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Search Results (1,754)

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Keywords = drug release profile

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26 pages, 3940 KiB  
Article
In Vitro Proof-of-Concept Study: Lidocaine and Epinephrine Co-Loaded in a Mucoadhesive Liquid Crystal Precursor System for Topical Oral Anesthesia
by Giovana Maria Fioramonti Calixto, Aylla Mesquita Pestana, Arthur Antunes Costa Bezerra, Marcela Tavares Luiz, Jonatas Lobato Duarte, Marlus Chorilli and Michelle Franz-Montan
Pharmaceuticals 2025, 18(8), 1166; https://doi.org/10.3390/ph18081166 - 6 Aug 2025
Abstract
Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and [...] Read more.
Background: Local anesthesia is essential for most dental procedures, but its parenteral administration is often painful. Topical anesthetics are commonly used to minimize local anesthesia pain; however, commercial formulations fail to fully prevent the discomfort of local anesthetic injection. Methods: We developed and characterized a novel lidocaine and epinephrine co-loaded liquid crystalline precursor system (LCPS) for topical anesthesia. The formulation was structurally characterized using polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological behavior was assessed through continuous and oscillatory rheological analyses. Texture profile analysis, in vitro mucoadhesive force evaluation, in vitro drug release and permeation studies, and an in vivo toxicity assay using the chicken chorioallantoic membrane (CAM) model were also conducted. Results: PLM and SAXS confirmed the transition of the LCPS from a microemulsion to a lamellar liquid crystalline structure upon contact with artificial saliva. This transition enhanced formulation consistency by over 100 times and tripled mucoadhesion strength. The LCPS also provided controlled drug release, reducing permeation flow by 93% compared to the commercial formulation. Importantly, the CAM assay indicated that the LCPS exhibited similar toxicity to the commercial product. Conclusions: The developed LCPS demonstrated promising physicochemical and biological properties for topical anesthesia, including enhanced mucoadhesion, controlled drug delivery, and acceptable biocompatibility. These findings support its potential for in vivo application and future clinical use to reduce pain during dental anesthesia procedures. Full article
(This article belongs to the Special Issue Advances in Topical and Mucosal Drug Delivery Systems)
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35 pages, 1115 KiB  
Review
Resveratrol as a Novel Therapeutic Approach for Diabetic Retinopathy: Molecular Mechanisms, Clinical Potential, and Future Challenges
by Snježana Kaštelan, Suzana Konjevoda, Ana Sarić, Iris Urlić, Ivana Lovrić, Samir Čanović, Tomislav Matejić and Ana Šešelja Perišin
Molecules 2025, 30(15), 3262; https://doi.org/10.3390/molecules30153262 - 4 Aug 2025
Viewed by 133
Abstract
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut [...] Read more.
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article
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32 pages, 2710 KiB  
Review
Polyphosphazene-Based Nanotherapeutics
by Sara Gutierrez-Gutierrez, Rocio Mellid-Carballal, Noemi Csaba and Marcos Garcia-Fuentes
J. Funct. Biomater. 2025, 16(8), 285; https://doi.org/10.3390/jfb16080285 - 2 Aug 2025
Viewed by 307
Abstract
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide [...] Read more.
Poly(organo)phosphazenes (PPZs) are increasingly recognized as versatile biomaterials for drug delivery applications in nanomedicine. Their unique hybrid structure—featuring an inorganic backbone and highly tunable organic side chains—confers exceptional biocompatibility and adaptability. Through precise synthetic methodologies, PPZs can be engineered to exhibit a wide spectrum of functional properties, including the formation of multifunctional nanostructures tailored for specific therapeutic needs. These attributes enable PPZs to address several critical challenges associated with conventional drug delivery systems, such as poor pharmacokinetics and pharmacodynamics. By modulating solubility profiles, enhancing drug stability, enabling targeted delivery, and supporting controlled release, PPZs offer a robust platform for improving therapeutic efficacy and patient outcomes. This review explores the fundamental chemistry, biopharmaceutical characteristics, and biomedical applications of PPZs, particularly emphasizing their role in zero-dimensional nanotherapeutic systems, including various nanoparticle formulations. PPZ-based nanotherapeutics are further examined based on their drug-loading mechanisms, which include electrostatic complexation in polyelectrolytic systems, self-assembly in amphiphilic constructs, and covalent conjugation with active pharmaceutical agents. Together, these strategies underscore the potential of PPZs as a next-generation material for advanced drug delivery platforms. Full article
(This article belongs to the Special Issue Nanomaterials for Drug Targeting and Drug Delivery (2nd Edition))
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18 pages, 1621 KiB  
Article
The Evaluation of Cellulose from Agricultural Waste as a Polymer for the Controlled Release of Ibuprofen Through the Formulation of Multilayer Tablets
by David Sango-Parco, Lizbeth Zamora-Mendoza, Yuliana Valdiviezo-Cuenca, Camilo Zamora-Ledezma, Si Amar Dahoumane, Floralba López and Frank Alexis
Bioengineering 2025, 12(8), 838; https://doi.org/10.3390/bioengineering12080838 - 1 Aug 2025
Viewed by 317
Abstract
This research demonstrates the potential of plant waste cellulose as a remarkable biomaterial for multilayer tablet formulation. Rice husks (RC) and orange peels (OC) were used as cellulose sources and characterized for a comparison with commercial cellulose. The FTIR characterization shows minimal differences [...] Read more.
This research demonstrates the potential of plant waste cellulose as a remarkable biomaterial for multilayer tablet formulation. Rice husks (RC) and orange peels (OC) were used as cellulose sources and characterized for a comparison with commercial cellulose. The FTIR characterization shows minimal differences in their chemical components, making them equivalent for compression into tablets containing ibuprofen. TGA measurements indicate that the RC is slightly better for multilayer formulations due to its favorable degradation profile. This is corroborated by an XRD analysis that reveals its higher crystalline fraction (~55%). The use of a heat press at combined high pressures and temperatures allows the layer-by-layer tablet formulation of ibuprofen, taken as a model drug. Additionally, this study compares the release profile of three types of tablets compressed with cellulose: mixed (MIX), two-layer (BL), and three-layer (TL). The MIX tablet shows a profile like that of conventional ibuprofen tablets. Although both BL and TL tablets significantly reduce their release percentage in the first hours, the TL ones have proven to be better in the long run. In fact, formulations made of extracted cellulose sandwiching ibuprofen display a zero-order release profile and prolonged release since the drug release amounts to ~70% after 120 h. This makes the TL formulations ideal for maintaining the therapeutic effect of the drug and improving patients’ wellbeing and compliance while reducing adverse effects. Full article
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24 pages, 5797 KiB  
Article
Topical Meglumine Antimoniate Gel for Cutaneous Leishmaniasis: Formulation, Evaluation, and In Silico Insights
by Lilian Sosa, Lupe Carolina Espinoza, Alba Pujol, José Correa-Basurto, David Méndez-Luna, Paulo Sarango-Granda, Diana Berenguer, Cristina Riera, Beatriz Clares-Naveros, Ana Cristina Calpena, Rafel Prohens and Marcelle Silva-Abreu
Gels 2025, 11(8), 601; https://doi.org/10.3390/gels11080601 - 1 Aug 2025
Viewed by 306
Abstract
Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal [...] Read more.
Leishmaniasis is an infectious disease common in tropical and subtropical regions worldwide. This study aimed to develop a topical meglumine antimoniate gel (MA-gel) for the treatment of cutaneous leishmaniasis. The MA-gel was characterized in terms of morphology, pH, swelling, porosity, rheology, and thermal properties by differential scanning calorimetry (DSC). Biopharmaceutical evaluation included in vitro drug release and ex vivo skin permeation. Safety was evaluated through biomechanical skin property measurements and cytotoxicity in HaCaT and RAW 267 cells. Leishmanicidal activity was tested against promastigotes and amastigotes of Leishmania infantum, and in silico studies were conducted to explore possible mechanisms of action. The composition of the MA-gel included 30% MA, 20% Pluronic® F127 (P407), and 50% water. Scanning electron microscopy revealed a sponge-like and porous internal structure of the MA-gel. This formula exhibited a pH of 5.45, swelling at approximately 12 min, and a porosity of 85.07%. The DSC showed that there was no incompatibility between MA and P407. Drug release followed a first-order kinetic profile, with 22.11 µg/g/cm2 of the drug retained in the skin and no permeation into the receptor compartment. The MA-gel showed no microbial growth, no cytotoxicity in keratinocytes, and no skin damage. The IC50 for promastigotes and amastigotes of L. infantum were 3.56 and 23.11 µg/mL, respectively. In silico studies suggested that MA could act on three potential therapeutic targets according to its binding mode. The MA-gel demonstrated promising physicochemical, safety, and antiparasitic properties, supporting its potential as a topical treatment for cutaneous leishmaniasis. Full article
(This article belongs to the Special Issue Functional Hydrogels: Design, Processing and Biomedical Applications)
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25 pages, 17212 KiB  
Article
Three-Dimensional Printing of Personalized Carbamazepine Tablets Using Hydrophilic Polymers: An Investigation of Correlation Between Dissolution Kinetics and Printing Parameters
by Lianghao Huang, Xingyue Zhang, Qichen Huang, Minqing Zhu, Tiantian Yang and Jiaxiang Zhang
Polymers 2025, 17(15), 2126; https://doi.org/10.3390/polym17152126 - 1 Aug 2025
Viewed by 383
Abstract
Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision [...] Read more.
Background: Precision medicine refers to the formulation of personalized drug regimens according to the individual characteristics of patients to achieve optimal efficacy and minimize adverse reactions. Additive manufacturing (AM), also known as three-dimensional (3D) printing, has emerged as an optimal solution for precision drug delivery, enabling customizable and the fabrication of multifunctional structures with precise control over morphology and release behavior in pharmaceutics. However, the influence of 3D printing parameters on the printed tablets, especially regarding in vitro and in vivo performance, remains poorly understood, limiting the optimization of manufacturing processes for controlled-release profiles. Objective: To establish the fabrication process of 3D-printed controlled-release tablets via comprehensively understanding the printing parameters using fused deposition modeling (FDM) combined with hot-melt extrusion (HME) technologies. HPMC-AS/HPC-EF was used as the drug delivery matrix and carbamazepine (CBZ) was used as a model drug to investigate the in vitro drug delivery performance of the printed tablets. Methodology: Thermogravimetric analysis (TGA) was employed to assess the thermal compatibility of CBZ with HPMC-AS/HPC-EF excipients up to 230 °C, surpassing typical processing temperatures (160–200 °C). The formation of stable amorphous solid dispersions (ASDs) was validated using differential scanning calorimetry (DSC), hot-stage polarized light microscopy (PLM), and powder X-ray diffraction (PXRD). A 15-group full factorial design was then used to evaluate the effects of the fan speed (20–100%), platform temperature (40–80 °C), and printing speed (20–100 mm/s) on the tablet properties. Response surface modeling (RSM) with inverse square-root transformation was applied to analyze the dissolution kinetics, specifically t50% (time for 50% drug release) and Q4h (drug released at 4 h). Results: TGA confirmed the thermal compatibility of CBZ with HPMC-AS/HPC-EF, enabling stable ASD formation validated by DSC, PLM, and PXRD. The full factorial design revealed that printing speed was the dominant parameter governing dissolution behavior, with high speeds accelerating release and low speeds prolonging release through porosity-modulated diffusion control. RSM quadratic models showed optimal fits for t50% (R2 = 0.9936) and Q4h (R2 = 0.9019), highlighting the predictability of release kinetics via process parameter tuning. This work demonstrates the adaptability of polymer composite AM for tailoring drug release profiles, balancing mechanical integrity, release kinetics, and manufacturing scalability to advance multifunctional 3D-printed drug delivery devices in pharmaceutics. Full article
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46 pages, 2561 KiB  
Review
Lipid-Based Nanotechnologies for Delivery of Green Tea Catechins: Advances, Challenges, and Therapeutic Potential
by Stanila Stoeva-Grigorova, Nadezhda Ivanova, Yoana Sotirova, Maya Radeva-Ilieva, Nadezhda Hvarchanova and Kaloyan Georgiev
Pharmaceutics 2025, 17(8), 985; https://doi.org/10.3390/pharmaceutics17080985 - 30 Jul 2025
Viewed by 196
Abstract
Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs [...] Read more.
Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs and cells that are in need. For decades, green tea catechins (GTCs) have been a case in point. Because of their low redox potential and favorable positioning of hydroxyl groups, these flavonoid representatives (namely, catechin—C, epicatechin—EC, epicatechin gallate—ECG, epigallocatechin—EGC, epigallocatechin gallate—EGCG) are among the most potent plant-derived (and not only) antioxidants. The proven anti-inflammatory, neuroprotective, antimicrobial, and anticarcinogenic properties of these phytochemicals further contribute to their favorable pharmacological profile. Doubtlessly, GTCs hold the potential to “cope” with the majority of today‘s socially significant diseases, yet their mass use in clinical practice is still limited. Several factors related to the compounds’ membrane penetrability, chemical stability, and solubility overall determine their low bioavailability. Moreover, the antioxidant-to-pro-oxidant transitioning behavior of GTCs is highly conditional and, to a certain degree, unpredictable. The nanoparticulate delivery systems represent a logical approach to overcoming one or more of these therapeutic challenges. This review particularly focuses on the lipid-based nanotechnologies known to be a leading choice when it comes to drug permeation enhancement and not drug release modification nor drug stabilization solely. It is our goal to present the privileges of encapsulating green tea catechins in either vesicular or particulate lipid carriers with respect to the increasingly popular trends of advanced phytotherapy and functional nutrition. Full article
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33 pages, 2684 KiB  
Review
Biocompatible Natural Polymer-Based Amorphous Solid Dispersion System Improving Drug Physicochemical Properties, Stability, and Efficacy
by Arif Budiman, Helen Ivana, Kelly Angeline Huang, Stella Aurelia Huang, Mazaya Salwa Nadhira, Agus Rusdin and Diah Lia Aulifa
Polymers 2025, 17(15), 2059; https://doi.org/10.3390/polym17152059 - 28 Jul 2025
Viewed by 378
Abstract
Poor aqueous solubility still disqualifies many promising drug candidates at late stages of development. Amorphous solid dispersion (ASD) technology solves this limitation by trapping the active pharmaceutical ingredient (API) in a high-energy, non-crystalline form, yet most marketed ASDs rely on synthetic carriers such [...] Read more.
Poor aqueous solubility still disqualifies many promising drug candidates at late stages of development. Amorphous solid dispersion (ASD) technology solves this limitation by trapping the active pharmaceutical ingredient (API) in a high-energy, non-crystalline form, yet most marketed ASDs rely on synthetic carriers such as polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC), which raise concerns about long-term biocompatibility, residual solvent load, and sustainability. This study summarizes the emergence of natural polymer-based ASDs (NP-ASDs), along with the bond mechanism reactions through which these natural polymers enhance drug performance. As a result, NP-ASDs exhibit improved physical stability and significantly enhance the dissolution rate of poorly soluble drugs. The structural features of natural polymers play a critical role in stabilizing the amorphous state and modulating drug release profiles. These findings support the growing potential of NP-ASDs as sustainable and biocompatible alternatives to synthetic carriers in pharmaceutical development. Full article
(This article belongs to the Section Biobased and Biodegradable Polymers)
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18 pages, 2562 KiB  
Article
Enhancing the Solubility and Oral Bioavailability of Trimethoprim Through PEG-PLGA Nanoparticles: A Comprehensive Evaluation of In Vitro and In Vivo Performance
by Yaxin Zhou, Guonian Dai, Jing Xu, Weibing Xu, Bing Li, Shulin Chen and Jiyu Zhang
Pharmaceutics 2025, 17(8), 957; https://doi.org/10.3390/pharmaceutics17080957 - 24 Jul 2025
Viewed by 283
Abstract
Background/Objectives: Trimethoprim (TMP), a sulfonamide antibacterial synergist, is widely used in antimicrobial therapy owing to its broad-spectrum activity and clinical efficacy in treating respiratory, urinary tract, and gastrointestinal infections. However, its application is limited due to poor aqueous solubility, a short elimination half-life [...] Read more.
Background/Objectives: Trimethoprim (TMP), a sulfonamide antibacterial synergist, is widely used in antimicrobial therapy owing to its broad-spectrum activity and clinical efficacy in treating respiratory, urinary tract, and gastrointestinal infections. However, its application is limited due to poor aqueous solubility, a short elimination half-life (t1/2), and low bioavailability. In this study, we proposed TMP loaded by PEG-PLGA polymer nanoparticles (NPs) to increase its efficacy. Methods: We synthesized and thoroughly characterized PEG-PLGA NPs loaded with TMP using an oil-in-water (O/W) emulsion solvent evaporation method, denoted as PEG-PLGA/TMP NPs. Drug loading capacity (LC) and encapsulation efficiency (EE) were quantified by ultra-performance liquid chromatography (UPLC). Comprehensive investigations were conducted on the stability of PEG-PLGA/TMP NPs, in vitro drug release profiles, and in vivo pharmacokinetics. Results: The optimized PEG-PLGA/TMP NPs displayed a high LC of 34.0 ± 1.6%, a particle size of 245 ± 40 nm, a polydispersity index (PDI) of 0.103 ± 0.019, a zeta potential of −23.8 ± 1.2 mV, and an EE of 88.2 ± 4.3%. The NPs remained stable at 4 °C for 30 days and under acidic conditions. In vitro release showed sustained biphasic kinetics and enhanced cumulative release, 86% at pH 6.8, aligning with first-order models. Pharmacokinetics in rats revealed a 2.82-fold bioavailability increase, prolonged half-life 2.47 ± 0.19 h versus 0.72 ± 0.08 h for free TMP, and extended MRT 3.10 ± 0.11 h versus 1.27 ± 0.11 h. Conclusions: PEG-PLGA NPs enhanced the solubility and oral bioavailability of TMP via high drug loading, stability, and sustained-release kinetics, validated by robust in vitro-in vivo correlation, offering a promising alternative for clinical antimicrobial therapy. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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21 pages, 1905 KiB  
Article
Wax-Based Sustained-Release Felodipine Oral Dosage Forms Manufactured Using Hot-Melt Extrusion and Their Resistance to Alcohol-Induced Dose Dumping
by Gerard Sweeney, Dijia Liu, Taher Hatahet, David S. Jones, Shu Li and Gavin P. Andrews
Pharmaceutics 2025, 17(8), 955; https://doi.org/10.3390/pharmaceutics17080955 - 24 Jul 2025
Viewed by 397
Abstract
Background/Objectives: Hot-melt extrusion (HME) has gained prominence for the manufacture of sustained-release oral dosage forms, yet the application of wax-based matrices and their resilience to alcohol-induced dose dumping (AIDD) remains underexplored. This study aimed to develop and characterise wax-based sustained-release felodipine formulations, with [...] Read more.
Background/Objectives: Hot-melt extrusion (HME) has gained prominence for the manufacture of sustained-release oral dosage forms, yet the application of wax-based matrices and their resilience to alcohol-induced dose dumping (AIDD) remains underexplored. This study aimed to develop and characterise wax-based sustained-release felodipine formulations, with a particular focus on excipient functionality and robustness against AIDD. Methods: Felodipine sustained-release formulations were prepared via HME using Syncrowax HGLC as a thermally processable wax matrix. Microcrystalline cellulose (MCC) and lactose monohydrate were incorporated as functional fillers and processing aids. The influence of wax content and filler type on mechanical properties, wettability, and drug release behaviour was systematically evaluated. Ethanol susceptibility testing was conducted under simulated co-ingestion conditions (4%, 20%, and 40% v/v ethanol) to assess AIDD risk. Results: MCC-containing tablets demonstrated superior sustained-release characteristics over 24 h, showing better wettability and disintegration. In contrast, tablets formulated with lactose monohydrate remained structurally intact during dissolution, overly restricting drug release. This limitation was effectively addressed through granulation, where reduced particle size significantly improved surface accessibility, with 0.5–1 mm granules achieving a satisfactory release profile. Ethanol susceptibility testing revealed divergent behaviours between the two filler systems. Unexpectedly, MCC-containing tablets showed suppressed drug release in ethanolic media, likely resulting from inhibitory effect of ethanol on filler swelling and disintegration. Conversely, formulations containing lactose monohydrate retained their release performance in up to 20% v/v ethanol, with only high concentrations (40% v/v) compromising matrix drug-retaining functionality and leading to remarkably increased drug release. Conclusions: This study highlights the pivotal role of excipient type and constitutional ratios in engineering wax-based sustained-release formulations. It further contributes to the understanding of AIDD risk through in vitro assessment and offers a rational design strategy for robust, alcohol-resistant oral delivery systems for felodipine. Full article
(This article belongs to the Special Issue Advances in Hot Melt Extrusion Technology)
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26 pages, 4405 KiB  
Review
Nanocarriers for Combination Therapy in Pancreatic Ductal Adenocarcinoma: A Comprehensive Review
by Iris Pontón and David Sánchez-García
Nanomaterials 2025, 15(15), 1139; https://doi.org/10.3390/nano15151139 - 22 Jul 2025
Viewed by 483
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers worldwide, characterized by late diagnosis, aggressive progression, and poor response to conventional monotherapies. Combination therapies have emerged as a promising approach to overcome multidrug resistance (MDR), enhance efficacy, and target the complex tumor [...] Read more.
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers worldwide, characterized by late diagnosis, aggressive progression, and poor response to conventional monotherapies. Combination therapies have emerged as a promising approach to overcome multidrug resistance (MDR), enhance efficacy, and target the complex tumor microenvironment (TME). Nanoparticle-based drug delivery systems (DDSs) have gained significant attention for their ability to co-deliver multiple agents with controlled release profiles. This review comprehensively examines nanoparticle-based platforms developed for PDAC combination therapies, focusing on small-molecule drugs. The systems discussed are drawn from studies published between 2005 and 2025. Full article
(This article belongs to the Special Issue Nanoparticles for Multiple Drug Release)
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34 pages, 6295 KiB  
Article
ROS/Enzyme Dual-Responsive Drug Delivery System for Targeted Colorectal Cancer Therapy: Synergistic Chemotherapy, Anti-Inflammatory, and Gut Microbiota Modulation
by Xin Zhang, Ruonan Lian, Bingbing Fan, Lei Meng, Pengxia Zhang, Yu Zhang and Weitong Sun
Pharmaceutics 2025, 17(7), 940; https://doi.org/10.3390/pharmaceutics17070940 - 21 Jul 2025
Viewed by 434
Abstract
Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral [...] Read more.
Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, driven by chronic inflammation, gut microbiota dysbiosis, and complex tumor microenvironment interactions. Current therapies are limited by systemic toxicity and poor tumor accumulation. This study aimed to develop a ROS/enzyme dual-responsive oral drug delivery system, KGM-CUR/PSM microspheres, to achieve precise drug release in CRC and enhance tumor-specific drug accumulation, which leverages high ROS levels in CRC and the β-mannanase overexpression in colorectal tissues. Methods: In this study, we synthesized a ROS-responsive prodrug polymer (PSM) by conjugating polyethylene glycol monomethyl ether (mPEG) and mesalazine (MSL) via a thioether bond. CUR was then encapsulated into PSM using thin-film hydration to form tumor microenvironment-responsive micelles (CUR/PSM). Subsequently, konjac glucomannan (KGM) was employed to fabricate KGM-CUR/PSM microspheres, enabling targeted delivery for colorectal cancer therapy. The ROS/enzyme dual-response properties were confirmed through in vitro drug release studies. Cytotoxicity, cellular uptake, and cell migration were assessed in SW480 cells. In vivo efficacy was evaluated in AOM/DSS-induced CRC mice, monitoring tumor growth, inflammatory markers (TNF-α, IL-1β, IL-6, MPO), and gut microbiota composition. Results: In vitro drug release studies demonstrated that KGM-CUR/PSM microspheres exhibited ROS/enzyme-responsive release profiles. CUR/PSM micelles demonstrated significant anti-CRC efficacy in cytotoxicity assays, cellular uptake studies, and cell migration assays. In AOM/DSS-induced CRC mice, KGM-CUR/PSM microspheres significantly improved survival and inhibited CRC tumor growth, and effectively reduced the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and myeloperoxidase (MPO). Histopathological and microbiological analyses revealed near-normal colon architecture and microbial diversity in the KGM-CUR/PSM group, confirming the system’s ability to disrupt the “inflammation-microbiota-tumor” axis. Conclusions: The KGM-CUR/PSM microspheres demonstrated a synergistic enhancement of anti-tumor efficacy by inducing apoptosis, alleviating inflammation, and modulating the intestinal microbiota, which offers a promising stimuli-responsive drug delivery system for future clinical treatment of CRC. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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10 pages, 2328 KiB  
Article
Vertical Hot-Melt Extrusion: The Next Challenge in Innovation
by Maël Gallas, Ghouti Medjahdi, Pascal Boulet and Victoire de Margerie
Pharmaceutics 2025, 17(7), 939; https://doi.org/10.3390/pharmaceutics17070939 - 21 Jul 2025
Viewed by 396
Abstract
Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, [...] Read more.
Background/Objectives: Hot-melt extrusion (HME) has become a key technology in pharmaceutical formulation, particularly for enhancing the solubility of poorly soluble Active Pharmaceutical Ingredients (APIs). While horizontal HME is widely adopted, vertical HME remains underexplored despite its potential benefits in footprint reduction, feeding efficiency, temperature control, and integration into continuous manufacturing. This study investigates vertical HME as an innovative approach in order to optimize drug polymer interactions and generate stable amorphous dispersions with controlled release behavior. Methods: Extrusion trials were conducted using a vertical hot-melt extruder developed by Rondol Industrie (Nancy, France). Acetylsalicylic acid (ASA) supplied by Seqens (Écully, France) was used as a model API and processed with Soluplus® and Kollidon® 12 PF (BASF, Ludwigshafen, Germany). Various process parameters (temperature, screw speed, screw profile) were explored. The extrudates were characterized by powder X-ray diffraction (PXRD) and small-angle X-ray scattering (SAXS) to evaluate crystallinity and microstructure. In vitro dissolution tests were performed under sink conditions using USP Apparatus II to assess drug release profiles. Results: Vertical HME enabled the formation of homogeneous amorphous solid dispersions. PXRD confirmed the absence of residual crystallinity, and SAXS revealed nanostructural changes in the polymer matrix influenced by drug loading and thermal input. In vitro dissolution demonstrated enhanced drug release rates compared to crystalline ASA, with good reproducibility. Conclusions: Vertical HME provides a compact, cleanable, and modular platform that supports the development of stable amorphous dispersions with controlled release. It represents a robust and versatile solution for pharmaceutical innovation, with strong potential for cost-efficient continuous manufacturing and industrial-scale adoption. Full article
(This article belongs to the Special Issue Advances in Hot Melt Extrusion Technology)
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42 pages, 4839 KiB  
Review
Cyclodextrins as Multifunctional Platforms in Drug Delivery and Beyond: Structural Features, Functional Applications, and Future Trends
by Iuliana Spiridon and Narcis Anghel
Molecules 2025, 30(14), 3044; https://doi.org/10.3390/molecules30143044 - 20 Jul 2025
Viewed by 955
Abstract
Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming inclusion complexes with various guest molecules, enhancing solubility, stability, and bioavailability. This review outlines the structural features of native CDs and their chemically modified derivatives, emphasizing the influence of functionalization on host–guest interactions. Synthetic approaches [...] Read more.
Cyclodextrins (CDs) are cyclic oligosaccharides capable of forming inclusion complexes with various guest molecules, enhancing solubility, stability, and bioavailability. This review outlines the structural features of native CDs and their chemically modified derivatives, emphasizing the influence of functionalization on host–guest interactions. Synthetic approaches for CD derivatization are summarized, with attention to recent developments in stimuli-responsive systems and targeted drug delivery. Analytical techniques commonly employed for characterizing CD complexes, such as spectroscopy, thermal analysis, and molecular modeling, are briefly reviewed. Applications in pharmaceutical formulations are discussed, including inclusion complexes, CD-based conjugates, and nanocarriers designed for solubility enhancement, controlled release, and site-specific delivery. Special consideration is given to emerging multifunctional platforms with biomedical relevance. The regulatory status of CDs is addressed, with reference to FDA- and EMA-approved formulations. Safety profiles and toxicological considerations associated with chemically modified CDs, particularly for parenteral use, are highlighted. This review presents an integrative perspective on the design, characterization, and application of CD-based systems, with a focus on translational potential and current challenges in pharmaceutical development. Full article
(This article belongs to the Special Issue Cyclodextrin Chemistry and Toxicology III)
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22 pages, 1787 KiB  
Article
Buffer pH-Driven Electrokinetic Concentration of Proteins in a Straight Microfluidic Channel
by Diganta Dutta, Xavier Palmer, Debajit Chakraborty and Lanju Mei
Surfaces 2025, 8(3), 52; https://doi.org/10.3390/surfaces8030052 - 18 Jul 2025
Viewed by 279
Abstract
We present a buffer-pH-modulated electrokinetic concentration strategy in MEMS microchannels that harnesses simple pH shifts to neutralize and charge proteins, reversibly “pausing” them at a planar electric-gate electrode by tuning to their isoelectric point (pI) and mobilizing them with slight pH offsets under [...] Read more.
We present a buffer-pH-modulated electrokinetic concentration strategy in MEMS microchannels that harnesses simple pH shifts to neutralize and charge proteins, reversibly “pausing” them at a planar electric-gate electrode by tuning to their isoelectric point (pI) and mobilizing them with slight pH offsets under an applied field. This synergistic coupling of dynamic pH control and electrode-gated focusing, which requires only buffer composition changes, enables rapid and tunable protein capture and release across diverse channel geometries for lab-on-chip, preparative, and point-of-care diagnostics. Moreover, it dovetails with established MEMS biomedical platforms ranging from diagnostics to drug delivery and microsurgery to gene and cell-manipulation devices. Future work on tailored electrode coatings and optimized channel profiles will further boost selectivity, speed, and integration in sub-100 µm MEMS devices. Full article
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