Water-in-water emulsions as versatile platforms for controlled drug release systems: A scoping review

Migraine is a disabling neurological condition, which must undergo fast and prolonged therapeutic management but this is often hampered by low bioavailability, first-pass degradation and gastrointestinal upheaval during the migraine episodes with the conventional method of administration in oral form as the antimigraine agents. Tryptans (zolmitryptan and frovatriptan) are commonly employed in the treatment of acute migraine but these pharmacokinetic shortcomings diminish their efficacy. Transdermal drug delivery system (TDDS) has been a new way of offering an option because it evades hepatic metabolism, leads to better systemic absorption and offers a control of drug release. This is a critical review of transdermal strategies that are worked out to deliver zolmitriptan and frovatriptan, including formulation design, drug release, skin permeability, and pharmacodynamics. Recently, it has been shown that zolmitryptan has been tested exhaustively on the basis of sophisticated nano-vesicular systems especially niosomal transdermal patches, which is based on the application of surfactants and cholesterol to augment drug encapsulation, lipid fluidization, and transdermal incursion. Such systems have biphasic release profiles, enhanced bioavailability as well as high modulation of migraine-related biomarkers in preclinical models, which show greater therapeutic potential. Transdermal preparations of frovatriptan on the other hand have mainly been concerned with standard polymeric matrix patches that are usually based on hydrophilic and hydrophobic polymers. Even though these systems are predictable and sustained drug release systems, they show poor skin permeation, and no complete in vivo pharmacodynamics and mechanistic assessment are shown. In general, comparative analysis indicates that nano-vesicular transdermal delivery systems have certain unique benefits to conventional polymeric patches in attaining quick onset of action, better skin penetration and better treatment effect of migraine. The results show that there are important gaps in the existing research on the use of frovatriptan transdermal and indicate that new carrier-based formulations and carefully designed clinical trials are needed to maximize transdermal antimigraine products.

Wound infection causes excessive inflammation, delays healing, and may lead to severe complications. An ideal dressing should release antibacterial agents on demand to eradicate pathogens locally. Enzyme-responsive drug release systems are highly biocompatible and specific, yet their application in chitosan hydrogels has been limited by imprecise control over release profiles, mechanical properties, and potential drug resistance from premature leakage. Herein, we developed a dual-enzymatically responsive chitosan hydrogel for the on-demand release of antibacterial nanoparticles (ANPs). By synthesizing a series of hydroxyphenyl- and N-acetyl-modified glycol chitosan (HPPA-GC), we tuned the hydrogel stiffness and lysozyme degradation kinetics. Broad-spectrum ANPs were encapsulated via photo-cross-linking. Lysozyme, abundant in infected wounds, triggered hydrogel degradation and ANP release in vitro. When applied to S. aureus-infected full-thickness wounds in mice, the ANP-loaded hydrogel effectively combated infection and accelerated healing. This study demonstrates a robust and biocompatible platform for enzyme-triggered antimicrobial delivery, showing promise for the future development of smart wound dressings.

Natural polysaccharides in colloidal drug delivery systems for brain glioma therapy: Mechanisms and advancements.

The purpose of this study was to investigate the characteristics of sustained drug release systems established by polylactic acid (PLLA)/RGD/mitomycin C (MMC) electrospun nanofiber membrane in vitro, and confirm its anti-scarring effect in a rabbit model of glaucoma filtration surgery (GFS). In vitro experiments: (1) PLLA/RGD/MMC nanofiber membrane drug delivery system was prepared by electrospinning technology. (2) Characterization of nanofiber membrane. (3) Biocompatibility detection of nanofiber membrane. In vivo experiment: construct a surgical model for rabbit eye GFS, divided into four groups: the control group, the PLLA/RGD membrane group, the 0.4 mg/mL MMC group, and the PLLA/RGD/MMC membrane group. The morphology of filtering blebs and wound healing were observed on the 7th, 14th, and 28th days after the operation. At 28 days after the operation, histological and immunohistochemical staining were performed to observe the scar formation. Finally, the results were statistically analyzed. The composition, structure, hydrophily, thermal behaviors, degradability, and mechanical properties of the membrane were investigated in detail. In vitro cell culture assay indicated that the PLLA/RGD/MMC2 membrane could release MMC in a sustained manner for over 25 days. In vitro cell culture assay proved the superior cytocompatibility of the membrane with Human embryonic Tenon's capsule fibroblasts (HFTFs). Histology and immunohistochemistry indicated that the membrane could efficiently inhibit scaring formation after GFS and showed significant advantage over the conventional MMC cotton pad. The as-prepared PLLA/RGD/MMC membrane could be a potential candidate for inhibiting scaring formation after GFS in the future. This work shed some light to the developments and applications of MMC loaded electrospinning membrane for inhibiting postoperative fibrosis in GFS.

Titanium (Ti) is one of the most widely used implant materials; however, postoperative failures still frequently occur due to its poor osseointegration and limited antibacterial performance. The key to accelerating bone healing and improving implantation success lies in modulating immune responses through the regulation of immune cell behaviors. In this work, simvastatin, which is reported to have the immune regulation function was loaded into photothermal TiO 2 nanotubes (diameter 60–65 nm) formed on the Ti surface and subsequently covered with an intelligent thermosensitive chitosan hydrogel (phase transition temperature 38.95 °C) to construct a light-controlled drug release system (SCTH@rNT). The release of simvastatin from TiO 2 nanotubes was precisely regulated under near-infrared (NIR) irradiation. In vitro, the SCTH@rNT + NIR system exhibited remarkable antibacterial activity, reducing the viable colonies of S. aureus and E. coli by 98.6% and 97.4%, respectively, and significantly promoting osteogenic differentiation, with alkaline phosphatase (ALP) activity 1.8-fold higher than that of the control on day 14. The controlled release further enabled immunomodulation by upregulating Interleukin-10 (IL-10) expression 2.3-fold and down-regulating Tumor Necrosis Factor-alpha (TNF-α) by 48%, thereby alleviating inflammation. In vivo, the system reduced inflammatory cell infiltration by 62.7% and markedly enhanced new bone formation. Overall, this light-controlled drug delivery platform effectively creates a favorable immune microenvironment by dynamically regulating the macrophages behaviors, showing great potential for clinical translation in improving the integration and longevity of Ti-based implants.

This review aims to examine the impact of three-dimensional (3D) printing technologies on enhancing psychiatric pharmacotherapy through facilitating personalized and patient-centered drug delivery. This research specifically addresses problems such as poor medication compliance, polypharmacy, and palatability issues, especially in pediatric and elderly populations. A thorough review of the literature was conducted, focusing on novel advances in 3D printing techniques, including fused deposition modeling (FDM), semisolid extrusion (SSE), stereolithography, inkjet printing, binder jetting, and selective laser sintering (SLS). Selected research highlighted the application of such technologies in developing customized oral drug dosage forms. Emphasis was placed on the exploitation of polymers like Eudragit® E PO, flavor-masking excipients, and their combination with biosensor and artificial intelligence (AI) systems. Case studies were assessed to ascertain their relevance and innovation in the development of psychiatric medications. 3D printing allows the manufacture of tailored psychiatric drugs with greater dosing versatility, taste masking, and the ability to merge several active drug ingredients into a single pharmaceutical form. Patient-friendly dosage forms such as chew gummies and chocolate tablets demonstrated enhanced acceptability. Also, forthcoming technologies such as 4D printing and AI-driven biosensors yield intelligent, interactive drug release systems that are specific to individual physiological or behavioral inputs. 3D printing represents a paradigm-shifting advance in psychiatric care, offering solutions to long-standing treatment compliance and fixed-dose challenges. Although regulatory and scalability challenges persist, the intersection of pharmaceutical engineering, material science, and artificial intelligence creates an encouraging platform for the future of precision mental care therapies.

Long-term controlled in vitro release of FITC-dextran using polymer-based drug delivery systems manufactured by semi-solid extrusion 3D printing.

Light-responsive coumarin-functionalised nanogels for metformin delivery.

Tissue Reconstruction and Drug Release System Utilizing Natural Polymer-Based Biomaterial Silk Fibroin: An Analysis Based on Traditional Chinese Medicine

To provide expert recommendations for side effect management in patients with bladder cancer receiving intravesical-drug releasing system (iDRS) treatment and for optimizing iDRS insertion procedure success. Indwelling iDRS are designed to provide sustained local exposure to therapy. In clinical trials, frequent side effects of iDRS treatment were lower urinary tract symptoms (LUTS) (e.g., dysuria, pollakiuria, micturition urgency), urinary tract infections (UTIs), and hematuria. These side effects are generally low grade, but if not properly managed, may lead to treatment interruptions or discontinuations. As data are limited, practical recommendations based on expert opinion for the management of common side effects and best practices for iDRS insertion procedures may improve treatment adherence and optimize outcomes in patients with bladder cancer receiving iDRS. Two separate expert panels were convened to develop recommendations for side effect management with iDRS and optimizing iDRS insertion procedure success. Stepwise treatment-specific management strategies for LUTS, UTIs, and hematuria in patients receiving iDRS treatment that are familiar to practicing urologists are presented, including considerations for continuation or discontinuation of iDRS treatment. Several advanced techniques can be considered to improve iDRS insertions based on variations in patient anatomy.

Balanced biocompatibility in high-viscosity hydroxypropyl methylcellulose-based sponge containing nanoconfined silver citrate nanoparticles.

Sustainable synthesis and characterization of inulin/fructans-based polyurethane hydrogels using deep eutectic solvents for drug delivery systems.

Implant-associated complications-including infection, adverse immune responses, and poor tissue integration-pose significant risks to patients, often leading to implant failure, revision surgeries, or chronic disease. Current chemical-based strategies, such as antibiotic or drug-releasing systems, are limited by short-term efficacy, narrow therapeutic windows, and potential toxicity. Surface topography offers a promising alternative, but most designs target single cell types and overlook the complex, multicellular dynamics at the implant-host interface. Here, a new multifunctional platform is introduced based on nano-micro hybrid wrinkled topographies fabricated via a custom nanofabrication method that combines layer-by-layer (LbL) self-assembly with mechanical nanomanufacturing. This system simultaneously modulates bacteria, immune cells, and tissue progenitors to enable antibacterial activity, immune regulation, and tissue regeneration. On hybrid surfaces, nanoscale features disrupt bacterial adhesion (>50% biofilm reduction vs. flat controls), while microscale features enhance macrophage polarization (≈3-fold increase in M2 markers) and osteogenic differentiation (>8-fold increase in ALP activity), indicating strong pro-healing responses. Notably, macrophages exhibit context-dependent behavior-driving inflammation during bacterial infection and repair in its absence-creating an immune-balanced microenvironment for implant integration.The modular nature of this platform allows expansion to other cell types and disease contexts, offering a broadly applicable strategy for next-generation biomaterials.

Osteoarthritis (OA) is a common degenerative joint disease, and early diagnosis and effective treatment are essential for managing its progression. This study focuses on the development of a novel drug delivery system using aggregation-induced emission (AIE) probe for enhanced fluorescence imaging and targeted therapy in OA. TPE-S-BTD, an AIE probe, is synthesized and characterized for its photophysical properties, demonstrating significant aggregation-induced fluorescence enhancement. FPTD (FA-PEG-DSPE@TPE-S-BTD@DS) nanomicelles, which encapsulate TPE-S-BTD and diclofenac sodium (DS), are designed to target M1 macrophages via folate (FA) receptor-mediated endocytosis. These nanomicelles are incorporated into methacrylanhydride-modified hyaluronic acid (HAMA) hydrogel microspheres using microfluidic technology, creating a sustained drug release system (HAMA@FPTD). In vitro and in vivo experiments demonstrated the ability of this system to target M1 macrophages, reduce inflammation, and enhance cartilage repair in an OA rat model. This approach shows promise for the treatment and imaging of OA through a minimally invasive strategy, utilizing both FA-mediated targeting and controlled drug release.

Cancer stem cells (CSCs) and myeloid-derived suppressor cells (MDSCs) contribute to chemoresistance and immunosuppression, constraining chemoimmunotherapy outcomes. Differentiation therapy, aiming to mature CSCs and MDSCs, shows great promise. However, its efficacy is hindered by limited accessibility in hypoxic deep tumor regions. Inspired by the apoptotic body (ApoBD)-mediated deep tumor penetration, we design a pulsatile sequential drug release system with a core-shell structure. The reversible acid-responsive shell protonates and swells in lysosomes to release doxorubicin, inducing lysosomal escape and cell apoptosis. In ApoBDs, it deprotonates and contracts to prevent excessive drug release. After deep penetration via ApoBDs, the hypoxia-responsive core releases all-trans retinoic acid to reverse CSCs and MDSCs, overcoming chemoresistance and modulating the immuno-microenvironment. This strategy targets the heterogeneous distribution of CSCs and MDSCs in solid tumors, enhancing chemo-intervention and immune checkpoint blockade therapy while presenting encouraging potential for cascade deep tumor penetration and differentiation therapy.

Double emulsions (DEs) are widely explored in pharmaceuticals due to their ability to encapsulate both hydrophilic and hydrophobic drugs. However, their inherent instability limits their effectiveness in controlled drug delivery. Double emulsion capsules (DECs), formed by encapsulating DEs within a polymer shell, improve structural stability but still suffer from unintended drug diffusion due to the porous nature of polymeric shells. Polydopamine (PDA), a bioinspired polymer known for its strong adhesion, biocompatibility, and chemical stability, is a promising coating material for biomedical applications. However, research on its coating on DECs and its potential impact on passive leakage remains underexplored. Here we report PDA-coated DECs as an on-demand drug release system. The PDA coating effectively reduces passive leakage by forming an additional PDA layer on the DEC surface. Under optimized coating conditions, the passive leakage of coated DECs is ~ 20% lower than that of uncoated DECs for 8days. Also, on-demand drug release is demonstrated through the photothermal effect of PDA, which enables localized heating under NIR laser irradiation. This study highlights PDA-coated DECs as a versatile drug delivery platform with enhanced stability, tunable release properties, and photothermal activation, making them promising for targeted drug delivery, implantable therapeutics, and precision medicine.

Abstract Malignant melanoma, a highly aggressive malignancy, necessitates innovative therapeutic strategies integrating biomaterial innovation with multimodal treatment modalities. Herein, we report the development of a collagen-derived bioelectronic skin (c-ADM) nanoengineered via interfacial assembly of porcine acellular dermal matrix (ADM)—a natural collagen-rich scaffold—with conductive poly (3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) and copper sulfide nanoparticles (CuS-NPs). This hybrid system synergizes photothermal ablation, stimuli-responsive drug delivery, and electrostimulation (ES) for comprehensive postoperative melanoma management and tissue regeneration. The c-ADM platform exhibits superior mechanical robustness, enzymatic resistance, and biocompatibility, enabling real-time motion monitoring while maintaining structural integrity in dynamic physiological environments. Leveraging the photothermal efficiency of CuS-NPs, localized hyperthermia (ΔT > 40 °C) under near-infrared (NIR) irradiation induces irreversible melanoma cell apoptosis. Concurrently, laser-triggered temperature-responsive drug release enables synchronized photothermal-chemotherapy, with sustained doxorubicin release profiles at tumor sites. Notably, pH-responsive Cu2⁺ liberation from CuS-NPs facilitates intelligent functional switching: bactericidal activity at tumor microenvironment pH (5.0–6.0) and pro-regenerative effects under physiological pH (7.4) for wound healing. In vitro/in vivo assessments confirm c-ADM’s dual therapeutic efficacy including ES-enhanced cancer cell death via mitochondrial dysfunction and accelerated full-thickness skin regeneration through collagen remodeling and angiogenesis modulation. This work establishes a collagen-based bioelectronic scaffold for personalized oncological care, integrating intraoperative tumor eradication, postoperative surveillance, and adaptive tissue reconstruction. Graphic Abstract

Characterization, antibacterial property, biocompatibility, and optimization of novel composite nanofibers incorporating curcumin-loaded flexible nano-liposomes.

Introduction: Bioprosthetic heart valves (BHV) are commonly used to replace diseased heart valves but face limited durability due to calcification. Deleterious immune responses are involved in BHV calcification, but the underlying mechanisms remain poorly understood. This study aims to elucidate the unrevealed mechanisms and explore new therapeutic strategies. Hypothesis: Immune-modulatory target engagement through precision therapeutic strategies could constitute a novel paradigm for addressing BHV Calcification Methods: Infiltration of immune cells was determined in clinical calcified BHV specimens and mouse models. Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST-seq) were integrated to resolve cellular heterogeneity and pathological progression in BHV calcification. Immunodeficient mouse models were employed to identify pivotal immune subsets. Conditional knockout mice and cell experiments were used to validate mechanistic pathways. Two clinically translatable therapeutic strategies were developed: a local sustained drug release system using layer-by-layer assembly was developed for clinical translation. Results: The spatiotemporal cell atlas revealed macrophages as the dominant immune population in calcified BHVs. Depletion of macrophages alleviated BHV calcification, while the absence of T and B cells had no significant effect. A novel Acod1lo pro-calcification macrophage subset was identified, exhibiting diminished itaconate production. The loss of Acod1/itaconate exacerbated macrophage apoptosis, oxidative stress, and extracellular matrix disruption through the HIF-1α-glycolysis pathway, ultimately leading to BHV calcification. Restoring itaconate via localized release systems suppressed BHV calcification in mouse models. Conclusions: This study pioneers the application of scRNA-seq and ST-seq to decode the immune landscape of BHV calcification, identifying Acod1lo macrophages as central mediators. Itaconate supplementation effectively suppresses calcification via modulating macrophage metabolism, leading to the development of novel strategies to reduce BHV calcification by modulating the immune response.