics 2025, 17(9), 1227; https://doi.org/10.3390/pharmaceutics17091227 - 22 Sep 2025
Viewed by 1533
Abstract
Background/Objectives: The study developed, characterized, and evaluated the toxicity, antibacterial and antibiofilm activity of quercetin encapsulated in chitosan-coated zein nanoparticles (QUER-ZNP-CH). Methods: QUER-ZNP-CH were prepared by the nanoprecipitation method and characterized by physicochemical analyses, stability (12 months), and release kinetics. Toxicity was evaluated [...] Read more.
Background/Objectives: The study developed, characterized, and evaluated the toxicity, antibacterial and antibiofilm activity of quercetin encapsulated in chitosan-coated zein nanoparticles (QUER-ZNP-CH). Methods: QUER-ZNP-CH were prepared by the nanoprecipitation method and characterized by physicochemical analyses, stability (12 months), and release kinetics. Toxicity was evaluated through hemocompatibility and a Tenebrio molitor larval model. Antibacterial activity (MIC/MBC, CLSI) and antibiofilm potential (crystal violet assay) were tested against resistant Klebsiella pneumoniae strains. Results: The nanoparticles were prepared, and physicochemical analyses revealed chemical interactions, efficient encapsulation of the drug, and thermal stability. The formulations remained stable over 12 months, and the release kinetics demonstrated controlled release for 72 h. No hemotoxic profile was observed and there was 95% survival of Tenebrio molitor larvae after treatment with QUER-ZNP-CH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of QUER-ZNP-CH revealed enhanced antibacterial activity of QUER, as indicated by a 32 to 64-fold reduction in the MIC and MBC values. The biofilm inhibition potential of QUER-ZNP-CH showed 60–100% inhibition and 25–95% eradication in concentrations from 0.12 to 62.5 μg/mL. Conclusions: Thus, this nanotechnology-based formulation suggests potential for the treatment of bacterial infections caused by multidrug-resistant K. pneumoniae strains. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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18 pages, 2572 KB  
Article
Stimuli-Responsive Cationic Lyotropic Liquid Crystalline Nanoparticles: Formulation Process, Physicochemical and Morphological Evaluation
by Maria Chountoulesi, Natassa Pippa, Varvara Chrysostomou, Aleksander Forys, Barbara Trzebicka, Stergios Pispas and Costas Demetzos
Pharmaceutics 2025, 17(9), 1199; https://doi.org/10.3390/pharmaceutics17091199 - 15 Sep 2025
Cited by 1 | Viewed by 1504
Abstract
Background/Objectives: Lyotropic liquid crystalline nanoparticles are promising drug delivery nanocarriers, exhibiting significant technological advantages, such as their extended internal morphology. In this study, cationic non-lamellar lyotropic–lipidic liquid crystalline nanoparticles were formulated by phytantriol lipid. Methods: The poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) block copolymer [...] Read more.
Background/Objectives: Lyotropic liquid crystalline nanoparticles are promising drug delivery nanocarriers, exhibiting significant technological advantages, such as their extended internal morphology. In this study, cationic non-lamellar lyotropic–lipidic liquid crystalline nanoparticles were formulated by phytantriol lipid. Methods: The poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) block copolymer carrying tri-phenyl-phosphine cations (TPP-QPDMAEMA-b-PLMA), was employed as a stabilizer co-assisted by other polymeric guests. The exact qualitative and quantitative formulation of the systems was investigated. Their physicochemical profile was depicted from a variety of light scattering techniques, while their microenvironmental parameters were determined by fluorescence spectroscopy using adequate probe molecules. The effect of environmental conditions was monitored, confirming stimuli-responsiveness properties. Their morphology was illustrated by cryo-TEM, revealing expanded internal assemblies. Resveratrol was incorporated into the nanoparticles and the entrapment efficiency was calculated. Results: Their properties were found to be dependent on the formulation characteristics, such as the lipid used, as well as the architecture of the polymeric stabilizer, also being found to be stealth toward proteins, exhibiting stimuli responsiveness and high entrapment efficiency. Conclusions: The studied liquid crystalline nanoparticles, being stimuli-responsive, with high cationic potential, high loading capacity and showing intriguing 3D structures, are suitable for pharmaceutical applications. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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21 pages, 7194 KB  
Article
Quality by Design (QbD)-Based Development of a Self-Nanoemulsifying Drug Delivery System for the Ocular Delivery of Flurbiprofen
by Ju-Hwan Jeong, Tae-Han Yoon, Si-Won Ryu, Min-Gyeong Kim, Gu-Hae Kim, Ye-Jin Oh, Su-Jeong Lee, Na-Woon Kwak, Kyu-Ho Bang and Kyeong-Soo Kim
Pharmaceutics 2025, 17(5), 629; https://doi.org/10.3390/pharmaceutics17050629 - 9 May 2025
Cited by 4 | Viewed by 1933
Abstract
Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and [...] Read more.
Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and increased bioavailability of the drug. Methods: The levels of each factor(X) were established using a pseudo-ternary diagram, and the Box-Behnken design (BBD) was used to evaluate the components of oil (18.9 mg), surfactant (70.7 mg), and co-surfactant (10.0 mg) to optimize the SNEDDS formulation. The response(Y) considered were particle size, polydispersity index (PDI), transmittance, and stability. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to analyze the particle size and morphology. In vitro and ex vivo diffusion tests were conducted to assess drug flux and permeability. Result: Using a response optimization tool, the values of each X factor were optimized to achieve a small particle size (nm), a low polydispersity index (PDI), and high transmittance (%), resulting in a formulation prepared with 18.9 mg of oil, 70.7 mg of surfactant, and 10.0 mg of co-surfactant. The optimized SNEDDS exhibited a small particle size of 24.89 nm, a minimal PDI of 0.068, and a high transmittance of 74.85%. A transmission electron microscopy (TEM) analysis confirmed the presence of uniform spherical nanoemulsion droplets with an observed mean diameter of less than 25 nm, corroborating the dynamic light scattering (DLS) measurements. Furthermore, the SNEDDS demonstrated improved stability under the stress conditions of heating–cooling cycles, with no phase separation, creaming, or caking observed and no differences in its particle size, PDI, or transmittance. In vitro and ex vivo diffusion tests demonstrated that the flux of the optimized SNEDDS (2.723 ± 0.133 mg/cm2, 5.446 ± 0.390 μg/cm2) was about 2.5 and 4 times higher than that of the drug dispersion, and the initial diffusion was faster, which is suitable for the characteristics of eye drops. Conclusions: Therefore, the formulation of a flurbiprofen-loaded SNEDDS (FLU-SNE) was successfully optimized using the QbD approach. The optimized FLU-SNE exhibited excellent stability and enhanced permeability, suggesting its potential effectiveness in treating various ocular inflammations, including uveitis and cystoid macular edema. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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21 pages, 5352 KB  
Article
Kollicoat® Smartseal 100P for Developing Theophylline Pellets: Exploring Taste-Masking Potential for Pediatric Applications
by Neeraja Komanduri, Mashan Almutairi, Rasha M. Elkanayati, Nagireddy Dumpa, Arun Butreddy, Suresh Bandari and Michael A. Repka
Pharmaceutics 2025, 17(4), 413; https://doi.org/10.3390/pharmaceutics17040413 - 25 Mar 2025
Cited by 5 | Viewed by 2086
Abstract
Background/Objectives: This study aimed to develop and evaluate taste-masked theophylline pellets using hot-melt extrusion (HME) technology. Additionally, the study evaluates the efficacy of various taste-masking polymers by comparing three pH-dependent polymers, Kollicoat® Smartseal 100P, Eudragit® EPO, and Kollicoat® MAE 100-55, [...] Read more.
Background/Objectives: This study aimed to develop and evaluate taste-masked theophylline pellets using hot-melt extrusion (HME) technology. Additionally, the study evaluates the efficacy of various taste-masking polymers by comparing three pH-dependent polymers, Kollicoat® Smartseal 100P, Eudragit® EPO, and Kollicoat® MAE 100-55, in masking taste and optimizing drug release. Methods: Formulations were designed with varying drug loads (10%, 20%, and 30%) and plasticizer concentrations (20% and 30% PEG 1500). Lead formulations were characterized using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), bitter threshold level, and in vitro release testing. Stability was assessed under accelerated conditions (40 °C ± 2 °C and 75% ± 5% RH) for three months. Results: DSC confirmed homogenous dispersion of the drug within the polymer matrix. The optimized formulation comprising 20% theophylline, 20% PEG 1500, and 60% Kollicoat® Smartseal 100P demonstrated effective taste masking, releasing only 1.1% of the drug in simulated salivary fluid (SSF) within two minutes, significantly lower than the pure drug (29.5%, p < 0.05), Kollicoat® MAE 100-55 (2.8%, p < 0.05), and comparable to Eudragit® EPO (2.1%, p > 0.05). Solubility studies further confirmed that theophylline release from the lead formulations remained well below its reported bitter threshold, which could prevent taste perception and mitigate bitterness. In gastric fluid, complete drug release was achieved from Kollicoat® Smartseal 100P and Eudragit® EPO, while Kollicoat® MAE 100-55 exhibited limited release. Stability studies showed that the Kollicoat® Smartseal 100P formulation maintained its texture, taste-masking efficacy, and dissolution profile under accelerated conditions. Conclusions: The study demonstrates the novel exploration of Kollicoat® Smartseal 100P for HME application, and its effectiveness in achieving robust taste masking for theophylline, improving patient compliance, particularly in pediatric and geriatric populations. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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Review

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25 pages, 1509 KB  
Review
Microbiome-Responsive Hydrogels: From Biological Cues to Smart Biomaterials
by Rajesh Vadlapatla, Amir Nasrolahi Shirazi, Ajoy Koomer, Judy Weng, Matthew Ernest Ghilarducci, Alai Qudus and Keykavous Parang
Pharmaceutics 2026, 18(3), 284; https://doi.org/10.3390/pharmaceutics18030284 - 24 Feb 2026
Viewed by 1083
Abstract
Background: Stimuli-responsive hydrogels (SRHs) are smart polymeric materials that undergo reversible physicochemical changes in response to abiotic cues and externally applied fields, enabling applications in drug delivery, wound healing, and tissue engineering. However, they exhibit limited biological specificity and do not adequately reflect [...] Read more.
Background: Stimuli-responsive hydrogels (SRHs) are smart polymeric materials that undergo reversible physicochemical changes in response to abiotic cues and externally applied fields, enabling applications in drug delivery, wound healing, and tissue engineering. However, they exhibit limited biological specificity and do not adequately reflect the dynamic, disease-relevant complexity of native tissue microenvironments. Microbe-colonized tissues display distinctive biochemical features driven, shaped by microbial metabolism, including localized pH gradients, short-chain fatty acid production, secretion of quorum-sensing molecules, biofilm formation, and expression of specialized enzymes. These endogenous, spatiotemporally regulated signals are closely linked to host physiology and pathology but remain underutilized in hydrogel design. This review aims to highlight microbiome-responsive hydrogels (MRHs) as a strategy to address this gap. Methods: This study summarizes current engineering approaches, key microbial stimuli, and emerging biomedical applications of MRHs, with emphasis on translational and regulatory challenges. Results: Microbiome-responsive hydrogels (MRHs) address this gap by leveraging microbial metabolic and biochemical cues to induce swelling, degradation, drug release, antibacterial activity, or structural transformation. By directly coupling to microbe-derived stimuli, MRHs offer improved physiological relevance, enhanced local specificity, and new opportunities for precision therapy targeting disease-associated microbial niches. Conclusions: Despite their promise, MRHs remain an early and fragmented field, lacking standardized biological triggers, material design frameworks, and performance evaluation strategies. This review summarizes current engineering approaches, key microbial stimuli, and emerging biomedical applications, with emphasis on translational and regulatory challenges, positioning MRHs as an underexplored platform for next-generation smart biomaterials. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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23 pages, 1363 KB  
Review
Sialic Acid in Neurodegenerative and Psychiatric Disorders: From Molecular Regulation to Targeted Nanocarrier-Based Therapy
by Natalia Treder and Tomasz Bączek
Pharmaceutics 2025, 17(12), 1593; https://doi.org/10.3390/pharmaceutics17121593 - 10 Dec 2025
Cited by 1 | Viewed by 1023
Abstract
In recent years, the exploration of molecular and cellular mechanisms underlying central nervous system (CNS) disorders has expanded beyond classical neurotransmitter- and receptor-based approaches toward a more integrated view including immune, metabolic, and glycosylation processes. Among these, sialic acid and its derivatives have [...] Read more.
In recent years, the exploration of molecular and cellular mechanisms underlying central nervous system (CNS) disorders has expanded beyond classical neurotransmitter- and receptor-based approaches toward a more integrated view including immune, metabolic, and glycosylation processes. Among these, sialic acid and its derivatives have emerged as critical regulators of neuronal communication, immune modulation, and synaptic plasticity. Their involvement ranges from maintaining neurochemical homeostasis under physiological conditions to contributing to the onset and progression of neurodegenerative and psychiatric diseases. Given the central role of sialylation in cellular recognition, receptor signaling, and blood–brain barrier (BBB) interactions, understanding these pathways provides valuable insight for the development of advanced therapeutic and diagnostic strategies. This review highlights recent evidence linking altered sialic acid metabolism and polysialylation to Alzheimer’s disease and other neurodegenerative and psychiatric disorders. It further discusses the potential of sialic acid-related mechanisms as novel molecular targets and their integration into innovative nanocarrier-based drug delivery systems designed to improve brain penetration, selectivity, and therapeutic efficacy. Finally, current challenges and future perspectives in translating sialic acid-based approaches into clinical applications are addressed. Full article
(This article belongs to the Special Issue Smart Materials for Advanced Drug Delivery Systems and Pharmaceutical Applications)
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