Search Results (333)

Agomelatine (AG) is a novel antidepressant characterized by distinct mechanism of action and minimal side effects. However, extensive first-pass hepatic metabolism limits its clinical efficacy after oral administration, leading to low bioavailability (<5%). To get around these restrictions, the current study set out to create and assess a rectal thermosensitive in situ gel using biosynthesized AG-silver nanoparticles (AG-AgNPs). AG-AgNPs were successfully synthesized with gum acacia as a stabilizing agent, using silver nitrate as a precursor, and ascorbic acid as a reducing agent. The in situ gel formulation was optimized using a 3² factorial design, and then physicochemical, in vitro, and in vivo assessments were conducted. Nanoparticle formation was also evidenced by the appearance of a visible color change, UV-VIS, TEM, and XRD analysis techniques, which depicted spherical-shaped nanoparticles and a crystalline nature. The formulated optimized thermosensitive in situ gel showed good properties, which included drug content of 91.64%, gelation temperature of 26.63 °C, pH of 7.2, gel strength of 36.98 s, and sustained drug release of 80.24% in 6 h. The relative bioavailability in animal studies showed a remarkable increase in systemic availability with 277.5% relative bioavailability in comparison to an oral tablet formulation. In summary, results show that the AG-AgNP-loaded thermosensitive in situ gel could have potential use as a rectal delivery drug for bypassing first-pass effects and improving bioavailability for the drug Agomelatine. Full article

Temperature-responsive hydrogels are sophisticated stimuli-responsive biomaterials that undergo rapid, reversible sol–gel phase transitions in response to subtle thermal stimuli, most notably around physiological temperature. This inherent thermosensitivity enables non-invasive, precise spatiotemporal control of material properties and bioactive payload release, rendering them highly promising for advanced biomedical applications. This review critically surveys recent advances in the design, synthesis, and translational potential of thermo-responsive hydrogels, emphasizing nanoscale and hybrid architectures optimized for superior tunability and biological performance. Foundational systems remain dominated by poly(N-isopropylacrylamide) (PNIPAAm), which exhibits a sharp lower critical solution temperature near 32 °C, alongside Pluronic/Poloxamer triblock copolymers and thermosensitive cellulose derivatives. Contemporary developments increasingly exploit biohybrid and nanocomposite strategies that incorporate natural polymers such as chitosan, gelatin, or hyaluronic acid with synthetic thermo-responsive segments, yielding materials with markedly enhanced mechanical robustness, biocompatibility, and physiologically relevant transition behavior. Cross-linking methodologies—encompassing covalent chemical approaches, dynamic physical interactions, and radiation-induced polymerization are rigorously assessed for their effects on network topology, swelling/deswelling kinetics, pore structure, and degradation characteristics. Prominent applications include on-demand drug and gene delivery, injectable in situ gelling systems, three-dimensional matrices for cell encapsulation and organoid culture, tissue engineering scaffolds, self-healing wound dressings, and responsive biosensing platforms. The integration of multi-stimuli orthogonality, nanotechnology, and artificial intelligence-guided materials discovery is anticipated to deliver fully programmable, patient-specific hydrogels, establishing them as pivotal enabling technologies in precision and regenerative medicine. Full article

Injectable hydrogels (IHs) have gained considerable interest in biomedical and aesthetic applications due to their minimally invasive delivery, selective localization, and sustained release of bioactive agents. They exhibit flowability during administration and undergo in situ gelation under physiological conditions. These behaviors are influenced by their tunable structural, physical, mechanical, and viscoelastic properties, modulating performance. Rheological parameters, including viscosity (η), storage modulus (G′), loss modulus (G″), and yield stress (τ_y) of IHs with time (t), shear rate ($\stackrel{·}{\gamma }$), and frequency (f), explaining their shear thinning, thixotropy, viscoelasticity, and gelatin kinetics, serve as key quantitative indicators of their injectability, self-healing capability, and structural and mechanical stability. The rheological characteristics reflect molecular interactions and crosslinking mechanisms within IH networks, thereby linking formulation to provide overall performance, including injectability, biodegradability, and controlled release. This review summarizes recent advances in IHs for diverse applications, with a primary focus on their rheological properties. It also briefly addresses their composition, intermolecular interactions, and correlated function and performance. The applications discussed include hemostatic and wound dressings, tissue engineering and regenerative medicine scaffolds, drug delivery systems, reconstructive and aesthetic materials, and functional bioinks for 3D printing. Overall, this review demonstrates that rheological characterization provides an essential framework for the rational engineering of next-generation IH systems. Full article

This research successfully developed novel hydrogels composed of methacrylated dextran and inulin for targeted drug delivery in colorectal cancer therapy. The formulation exploits the natural degradation of both biopolymers by the large intestine’s microflora. A key achievement was the development of a room-temperature free radical polymerization synthesis method. The study thoroughly investigated how varying inulin content (10 and 20 wt%) influenced the hydrogels’ properties. The formulation with 20 wt% inulin exhibited the highest swelling ability at both pH 3 and pH 6, and consequently the lowest elastic modulus, measured by a newly established technique for granulated hydrogels. Using uracil as a model drug, in situ incorporated, confirmed that the greatest drug release occurs in the colorectal region for the neat dextran-based hydrogel, triggered by specific microbial enzymes. Notably, the addition of inulin did not enhance biodegradation-driven drug release in combination with dextran; instead, inulin primarily acted as a protective component against premature hydrolysis in the gastric medium. These findings strongly confirm that the targeted action is predominantly governed by the dextran component. The synthesized hydrogels, particularly the dextran-only formulation, therefore show strong potential as effective carriers for colon-targeted drug delivery. The primary objective of this study was to evaluate the feasibility of modified and unmodified dextran and inulin as biodegradable carriers for enzyme-triggered, colon-targeted drug delivery. Full article

Traditional drug delivery methods for gastrointestinal diseases, including oral and systemic administration, often suffer from degradation, inadequate mucosal absorption, and off-target toxicity. Consequently, these methods result in low bioavailability and suboptimal therapeutic outcomes for localized conditions such as inflammation and early-stage cancer. This review examines the innovative integration of advanced bioengineering platforms with therapeutic gastrointestinal endoscopy to address these delivery challenges. We concentrate on three principal bioengineered platforms: (1) nanoparticle systems (e.g., lipid, polymeric, and inorganic nanoparticles) designed for localized chemotherapy and theranostics; (2) in situ-forming hydrogels that serve as intelligent wound management materials and sustained drug depots; and (3) drug-eluting and biodegradable stents that convert passive luminal scaffolds into active, long-term drug-releasing devices. An analysis of these platforms demonstrates that their synergy with endoscopy facilitates precise, minimally invasive, and sustained local therapy, potentially transforming the treatment landscape for gastrointestinal diseases such as cancer and inflammatory bowel disease. Additionally, we investigate advanced strategies, including active targeting and stimulus-responsive release mechanisms, to enhance spatial precision. Despite promising preclinical advancements, clinical translation encounters challenges related to long-term biocompatibility, scalable manufacturing, regulatory pathways for drug-device combinations, and cost-effectiveness. Ultimately, the convergence of bioengineering and endoscopy presents significant potential to usher in a new era of precise, localized, and sustained micro-invasive treatments in gastroenterology. Full article

Isosorbide-based aliphatic polyesters are a promising class of biodegradable polymers for biomedical applications, representing an attractive alternative to poly(α-hydroxy acids). Derived from the bio-based bicyclic diol, they combine structural rigidity, tunable hydrophilicity, and enhanced biocompatibility, making them suitable for drug delivery and sustainable medical devices. In this study, we developed novel in situ forming implant (ISFI) formulations composed of poly(isosorbide sebacate) (PISEB) and dimethyl isosorbide (DMI), and evaluated their applicability for local delivery of doxycycline hyclate (DOXY), minocycline hydrochloride (MIN), and/or eugenol (EUG). Basic characteristics of new ISFI formulations were investigated. Rheological analysis demonstrated that the liquid formulations exhibited shear-thinning behavior, which is advantageous for ISFI systems. However, the MIN-loaded formulation exhibited excessively rapid drug release, with a pronounced initial burst (86.4 ± 5.9%) within 24 h, whereas the DOXY-loaded system showed a lower burst of 41.1 ± 5.9% over the same period. The effect of EUG addition on depot morphology and antibiotic release profiles was also assessed. In vitro drug release studies demonstrated that EUG reduced the release rate of both antibiotics, increasing and prolonging their antibacterial activity. Eugenol co-released with antibiotics also reduced the pro-inflammatory effect of the released antibiotic doses by more than tenfold. Full article

Ophthalmic drug delivery encounters unique challenges due to the anatomical and physiological ocular barriers, necessitating the development of novel drug delivery systems (NDDSs). This review focuses on emerging therapeutic platforms, including nanoemulsions (NEs), microemulsions (MEs), self-emulsifying drug delivery systems (SEDDSs) such as self-nano emulsifying drug delivery systems (SNEDDSs) and self-micro emulsifying drug delivery systems (SMEDDSs), emulgels, and in situ-forming emulgels, as novel strategies for enhancing ocular drug delivery. NEs and MEs, due to their small globule size, excellent drug solubility, stability, and bioavailability, offer promising solutions for effective ocular therapy. SEDDSs further enhance the stability and bioavailability of hydrophobic drugs through self-emulsification in aqueous environments. Emulgels, combining the benefits of emulsions and gels, provide sustained and controlled release of therapeutic agents, improving the ocular retention time and therapeutic efficacy. Additionally, in situ-forming emulgels offer the advantage of liquid-to-gel transition upon contact with ocular surfaces, optimizing drug delivery. The review discusses various ocular diseases, challenges for ocular delivery of conventional formulations, updates on emulsion-based novel drug delivery systems for ophthalmic drug delivery, mechanisms of enhanced ocular permeation, formulation strategies, advantages, and challenges, design-of-experiment considerations for optimization, characterizations, and recent advancements in these systems including patents and clinical trials, highlighting their potential for improving the treatment of various ocular diseases. Furthermore, this review explores marketed ophthalmic emulsions and future prospects for integrating these NDDSs into clinical ophthalmology, emphasizing their ability to overcome ocular barriers and enhance therapeutic efficacy. Full article

Gel-based delivery systems have emerged as versatile platforms in dentistry due to their biocompatibility, injectability, tunable rheology, and ability to localize therapeutic agents at the site of application. This review synthesizes current evidence on hydrogels, thermosensitive gels, mucoadhesive gels, nanoparticle-loaded gels, and stimuli-responsive systems, highlighting their structural characteristics, mechanisms of drug release, and clinical relevance. Mucoadhesive formulations demonstrate prolonged retention in periodontal pockets and oral mucosa, improving the efficacy of antimicrobials and anti-inflammatory agents. Thermosensitive gels enable minimally invasive administration and in situ gelation, supporting controlled release at body temperature. Nanoparticle-loaded gels exhibit enhanced drug stability and deeper tissue penetration, while “smart” gels respond to environmental stimuli such as pH or temperature to modulate release profiles. Clinical findings indicate reductions in probing depth, improved wound healing, decreased bacterial load, and better patient comfort when gel systems are used as adjuncts to mechanical therapy or regenerative procedures. However, despite these advances, challenges such as variability in gel stability, manufacturing reproducibility, regulatory approval pathways, and limited long-term clinical evidence still constrain widespread adoption of these systems in routine practice. Full article

Background: The potential of injectable hydrogels as drug depots lies in their ability to achieve local and sustained co-delivery of chemotherapeutic drugs and immunostimulants for combined tumor therapy. Method: In this study, we devised a localized chemo-immunotherapeutic strategy by co-loading the chemotherapeutic drug, oxaliplatin (OXA), and the immune-checkpoint blockade (ICB) antibody, anti-programmed cell death protein ligand 1 (anti-PD-L1), into a matrix metalloproteinase (MMP)-responsive injectable poly(L-glutamic acid) hydrogel (MMP-gel). Results: The in situ gelation of hydrogels enables local retention of OXA and model antibody IgG, as well as MMP-triggered sustained release. Meanwhile, the OXA-loaded MMP-gel caused the immunogenic cell death (ICD) of tumor cells. When administered intratumorally in mice carrying B16F10 melanoma, the MMP-gel co-loaded with OXA and anti-PD-L1 (OXA&anti-PD-L1@MMP-gel) demonstrated superior tumor suppression efficacy and prolonged the survival time of the animals with low systemic toxicity. Meanwhile, the OXA&anti-PD-L1@MMP-gel induced an increase in CD8⁺ T cells and M1 macrophages within tumors, and a decrease in Treg cells and M2 macrophages, demonstrating that the drug-loaded system enhanced the antitumor immune response. Moreover, the OXA&anti-PD-L1@MMP-gel effectively inhibited the growth of distal tumors in a bilateral-tumor experiment. Conclusions: Consequently, the responsive hydrogel-based chemo-immunotherapy holds potential in tumor treatment. Full article

Immune checkpoint inhibitors (ICIs) have revolutionized cancer immunotherapy by enhancing T-cell-mediated anti-tumor responses in solid malignancies. However, their efficacy is often limited by tumor-specific factors, T-cell dysfunction in cold tumors, or in the presence of lymph node metastasis (LNM). Moreover, clinical trials indicate no significant survival advantage of sentinel lymph node biopsy (SLNB) over no lymph node surgery in early-stage cancers, highlighting the need for novel combinatorial approaches to improve treatment outcomes. Tumor electrochemotherapy (ECT) can overcome immunosuppressive barriers in the tumor microenvironment by applying high electric fields that create transient micropores in cell membranes. This allows the enhanced uptake of chemotherapeutic drugs, resulting in increased cytotoxicity and the release of damage-associated molecular patterns (DAMPs). This triggers immunogenic cell death (ICD), a process that signals immune cells to attack cancer and promotes tumor regression. Considering advancements in lymphatic-targeted therapies and the immunostimulatory potential of uninvolved tumor-draining lymph nodes (TDLNs), TDLN-targeted ECT may act as an in situ cancer vaccination, activating immune cells within TDLNs through the release of DAMPs and serving as a hub to orchestrate systemic anti-tumor immunity. In patients with negative preoperative lymph node assessments, this approach may preserve lymph node integrity and lymphatic drainage while eradicating tumor cell colonies. When applied as neoadjuvant therapy before any TDLN treatment, TDLN-targeted ECT may leverage higher tumor-associated antigen loads, foster persistent immune memory, and reduce the risk of post-operative immune evasion. Full article

This study emphasizes overcoming the challenges of targeted drug delivery in colon cancer therapy by developing gastrointestinal (GI) stable, pectin-coated nanoliposomes for the oral delivery of Apigenin-Cyclodextrin Complex as an in situ gel formation. Initially, the formulation was strategically designed using design expert software for formulation optimization. FTIR and XRD studies were conducted to ensure physical compatibility and to confirm the encapsulation of apigenin within the formulation. In process optimization, among all seventeen formulations run tested, PNL (Api-Cy)-13 was identified for the highest drug loading, favourable size dimension of particle with zeta potential, and spherical external morphology through SEM analysis. The metered drug release during an in vitro study for PNL (Api-Cy)-13 was remarkably high (more than 75% of drug availability in the colonic environment, precisely in contrast to only 20% in the gastric phase in a sustained release manner), focused on colon drug targeting as an in situ gel. Furthermore, apigenin release from PNL (Api-Cy)-13 in an ex vivo chick ileum permeability study was observed both in the absence and presence of 1% vancomycin. An incremental apigenin release in the absence of the antibiotic (1% vancomycin) indicated gut microbial-associated and pectinase-mediated drug release. Here, pectin degradation materializes by the colonic microbial environment, which facilitates desirable incremental colonic drug permeation. Finally, an in vitro MTT assay and a competitive flowcytometric cell uptake study with PNL (Api-Cy)-13 using HCT-116 cells proved significant superiority in cytotoxicity profile for apigenin when delivered as an optimized coated nanoliposome in comparison to free apigenin or other non-modified nano-formulation. Also, the inhibition of the cell efflux process was validated by Multidrug Resistance 1 (MDR1) gene regulation. These observations establish an undoubted promise for the novel biopolymer, pectin-based apigenin-cyclodextrin nanoliposomes as targeted therapy in colon cancer with significant in vivo pharmacokinetics and safety profile. Full article

The cholinergic system is one of the most ancient and widespread signaling systems in the body, implicated in a range of pathological conditions—from neurodegenerative disorders to cancer. Given its broad relevance, there is growing interest in characterizing this system across diverse cellular models to enable drug screening, mechanistic studies, and exploration of new therapeutic avenues. In this study, we investigated four cancer cell lines: one of neuroblastoma origin previously used in cholinergic signaling studies (SH-SY5Y), one non-small cell lung adenocarcinoma line (A549), and two small cell lung carcinoma lines (H69 and H82). We assessed the expression and localization of key components of the cholinergic system, along with the cellular capacity for acetylcholine (ACh) synthesis and release. Whole-cell flow cytometry following membrane permeabilization revealed that all cell lines expressed the ACh-synthesizing enzyme choline acetyltransferase (ChAT). HPLC-MS analysis confirmed that ChAT was functionally active, as all cell lines synthesized and released ACh into the conditioned media, suggesting the presence of autocrine and/or paracrine ACh signaling circuits, consistent with previous reports. The cell lines also demonstrated choline uptake, indicative of functional choline and/or organic cation transporters. Additionally, all lines expressed the ACh-degrading enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), as well as the alfa seven (α7) nicotinic and M1 muscarinic ACh receptor subtypes. Notably, flow cytometry of intact SH-SY5Y cells revealed two novel findings: (1) ChAT was localized to the extracellular membrane, a feature not observed in the lung cancer cell lines, and (2) BChE, rather than AChE, was the predominant membrane-bound ACh-degrading enzyme. These results were corroborated by both whole-cell and surface-confocal microscopy. In conclusion, our findings suggest that a functional cholinergic phenotype is a shared feature of several carcinoma cell lines, potentially serving as a survival checkpoint that could be therapeutically explored. The discovery of extracellular membrane-bound ChAT uniquely in neuroblastoma SH-SY5Y cells points to a novel form of in situ ACh signaling that warrants further investigation. Full article

Background/Objectives: Neurogenic detrusor overactivity (NDO), caused by spinal cord injury or multiple sclerosis, is marked by involuntary bladder contractions and reduced urine volume. Current therapy requires frequent catheterization with oxybutynin hydrochloride. This work investigates a novel in situ forming implant (ISFI) with PLGA as a sustained-release formulation for the urinary bladder by quantifying drug release, polymer degradation, and solvent release in vitro. Methods/Results: Various formulation parameters were investigated, of which the drug load and PLGA termination were found to have the highest impact on drug release and polymer degradation. An increase in drug load from 1.5% to 7.5% for implants with the ester-terminated PLGA enhanced the degradation from 0% to around 20% after 7 d. Oxybutynin base catalyzed the polymer degradation, as implants with PLGA 502 and 15% drug load exhibited a degradation of 33% compared to 0% for 1.5% drug load. In the case of 1.5% drug load, the degradation could be increased by the use of an acid-terminated PLGA, compared to an ester-terminated. Conclusion: In summary, the feasibility of a biodegradable ISFI for NDO patients was shown, which could allow a single administration up to approx. one week, improving the quality of life for NDO patients. Additionally, this work provided insight to which formulation parameters can help to parallel drug release and polymer degradation. Full article

Background/Objectives: Lidocaine hydrochloride (LD-HCl) is the most commonly used local anesthetic in dentistry, often administered with epinephrine to extend its duration and reduce systemic absorption. However, its relatively short duration of action, the need for repeated injections, and the unpleasant taste may limit patient compliance and procedural efficiency. This study aimed to develop and evaluate a novel injectable nanoemulsion-based in situ gel depot system of LD to provide prolonged anesthetic activity. Methods: LD-loaded nanoemulsions were formulated by high-shear homogenization followed by probe sonication, employing Miglyol 812 N (oil phase), a combination of Tween 80 and soy lecithin (surfactant–co-surfactant), glycerin, and deionized water (aqueous phase). The selected nanoemulsion (S1) was dispersed in a thermoreversible poloxamer solution to form a nanoemulgel. The preparation was evaluated for globule diameter and uniformity, zeta potential, surface morphology, pH, drug content, stability, rheological behavior, injectability, and in vitro drug release. Analgesic efficacy was assessed via tail-flick and thermal paw withdrawal latency tests in Wistar rats. Cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements. Results: The developed nanoemulsions demonstrated a spherical shape, nanometer size (206 nm), high zeta-potential (−66.67 mV) and uniform size distribution, with a polydispersity index of approximately 0.40, while the nanoemulgel demonstrated appropriate thixotropic properties for parenteral administration. In vitro release profiles showed steady LD release (5 h), following the Higuchi model. In vivo studies showed significantly prolonged analgesic effects lasting up to 150 min (2.5 h) compared to standard LD-HCl injection (p < 0.001), with no adverse cardiovascular effects observed. Conclusions: The developed injectable LD in situ nanoemulgel offers a promising, patient-friendly alternative for prolonged anesthetic delivery in dental and operative procedures, potentially reducing the need for repeated injections and enhancing procedural comfort. Full article

Background/Objectives: Glioblastoma (GBM) is a fatal tumor in the central nervous system (CNS) with a poor prognosis. Preventing tumors from post-surgical recurrence is a significant clinical challenge, since current methods deliver chemotherapeutic agents in a rapid manner and are not effective against the residual tumor cells. To address these limitations, we develop a blue light-crosslinking hydrogel which can be rapidly gelled in situ and tightly adhere on the tissues for controlled chemotherapy, radiotherapy, and enhanced laser interstitial thermal therapy (LITT) to inhibit residual tumor cells from post-surgical recurrence. Methods: We utilize gelatin-MA based hydrogel with crosslinker VA-086 as hydrogel scaffold to encapsulate small-molecule drugs (Epirubicin and Cisplatin) and LITT agent polypyrrole-coated graphine oxide (PPy@GO). The mixture can form into hydrogel in situ by blue light irradiation and performed chemo-LITT and radio therapy simultaneously. Then we determine the prevailing factors that affect efficient encapsulation of therapeutic agents within hydrogels, efficiency of gelation, LITT enhancement, and drug release. Then evaluate efficiency in human cancer cells and an in vivo tumor model. Results: Our results demonstrate that 18 wt% Gelatin MA formulation achieved >95% gelation within 2 min, with drug-loaded gels forming within 5 min. The gelation can perform both in vitro and in vivo without affect the drug efficiency. This multi-treatment system can effectively prevent tumor recurrence and significantly prolong the medium survival of glioma-bearing (MBR-614 or U87-MGFL) mice to above 65 days compared with the control group (36 days). Conclusions: The results demonstrated promising effect of this system as a multi-therapeutic platform which combined chemo-LITT and RT. This synergistic strategy presents a new approach to the development of a local drug delivery system for the prevention of brain tumor recurrence. Full article