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Keywords = drug delivery applications

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22 pages, 5759 KiB  
Article
Poloxamer-Based Biomaterial as a Pharmaceutical Strategy to Improve the Ivermectin Performance
by Belén Alejandra Mezzano, Maria Soledad Bueno, Valeria Cintia Fuertes, Marcela Raquel Longhi and Claudia Garnero
Pharmaceutics 2025, 17(9), 1101; https://doi.org/10.3390/pharmaceutics17091101 (registering DOI) - 23 Aug 2025
Abstract
Background: Poloxamers are promising biomaterials for drug delivery applications due to their ability to enhance biopharmaceutical properties. Methods: This study focused on designing solid dispersions of ivermectin using poloxamer 407 by the fusion method and evaluating how variables of synthesis affect the polymer’s [...] Read more.
Background: Poloxamers are promising biomaterials for drug delivery applications due to their ability to enhance biopharmaceutical properties. Methods: This study focused on designing solid dispersions of ivermectin using poloxamer 407 by the fusion method and evaluating how variables of synthesis affect the polymer’s behavior and the resulting biopharmaceutical properties of ivermectin. Poloxamer 407 was selected based on a solubility test of preformulation studies. Initially, eight formulations were developed using different synthesis conditions, including polymer proportion, cooling gradient, and final process temperature. These were assessed by several characterization studies. Finally, saturation solubility dissolution profiles and in vitro drug release were also evaluated. Results: A combination of techniques confirmed the compatibility between poloxamer 407 and ivermectin in the solid dispersions. The rate of temperature in the cooling process of synthesis showed a significant impact on the polymer self-assembly, affecting their ability to entrap ivermectin. The optimized solid dispersion comprised ivermectin and poloxamer 407 in a 1:1 w/w ratio prepared by rapid cooling. This decrease in the crystallinity index and the nanometric size of particles of the solid dispersions could explain their ability to improve 1600-fold the aqueous solubility, as well as enhance the drug dissolution and in vitro drug release compared to pure ivermectin. Conclusions: Therefore, it follows that these poloxamer-based solid dispersions are promising alternatives to improve the bioavailability of ivermectin. Full article
(This article belongs to the Special Issue Biomaterials: Pharmaceutical Applications)
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44 pages, 2911 KiB  
Review
Molecularly Imprinted Polymer Nanoparticles for Pharmaceutical Applications: Sample Preparation, Sensor-Based Detection, and Controlled Drug Release
by Sibel Büyüktiryaki
Polymers 2025, 17(17), 2283; https://doi.org/10.3390/polym17172283 (registering DOI) - 23 Aug 2025
Abstract
Molecularly imprinted polymer nanoparticles (MIP NPs) are synthetic receptors with selective recognition sites for target molecules. They are employed instead of biorecognition elements in many applications due to their high affinity and selectivity, stability, easy preparation, and low cost. Their nanoscale size provides [...] Read more.
Molecularly imprinted polymer nanoparticles (MIP NPs) are synthetic receptors with selective recognition sites for target molecules. They are employed instead of biorecognition elements in many applications due to their high affinity and selectivity, stability, easy preparation, and low cost. Their nanoscale size provides enhanced surface interactions, faster response times, improved biocompatibility, and effective cellular penetration, particularly in complex biological environments. MIP NPs provide high selectivity and structural versatility in the sample preparation, sensor-based detection, and controlled drug delivery, serving as promising alternatives to conventional methods. This review highlights the recent advancements in the synthesis and application of MIP NPs in three critical areas: sample preparation, sensor-based detection, and controlled drug release. Additionally, recent developments in green synthesis approaches, biocompatible materials, and surface functionalization strategies that are effective in the performance of MIP NPs are mentioned. Full article
(This article belongs to the Special Issue Applications of Polymer Nanomaterials in Biomedicine)
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16 pages, 2237 KiB  
Article
CMC-Based Injectable Hydrogels Crosslinked by Diels–Alder Chemistry for Wound Healing Applications
by Israr Ali, Urwa Shahid, Seon-Hwa Kim, Suganthy Ramamoorthy, Won Han, Minseon Kim, Vishal Gavande, Won-Ki Lee, Joong Ho Shin, Sang-Hyug Park and Kwon Taek Lim
Gels 2025, 11(9), 674; https://doi.org/10.3390/gels11090674 (registering DOI) - 23 Aug 2025
Abstract
Chronic wounds disrupt natural healing and tissue regeneration, posing a major challenge in healthcare. Conventional wound care often lacks effective drug delivery, tissue integration, infection control, and patient comfort. However, injectable hydrogels offer localized, minimally invasive treatment and conform to irregular wound shapes. [...] Read more.
Chronic wounds disrupt natural healing and tissue regeneration, posing a major challenge in healthcare. Conventional wound care often lacks effective drug delivery, tissue integration, infection control, and patient comfort. However, injectable hydrogels offer localized, minimally invasive treatment and conform to irregular wound shapes. This study presents carboxymethyl cellulose (CMC)-based injectable hydrogels, prepared via Diels–Alder click chemistry using highly furan functionalized CMC (45%) and a bismaleimide crosslinker. The hydrogels showed a rapid gelation time (<490 s) under physiological conditions. The hydrogel exhibited favorable physicochemical and mechanical properties, as well as sustained curcumin release (∼80% in 5 days). In vitro studies confirmed excellent biocompatibility with NIH3T3 fibroblasts and notable antibacterial activity against E. coli, supporting its potential for wound healing applications. Full article
(This article belongs to the Special Issue Recent Advances in Crosslinked Gels (2nd Edition))
21 pages, 2057 KiB  
Review
A Comprehensive Review of Niosomes: Composition, Structure, Formation, Characterization, and Applications in Bioactive Molecule Delivery Systems
by Alfredo Amaury Bautista-Solano, Gloria Dávila-Ortiz, María de Jesús Perea-Flores and Alma Leticia Martínez-Ayala
Molecules 2025, 30(17), 3467; https://doi.org/10.3390/molecules30173467 (registering DOI) - 23 Aug 2025
Abstract
Niosomes are nanocarriers with a bilayer structure, consisting of a polar region and a non-polar region. This unique structure allows them to encapsulate compounds with varying polarities, addressing solubility challenges in the transport and delivery of bioactive molecules. The formation of niosomes involves [...] Read more.
Niosomes are nanocarriers with a bilayer structure, consisting of a polar region and a non-polar region. This unique structure allows them to encapsulate compounds with varying polarities, addressing solubility challenges in the transport and delivery of bioactive molecules. The formation of niosomes involves key structural, geometric, and thermodynamic factors influenced by the choice of surfactants and preparation methods. These factors, including the critical packing factor and the hydrophilic–lipophilic balance (HLB), play a crucial role in determining the properties of the final niosomes. Additionally, the use of Tandford’s equations allows for the calculation of geometric parameters. These factors determine the structural integrity and functional properties of niosomes, making it possible to design functional niosomes with characteristics tailored for specific applications. This ability to design niosomes with desired properties is especially valuable in biomedical fields, where precise control over drug delivery and targeting is essential. This review highlights the importance of niosome formulation and presents examples of niosomes that have been functionalized for specific applications, including anticancer treatments, immunological treatments, and their action in the central nervous system. Full article
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13 pages, 1103 KiB  
Article
Prolonged Gel Delivery to Oral Cavity from a Silicone Tube: In Vivo Assessment
by Suhail Alghanem, Ewelina Dziurkowska, Mateusz Lampkowski, Iwona Ordyniec-Kwaśnica and Małgorzata Sznitowska
Pharmaceutics 2025, 17(9), 1095; https://doi.org/10.3390/pharmaceutics17091095 - 22 Aug 2025
Abstract
Objectives: This study evaluated the comfort of using silicone tubes installed in the oral cavity as a reservoir for a hydrogel that allows for a slow delivery of the active substance acting locally or systemically. Methods: Perforated silicone tubes 8 cm [...] Read more.
Objectives: This study evaluated the comfort of using silicone tubes installed in the oral cavity as a reservoir for a hydrogel that allows for a slow delivery of the active substance acting locally or systemically. Methods: Perforated silicone tubes 8 cm long with two internal diameters were used: T1 (1.5 mm) and T2 (2.4 mm). The reservoirs were filled with hydrogel placebo formulations: carbomer 1.5% (C), hydroxyethylcellulose 4% (HEC), or hydroxypropylmethylcellulose (hypromellose) 3% (HPMC). Physical parameters of the gel were determined with a viscometer and a texture analyzer. During 4 h of application, the volunteers reported sensory perceptions, and the rate of gel erosion was evaluated. The results were correlated with the viscosity, rheology, and dissolution rate of the gels measured in vitro. Results: Volunteers reported only mild discomfort wearing the device, preferring smaller-sized tubes. The tubes were easy to apply and generally comfortable, with no reports of significant discomfort. Despite similar viscosity and rheology, the polymer type had a significant impact on erosion rate, both in vitro and in vivo. After 4 h of application in vivo, more than 90% of the carbomer gel remained in the tube, while in the case of less cohesive HPMC or HEC gels, this was about 50%. A statistically significant correlation was observed between the in vitro and in vivo mean erosion percentages for the HEC and HPMC gels. Conclusions: This study supports the use of silicone tubes as effective reservoir devices for prolonging the residence time of drug formulations in the oral cavity. Full article
(This article belongs to the Special Issue Development and Optimization of Buccal Films Formulations)
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20 pages, 891 KiB  
Review
Phytocannabinoids and Nanotechnology in Lung Cancer: A Review of Therapeutic Strategies with a Focus on Halloysite Nanotubes
by Dorota Bęben, Helena Moreira and Ewa Barg
Pharmaceuticals 2025, 18(9), 1244; https://doi.org/10.3390/ph18091244 - 22 Aug 2025
Abstract
Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including [...] Read more.
Lung cancer is the leading cause of cancer mortality worldwide, with a poor prognosis driven by late diagnosis, systemic toxicity of existing therapies, and rapid development of multidrug resistance (MDR) to agents such as paclitaxel and cisplatin. MDR arises through multiple mechanisms, including overexpression of efflux transporters, alterations in apoptotic pathways, and tumour microenvironment-mediated resistance. The application of nanotechnology offers a potential solution to the aforementioned challenges by facilitating the enhancement of drug solubility, stability, bioavailability, and tumour-specific delivery. Additionally, it facilitates the co-loading of agents, thereby enabling the attainment of synergistic effects. Halloysite nanotubes (HNTs) are naturally occurring aluminosilicate nanocarriers with unique dual-surface chemistry, allowing hydrophobic drug encapsulation in the positively charged lumen and functionalisation of the negatively charged outer surface with targeting ligands or MDR modulators. This architecture supports dual-delivery strategies, enabling simultaneous administration of phytocannabinoids and chemotherapeutics or efflux pump inhibitors to enhance intracellular retention and cytotoxicity in resistant tumour cells. HNTs offer additional advantages over conventional nanocarriers, including mechanical and chemical stability and low production cost. Phytocannabinoids such as cannabidiol (CBD) and cannabigerol (CBG) show multitarget anticancer activity in lung cancer models, including apoptosis induction, proliferation inhibition, and oxidative stress modulation. However, poor solubility, instability, and extensive first-pass metabolism have limited their clinical use. Encapsulation in HNTs can overcome these barriers, protect against degradation, and enable controlled, tumour-targeted release. This review examined the therapeutic potential of HNT-based phytocannabinoid delivery systems in the treatment of lung cancer, with an emphasis on improving therapeutic selectivity, which represents a promising direction for more effective and patient-friendly treatments for lung cancer. Full article
(This article belongs to the Special Issue Combating Drug Resistance in Cancer)
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16 pages, 3851 KiB  
Article
Lysozyme Amyloid for Synthetic RNA Delivery
by Benjamin Beluzo, Maytham Ismail, Sergei Chuikov, Venkateshwar G. Keshamouni and Mathumai Kanapathipillai
Pharmaceutics 2025, 17(9), 1094; https://doi.org/10.3390/pharmaceutics17091094 - 22 Aug 2025
Abstract
Background/Objectives: Lysozyme-based amyloid aggregates offer a promising platform for RNA delivery due to their stability, cationic nature, biocompatibility, and ability to form well-defined structures. In this study, we evaluated their potential as drug carriers, focusing on the delivery of polyinosinic–polycytidylic acid (Poly(I:C)), [...] Read more.
Background/Objectives: Lysozyme-based amyloid aggregates offer a promising platform for RNA delivery due to their stability, cationic nature, biocompatibility, and ability to form well-defined structures. In this study, we evaluated their potential as drug carriers, focusing on the delivery of polyinosinic–polycytidylic acid (Poly(I:C)), an immunostimulatory synthetic RNA. To validate RNA delivery capability and rule out the possibility that observed effects arose from the lysozyme–Poly(I:C) complex itself, small interfering RNA (siRNA) was also used to verify that the successful delivery of intact and functional RNA was the cause of the observed effects. Methods: The aggregates were characterized by particle size, zeta potential, morphology, and RNA encapsulation efficiency. Results: In vitro studies using RAW 264.7 macrophage-like cells demonstrated that Poly(I:C)-loaded aggregates improved RNA uptake and triggered significant immune activation without inducing toxicity. To further confirm the potential of lysozyme amyloids in RNA delivery, GFP siRNA-loaded aggregates were evaluated in A549-GFP cells. A notable decrease in GFP expression, confirmed through confocal microscopy and flow cytometry, confirmed successful intracellular delivery. Conclusions: These results highlight the potential of lysozyme amyloids as non-viral vectors for RNA delivery, with promising applications in immunotherapy. Full article
46 pages, 2116 KiB  
Review
Advances in the Application of Graphene and Its Derivatives in Drug Delivery Systems
by Changzhou Jin, Huishan Zheng and Jianmin Chen
Pharmaceuticals 2025, 18(9), 1245; https://doi.org/10.3390/ph18091245 - 22 Aug 2025
Abstract
Graphene, owing to its exceptionally high specific surface area, abundant surface functional groups, and outstanding biocompatibility, exhibits tremendous potential in the development of nanodrug delivery systems. This review systematically outlines the latest research advancements regarding graphene and its derivatives in drug loading, targeted [...] Read more.
Graphene, owing to its exceptionally high specific surface area, abundant surface functional groups, and outstanding biocompatibility, exhibits tremendous potential in the development of nanodrug delivery systems. This review systematically outlines the latest research advancements regarding graphene and its derivatives in drug loading, targeted delivery, and smart release. It covers delivery strategies and mechanisms for various types of drugs, including small molecules and macromolecules, with a particular emphasis on their applications in major diseases such as cancer, neurological disorders, and infection control. The article also discusses stimulus-responsive release mechanisms, such as pH-responsiveness and photothermal responsiveness, and highlights the critical role of surface functionalization of graphene and its derivatives in enhancing therapeutic efficacy while reducing systemic toxicity. Furthermore, the review evaluates key challenges to the clinical translation of graphene-based materials, including safety, toxicity, and metabolic uncertainties. It points out that future research should focus on integrating structural modulation of materials with biological behavior to construct intelligent nanoplatforms featuring biodegradability, low immunogenicity, and precise therapeutic targeting. The aim of this paper is to provide theoretical insights and technical guidance for the customized design and precision medicine applications of graphene and its derivative-based drug delivery systems. Full article
(This article belongs to the Section Pharmaceutical Technology)
34 pages, 4867 KiB  
Review
Polymeric Nanoparticles for Targeted Lung Cancer Treatment: Review and Perspectives
by Devesh U. Kapoor, Sonam M. Gandhi, Sambhavi Swarn, Basant Lal, Bhupendra G. Prajapati, Supang Khondee, Supachoke Mangmool, Sudarshan Singh and Chuda Chittasupho
Pharmaceutics 2025, 17(9), 1091; https://doi.org/10.3390/pharmaceutics17091091 - 22 Aug 2025
Abstract
Lung cancer remains a foremost cause of cancer-related impermanence globally, demanding innovative and effective therapeutic strategies. Polymeric nanoparticles (NPs) have turned up as a promising transport system for drugs due to their biodegradability, biocompatibility, and capability to provide controlled and targeted release of [...] Read more.
Lung cancer remains a foremost cause of cancer-related impermanence globally, demanding innovative and effective therapeutic strategies. Polymeric nanoparticles (NPs) have turned up as a promising transport system for drugs due to their biodegradability, biocompatibility, and capability to provide controlled and targeted release of therapeutic agents. This review offers a thorough examination of different polymeric NP platforms, such as chitosan, gelatin, alginate, poly (lactic acid), and polycaprolactone, highlighting their mechanisms, formulations, and applications in the treatment of lung cancer. These NPs facilitate the delivery of chemotherapeutic agents, gene therapies, and immune modulators, with enhanced bioavailability and reduced systemic toxicity. Additionally, advanced formulations such as ligand-conjugated, stimuli-responsive, and multifunctional NPs demonstrate improved tumor-specific accumulation and cellular uptake. The review also discusses quantum dots, magnetic and lipid-based NPs, and green-synthesized metallic polymeric hybrids, emphasizing their potential in theranostics and combination therapies. Preclinical studies show promising results, yet clinical translation faces challenges; for example, large-scale production, long-term toxicity, and regulatory hurdles. Overall, polymeric NPs represent a powerful platform for advancing personalized lung cancer therapy, with future prospects rooted in multifunctional, targeted, and patient-specific nanomedicine. Full article
(This article belongs to the Special Issue Nanoparticle-Mediated Targeted Drug Delivery Systems)
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25 pages, 2662 KiB  
Review
Recent Progress in Cellulose Nanofibril Hydrogels for Biomedical Applications
by Taeyen Won, MeeiChyn Goh, Chaewon Lim, Jieun Moon, Kyueui Lee, Jaehyeung Park, Kyeongwoon Chung, Younghee Kim, Seonhwa Lee, Hye Jin Hong and Kihak Gwon
Polymers 2025, 17(17), 2272; https://doi.org/10.3390/polym17172272 - 22 Aug 2025
Abstract
Cellulose nanofibril (CNF)-based hydrogels, owing to their sustainability, biocompatibility, and versatile mechanical properties, are promising for biomedical applications. This review analyzes the recent advances and biomedical applications of CNF hydrogels. CNF hydrogels can be prepared via physical and chemical crosslinking. Physical crosslinking involves [...] Read more.
Cellulose nanofibril (CNF)-based hydrogels, owing to their sustainability, biocompatibility, and versatile mechanical properties, are promising for biomedical applications. This review analyzes the recent advances and biomedical applications of CNF hydrogels. CNF hydrogels can be prepared via physical and chemical crosslinking. Physical crosslinking involves surface charge density control, pH manipulation, and flow-based processing to generate stable networks, whereas chemical crosslinking employs agents such as epichlorohydrin and citric acid to form permanent covalent bonds. These approaches enable precise control over hydrogel properties, including mechanical strength, porosity, and stimuli responsiveness. CNF hydrogels are particularly promising in drug delivery systems and tissue engineering. CNFs as drug delivery vehicles offer enhanced bioavailability and drug loading capacity owing to their open pore structure and large surface area. Recent developments in stimuli-responsive and injectable CNF hydrogels have enabled controlled drug release and improved targeting capabilities. Moreover, CNF hydrogels serve as effective scaffolds for cell growth and tissue regeneration, with applications in cartilage engineering and wound healing. Integrating CNF hydrogels with 3D bioprinting technology has generated complex tissue structures. However, several challenges remain, including the need for the standardization of toxicology assessments, optimization of large-scale production processes, and development of sophisticated control mechanisms for drug delivery. Future research should advance manufacturing technologies, improve long-term stability, and develop standardized testing protocols for regulatory compliance. Full article
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21 pages, 5297 KiB  
Article
Biological Effect of Green Synthesis of Silver Nanoparticles Derived from Malva parviflora Fruits
by Suzan Abdullah Al-Audah, Azzah I. Alghamdi, Sumayah I. Alsanie, Ibtisam M. Ababutain, Essam Kotb, Amira H. Alabdalall, Sahar K. Aldosary, Nada F. AlAhmady, Salwa Alhamad, Amnah A. Alaudah, Munirah F. Aldayel and Arwa A. Aldakheel
Int. J. Mol. Sci. 2025, 26(17), 8135; https://doi.org/10.3390/ijms26178135 - 22 Aug 2025
Abstract
The search for novel natural resources, such as extracts from algae and plant for use as reductants and capping agents for the synthesis of nanoparticles, may be appealing to medicine and nanotechnology. This study aimed to use Malva parviflora fruit extract as a [...] Read more.
The search for novel natural resources, such as extracts from algae and plant for use as reductants and capping agents for the synthesis of nanoparticles, may be appealing to medicine and nanotechnology. This study aimed to use Malva parviflora fruit extract as a novel source for the green synthesis of silver nanoparticles (AgNPs) and to evaluate their characterization. The results of biosynthesized AgNP characterization using multiple techniques, such as UV–Vis spectroscopy, scanning electron microscopy (SEM), FTIR analysis, and zeta potential (ZP), demonstrated that M. parviflora AgNPs exhibit a peak at 477 nm; possess needle-like and nanorod morphology with diameters ranging from 156.08 to 258.41 nm; contain –OH, C=O, C-C stretching from phenyl groups, and carbohydrates, pyranoid ring, and amide functional groups; and have a zeta potential of −21.2 mV. Moreover, the antibacterial activity of the M. parviflora AgNPs was assessed against two multidrug-resistant strains, including Staphylococcus aureus MRSA and Escherichia coli ESBL, with inhibition zones of 20.33 ± 0.88 mm and 13.33 ± 0.33 mm, respectively. The minimum bactericidal concentration (MBC) was 1.56 µg/mL for both. SEM revealed structural damage to the treated bacterial cells, and RAPD-PCR confirmed these genetic alterations. Additionally, M. parviflora AgNPs showed antioxidant activity (IC50 = 0.68 mg/mL), 69% protein denaturation inhibition, and cytotoxic effects on MCF-7 breast cancer cells at concentrations above 100 µg/mL. These findings suggest that M. parviflora-based AgNPs are safe and effective for antimicrobial and biomedical applications, such as coatings for implanted medical devices, to prevent biofilm formation and facilitate drug delivery. Full article
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35 pages, 2860 KiB  
Review
An Update on Novel Drug Delivery Systems for the Management of Glaucoma
by Harshilkumar S. Jani, Ketan Ranch, Radhika Pandya, Yashkumar Patel, Sai H. S. Boddu, Amit K. Tiwari, Shery Jacob and Haya Khader Ahmad Yasin
Pharmaceutics 2025, 17(8), 1087; https://doi.org/10.3390/pharmaceutics17081087 - 21 Aug 2025
Abstract
Glaucoma is recognized as a chronic optic neuropathy marked by progressive optic nerve degeneration, loss of retinal ganglion cells (RGCs, the neurons responsible for transmitting visual information from the eye to the brain), disruptions in optic disc blood supply, and changes in glial [...] Read more.
Glaucoma is recognized as a chronic optic neuropathy marked by progressive optic nerve degeneration, loss of retinal ganglion cells (RGCs, the neurons responsible for transmitting visual information from the eye to the brain), disruptions in optic disc blood supply, and changes in glial cell activation. It ranks as the second most prevalent cause of irreversible visual impairment worldwide and is a resultant of increased intraocular pressure (IOP). Addressing this condition proves complex due to the inherent hindrances posed by ocular barriers, which curtail the entry of drugs into the eye. Diverse carriers such as inorganic nanoparticles, polymeric nanocarriers, hydrogels, and contact lens-based systems with distinct physical and chemical attributes are being studied for drug delivery. They have shown enhanced ocular drug bioavailability through higher penetration across ocular tissues, prolonged retention in the precorneal space, sustained drug release, and targeted delivery to specific tissues. These ingenious delivery systems can be deployed through various administration routes—intravitreal or periocular injections or systemic administration—enabling the drugs to reach affected areas, aiding in the regeneration of compromised optical nerves. This review presents a comprehensive exploration of contemporary strides in ocular delivery formulations pertaining to glaucoma. This encompasses an examination of various nanocarrier typologies, delivery routes, in vitro and in vivo effectiveness, clinical applicability, and a forward-looking perspective into potential future developments. Full article
(This article belongs to the Special Issue Novel Approaches to Drug Delivery in Ophthalmic Disorders)
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15 pages, 1023 KiB  
Review
Stimuli-Responsive, Cell-Mediated Drug Delivery Systems: Engineering Smart Cellular Vehicles for Precision Therapeutics
by Samson Sitheni Mashele
Pharmaceutics 2025, 17(8), 1082; https://doi.org/10.3390/pharmaceutics17081082 - 21 Aug 2025
Abstract
Stimuli-responsive, cell-mediated drug delivery systems represent a dynamic interface between biological functionality and engineered control. Leveraging the inherent targeting properties of erythrocytes, immune cells, stem cells, and exosomes, these systems offer a promising strategy for precise therapeutic delivery. In this review, we provide [...] Read more.
Stimuli-responsive, cell-mediated drug delivery systems represent a dynamic interface between biological functionality and engineered control. Leveraging the inherent targeting properties of erythrocytes, immune cells, stem cells, and exosomes, these systems offer a promising strategy for precise therapeutic delivery. In this review, we provide a comprehensive analysis of the design principles and biological underpinnings of stimuli-responsive carriers that release payloads in response to endogenous triggers (e.g., pH, redox, enzymatic activity) or external stimuli (e.g., light, ultrasound, magnetic fields). We further examine current strategies for loading and functionalizing cellular carriers, highlight key therapeutic applications across oncology and regenerative medicine, and assess translational progress and regulatory challenges. This review underscores the emerging clinical potential of intelligent cell-based delivery vehicles and outlines future directions for their optimization and implementation. Full article
(This article belongs to the Special Issue Cell-Mediated Delivery Systems)
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28 pages, 1673 KiB  
Review
Advancement of 3D Bioprinting Towards 4D Bioprinting for Sustained Drug Delivery and Tissue Engineering from Biopolymers
by Maryam Aftab, Sania Ikram, Muneeb Ullah, Shahid Ullah Khan, Abdul Wahab and Muhammad Naeem
J. Manuf. Mater. Process. 2025, 9(8), 285; https://doi.org/10.3390/jmmp9080285 - 21 Aug 2025
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Abstract
The transition from three-dimensional (3D) to four-dimensional (4D)-bioprinting marks a significant advancement in tissue engineering and drug delivery. 4D-bioprinting offers the potential to more accurately mimic the adaptive qualities of living tissues due to its dynamic flexibility. Structures created with 4D-bioprinting can change [...] Read more.
The transition from three-dimensional (3D) to four-dimensional (4D)-bioprinting marks a significant advancement in tissue engineering and drug delivery. 4D-bioprinting offers the potential to more accurately mimic the adaptive qualities of living tissues due to its dynamic flexibility. Structures created with 4D-bioprinting can change shape in response to internal and external stimuli. This article reviews the background, key concepts, techniques, and applications of 4D-bioprinting, focusing on its role in tissue scaffolding and drug delivery. We discuss the limitations of traditional 3D-bioprinting in providing customized and sustained medication release. Shape memory polymers and hydrogels are examples of new responsive materials enabled by 4D-bioprinting that can enhance drug administration. Additionally, we provide a thorough analysis of various biopolymers used in drug delivery systems, including cellulose, collagen, alginate, and chitosan. The use of biopolymers in 4D-printing significantly increases material responsiveness, allowing them to react to stimuli such as temperature, light, and humidity. This capability enables complex designs with programmable shape and function changes. The expansion and contraction of hydrogels in response to temperature changes offer a practical method for controlled drug release. 4D-bioprinting has the potential to address significant challenges in tissue regeneration and medication administration, spurring ongoing research in this technology. By providing precise control over cell positioning and biomaterial integration, traditional 3D-bioprinting has evolved into 4D-bioprinting, enhancing the development of tissue constructs. 4D-bioprinting represents a paradigm shift in tissue engineering and biomaterials, offering enhanced possibilities for creating responsive, adaptive structures that address clinical needs. Researchers can leverage the unique properties of biopolymers within the 4D-printing framework to develop innovative approaches for tissue regeneration and drug delivery, leading to advanced treatments in regenerative medicine. One potential future application is in vivo tissue regeneration using bioprinted structures that can enhance the body’s natural healing capabilities. Full article
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15 pages, 1141 KiB  
Article
Enhanced Transdermal Delivery of Lidocaine Hydrochloride via Dissolvable Microneedles (LH-DMNs) for Rapid Local Anesthesia
by Shengtai Bian, Jie Chen, Ran Chen, Shilun Feng and Zizhen Ming
Biosensors 2025, 15(8), 552; https://doi.org/10.3390/bios15080552 - 21 Aug 2025
Viewed by 61
Abstract
Microneedles represent an emerging transdermal drug delivery platform offering painless, minimally invasive penetration of the stratum corneum. This study addresses limitations of conventional lidocaine hydrochloride formulations, such as slow onset and poor patient compliance, by developing lidocaine hydrochloride-loaded dissolvable microneedles (LH-DMNs) for rapid [...] Read more.
Microneedles represent an emerging transdermal drug delivery platform offering painless, minimally invasive penetration of the stratum corneum. This study addresses limitations of conventional lidocaine hydrochloride formulations, such as slow onset and poor patient compliance, by developing lidocaine hydrochloride-loaded dissolvable microneedles (LH-DMNs) for rapid local anesthesia. LH-DMNs were fabricated via centrifugal casting using polyvinyl alcohol (PVA) as the matrix material in polydimethylsiloxane (PDMS) negative molds, which imparts high mechanical strength to the microneedles. Biocompatibility assessments showed negligible skin irritation, resolving within 3 min. And drug-loading capacity reached 24.0 ± 2.84 mg per patch. Pharmacodynamic evaluation via mouse hot plate tests demonstrated significant analgesia, increasing paw withdrawal latency to 36.11 ± 1.62 s at 5 min post-application (p < 0.01). The results demonstrated that the LH-DMNs significantly elevated the pain threshold in mice within 5 min, surpassing the efficacy of conventional anesthetic gels and providing a rapid and effective solution for pain relief. These findings validate the system’s rapid drug release and efficacy, positioning dissolvable microneedles as a clinically viable alternative for enhanced transdermal anesthesia. Full article
(This article belongs to the Special Issue Advanced Microfluidic Devices and MEMS in Biosensing Applications)
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