AAV-mediated multiple gene therapy combining VEGFA-targeting miR-agshRNAs and PEDF for the suppression of choroidal neovascularization.

The development of effective drug delivery systems for subcutaneous or intradermal injection requires systems with improved bioavailability and biocompatibility. Systematic physicochemical and biological interrogation of carnauba-wax/red-palm-oil lipid nanoparticles (LNPs) stabilized with d-α-tocopheryl-PEG-1000-succinate and polysorbate-40 shows that purposeful matrix engineering yields a robust sub-50nm carrier for under-skin delivery. Cryo-TEM and SAXS reveal hybrid morphology dominated by 30-40nm toroidal disc-shaped particles. Orthogonal analytics via multidetection asymmetrical flow field-flow fractionation and WAXS confirm that loading with quinine or dihydroartemisinin leaves size and crystallinity unchanged, achieving approximately 90% encapsulation efficiencies and particle stability up to 18 months at 4°C. Formulations containing red palm oil and the dual-surfactant corona exhibited reduced size dispersity compared with single-component formulations. Long-term viability assays in primary human fibroblasts and macrophages, and ex vivo cultured human skin, underscore excellent biocompatibility up to 0.024% (w/v) lipid. Fluorescein-labeled LNPs traversed the dermis and hypodermis, while only nanomolar lipid concentrations appeared in the receiver medium, indicating a sustained local depot. Overall, this study provides insights into the relationship between formulation composition, particle morphology and measured physicochemical and biological properties relevant to under-skin administration.

In situ-forming implants (ISFIs) based on poly(lactic-co-glycolic acid) (PLGA) offer a promising platform for long-acting parenteral drug delivery, enabling minimally invasive administration without surgical implantation. However, the development and clinical translation of PLGA-based ISFIs are hindered by formulation complexity, sensitivity to aterial variability, and limited predictability of drug release, particularly during early implant formation. Although previous reviews have described formulation components and release mechanisms, a comprehensive integration of Quality by Design (QbD) principles with a focus on risk prioritization remains absent. This review examines the application of QbD to solvent-exchange PLGA-based ISFIs, with an emphasis on identifying critical material attributes (CMAs) governing implant formation, burst release, and long-term release performance. Risk-based prioritization of CMAs and the role of design of experiments are systematically discussed. Special attention is given to burst release as a major CMA affecting safety, efficacy, and translational robustness. The evidence indicates that formulation-driven CMAs, such as polymer physicochemical properties, drug characteristics, and solvent selection, exert a greater influence on ISFI performance than process-related parameters. This review provides a structured perspective to support rational formulation design, improved reproducibility, and enhanced clinical translation of PLGA-based ISFI systems.

Chronic burn wounds remain a significant clinical challenge due to prolonged inflammation, delayed tissue regeneration, and limited effectiveness of current topical therapies. In this study, electrospun hyaluronic acid/poly(vinyl alcohol) (HA/PVA) nanofiber scaffolds loaded with Defactinib, a focal adhesion kinase inhibitor, were developed to promote burn wound healing through localized drug delivery. Optimized electrospinning conditions produced uniform, bead-free nanofibers with stable amorphous drug dispersion, as confirmed by SEM, TEM, XRD, and DSC analyses. The Defactinib-loaded nanofibers exhibited (DFT-NF) high drug entrapment efficiency, good hydrophilicity, and a biphasic release profile characterized by an initial burst followed by sustained release over 24 h. In a rat burn wound model, treatment with Defactinib-loaded nanofibers significantly accelerated wound closure compared with untreated and standard-treated groups. Non-invasive photoacoustic imaging enabled real-time monitoring of wound healing, revealing increased vascularity and improved tissue oxygen saturation in treated wounds by Day 21, indicative of enhanced vascular recovery. Histological evaluation further confirmed improved re-epithelialization, reduced inflammatory infiltration, and well-organized collagen deposition. Consistent with these findings, RT-PCR analysis showed marked suppression of key pro-inflammatory mediators (NF-κB, IL-1β, TNF-α, and IL-6) in the DFT-NF group, highlighting its potent anti-inflammatory activity. Overall, this study demonstrates that Defactinib-loaded HA/PVA nanofiber scaffolds, combined with imaging-based functional assessment, represent a promising and clinically relevant platform for advanced burn wound management.

Recently, lipid-polymer nanoparticles incorporating bile acids (BAs) have garnered significant interest in drug delivery research. Due to their amphiphilic nature, self-assembling properties, and steroid skeleton, BAs can serve as both drug-solubilizing and membrane-penetrating agents, facilitating drug transport across cell membranes. BAs exhibit diverse bioactivities, including anticancer, antimicrobial, and immunomodulatory effects, which further increase their potential for therapeutic applications. Their carboxyl and hydroxyl functional groups allow for easy derivatization, enabling the synthesis of a wide range of BA-based (macro)molecules. Introducing BAs into polymer systems leads to stable and biocompatible nanocarriers with high affinity to cell membranes, enabling the encapsulation, delivery, and controlled release of bioactive molecules. This review provides a comprehensive overview of polymers containing bile acids (BAs) as drug delivery vehicles. We first explore the biological roles and therapeutic potential of BAs. This is followed by a discussion of the synthetic strategies used to prepare polymers containing bile acid moieties. Finally, we assess the advantages and key challenges that will shape the future development of polymeric BA-based drug delivery systems.

Lung cancer is a highly malignant tumor with a poor prognosis. Exploring effective diagnostic and therapeutic approaches is of paramount importance. This study aims to develop a nanomedicine delivery system with dual capabilities for drug loading and magnetic resonance imaging (MRI), investigating its targeted drug delivery function and MRI tracking capability for lung cancer.
Method: This study prepared folate-targeted albumin magnetic nanoparticles for carboplatin encapsulation (FA-CBP-BMNs), characterized them, and determined the encapsulation efficiency, drug loading capacity, and release rate. Cellular function and MRI imaging capabilities were investigated via MTT assays, ICP-MS quantification, and cell capture experiments. In vivo tracking capability, antitumor effects, and biosafety were evaluated using a mouse model.
Results: The particle size of FA-CBP-BMNs was 186.37 ± 5.49 nm, with morphological analysis revealing spherical dispersion. The encapsulation efficiency and drug loading capacity were 12.25 ± 3.72% and 95.38 ± 4.19%, respectively. FA-CBP-BMNs exhibit sensitivity to the pH of the release medium, demonstrating enhanced sustained-release targeting properties in acidic environments. MRI imaging indicates that FA-CBP-BMNs improve relaxation efficiency. In vitro, they inhibit the proliferation of lung cancer cells. In vivo, they efficiently recognize and track tumor cells while exhibiting favorable antitumor effects, along with good biocompatibility and safety.
Conclusion: This study successfully developed a multifunctional targeted sustained-release drug delivery system, FA-CBP-BMNs, integrating drug loading and MRI imaging capabilities. FA-CBP-BMNs demonstrated significant advantages in targeted therapy and diagnosis of lung cancer, opening new avenues for its treatment and diagnosis with promising clinical application value.

Stimuli-responsive carbon nanotubes (CNTs) have emerged as transformative nanocarriers in precision oncology due to their unique physicochemical, optical, and mechanical properties, enabling controlled, targeted drug delivery. This review presents a comprehensive analysis of CNT-based systems engineered to respond to specific internal (pH, redox, and enzymatic) and external (light, temperature, magnetic, and ultrasound) stimuli for on-demand cancer therapy. The discussion covers synthesis methods, structural differences between single- and multi-walled CNTs, and diverse functionalization strategies that enhance solubility, biocompatibility, and stimuli responsiveness. The crucial advances in CNT-based delivery systems demonstrate their ability to achieve spatiotemporal control over drug release, improve tumour penetration, and minimize systemic toxicity through mechanisms such as pH-triggered drug detachment, GSH-mediated redox cleavage, and NIR-induced photothermal ablation. Integrating CNTs with polymers, peptides, and metal nanoparticles further enables multimodal applications, including chemo-photothermal, chemo-immuno, and gene therapies. Despite remarkable progress, challenges remain in understanding long-term pharmacokinetics, immunogenicity, and biodistribution, as well as in establishing standardized synthesis and regulatory frameworks. The review highlights emerging trends such as AI-driven CNT design, predictive pharmacokinetic modelling, and personalized nanomedicine, emphasizing their potential to revolutionize cancer treatment by achieving precise, adaptive, and patient-specific therapy.

Compound droplets of complex fluids (such as polymeric liquids) are becoming increasingly prominent for their applications in targeted drug delivery, cell and particle encapsulation, and many other micro- and millifluidic processes. Despite this, the morphological behaviors of such drops are yet to be properly addressed even in simple canonical flows. The main challenge in this regard perhaps originates from the complex and non-linear constitutive relation of the constituent fluids. To address this, here, we analyze the flow field and the deformations of a compound viscoealstic drop, subject to uniaxial extensional flows. All three phases are considered to obey the Giesekus constitutive model, known for its ability to accurately capture the rheological properties of many polymeric liquids. We derive asymptotic solutions for the limiting case of small deformation and weak viscoelasticity, and subsequently validate them against full numerical simulations based on the ternary phase field method. The results, derived mainly from the asymptotic analysis, demonstrate that the elongational elastic stresses help reduce the deformations in both the shell and the core, and this is facilitated by the shear-thinning nature and the finite extensibility of the Giesekus model. We also show that depending on the extent of viscoelasticity of the outermost phase and the core size, the shape of the shell may change from prolate to oblate and vice versa for the core. The viscoelasticity of the core on the other hand has relatively little influence on the deformation of the shell, although it is found to significantly impact the core's evolution.

Hydrogels are prevalent materials with applications ranging from drug delivery systems, contact lenses and tissue engineering scaffolds. However, they require considerable perturbation to observe their nanoscale, solution-phase structures necessary for predicting bulk properties. Although studies suggest that methylcellulose, a quintessential hydrogel material, can be described by a semiflexible biopolymer network model, there remain demonstrable inconsistencies in the predicted concentration dependence of rheological properties and in the observation of higher-order features. Here we image solvated hydrogels with high spatiotemporal resolution via liquid-phase transmission electron microscopy to avoid desolvation and shear artefacts. Corroborated by scattering and scanning electron microscopy, we observe that methylcellulose hydrogels form a network with high persistence length and micrometre-scale fibril bundles arranged in hierarchical assemblies, providing a more accurate prediction of bulk rheology. In addition, network structures are observed for hydroxypropyl methylcellulose and hydroxypropyl cellulose. These observations across multiple-length scales lead to a clearer understanding of how nanoscale structure impacts microscale structure and macroscopic behaviour, aiding the development of more accurate structure-property relationships for hydrogel materials.

Microwave Synthesis of Gold Nanoparticles in Poly(Ethylene Glycol)-Based Hydrogels for Drug Delivery

Cycloparaphenylenes (CPP) and their heteroatom-doped derivatives are emerging as interesting nanocarriers due to their adjustable electronic structures and π-conjugated frameworks. This study used density functional theory (DFT) to examine the structural, electrical, and adsorption characteristics of virgin CPP, nitrogen-doped CPP (N-CPP), and oxygen-doped CPP (O-CPP) in relation to two anticancer agents, hydroxyurea (HU) and thioguanine (TG). Geometry optimization verified the inherent stability of all carriers, whereas doping induced localized distortions that increased reactivity. Electronic tests indicated a consistent decrease in the energy gap after medication adsorption. HU functioned as a weak electron donor, resulting in little gap narrowing, whereas TG operated as a robust electron acceptor, causing substantial band-gap quenching-particularly in TG@O-CPP, where the gap practically disappeared, resulting in metallic-like behavior. Adsorption energies (−0.10 to −1.13 eV) and recovery periods revealed divergent kinetics: HU complexes desorbed almost quickly, while TG demonstrated more robust binding and extended residence lengths, especially on O-CPP. Charge-transfer research validated the contrasting donor–acceptor functions of HU and TG, supported by global reactivity indices indicating heightened electrophilicity and reduced hardness upon TG adsorption. The findings identify TG@O-CPP as the most promising system, with improved adsorption strength, substantial charge transfer, notable band-gap reduction, and adjustable electrical responsiveness. These results provide significant insights for the systematic design of CPP-based nanostructures in biosensing applications that need rapid reaction and in drug-delivery systems that require controlled release.

Polyethylene glycol (PEG)-capped gold nanoparticles (PEG-AuNPs) are of great interest for targeted drug and chemotherapy delivery due to their biocompatibility and ability to evade immune detection. However, repeated administration can trigger the accelerated blood clearance (ABC) phenomenon, reducing circulation time and altering pharmacokinetics. This study aimed to evaluate whether pretreatment with free PEG before PEG-AuNP administration could improve pharmacokinetic behavior and mitigate the ABC effect, compared to PEG-AuNPs alone.

AuNPs were synthesized via the Turkevich-Frens method, PEGylated, and characterized using ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), zeta potential (ZP) analysis, and transmission electron microscopy (TEM). The PEG-AuNPs were spherical with a core diameter of 19.54 ± 1.758 nm. To assess the effect of free PEG, two groups of rats received an initial dose of PEG-AuNPs; both were given a second dose, but only the second group was pretreated with free PEG. Gold concentrations in plasma and organs were quantified using a validated inductively coupled plasma mass spectrometry (ICP-MS) method, and pharmacokinetic parameters were determined.

The ABC index confirmed the ABC phenomenon when comparing the first and second PEG-AuNP doses. Unexpectedly, pretreatment with free PEG did not significantly affect pharmacokinetic parameters (Cmax, tmax, t0.5; p > 0.05) compared to non-pretreated animals. Notably, PEG-AuNP accumulation in the liver and spleen increased approximately six- to sevenfold and two- to threefold, respectively, after the second dose, consistent with ABC-associated organ uptake.

In conclusion, under the current experimental conditions, pretreatment with free PEG before the second PEG-AuNP dose did not significantly mitigate the ABC phenomenon, indicating that additional strategies may be required to overcome immune recognition and enhance the pharmacokinetic performance of PEGylated nanocarriers.

This study scrutinizes the effect of thermal radiation and Stefan blowing on the chemical reactive flow of Boger nanofluid across a stretched sheet with Darcy Forchheimer medium and heat generation using an intelligent computational framework based on Artifice neural network-Bayesian regularization. Furthermore, Brownian motion and thermophoresis properties have been examined. The suggested model of how Stefan blowing affects the chemical reactive flow of a Boger nanofluid with thermophoresis effects and Brownian motion has useful applications in a number of industrial and engineering operations. In chemical reactors, nano-coating technologies, and polymer processing, this model is essential for improving heat and mass transport processes. While the Boger nanofluid model accurately depicts non-Newtonian behaviour pertinent to biofluids and complex lubricants, Stefan blowing consideration offers insights on evaporation or suction effects. For the purpose of maximizing nanoparticle dispersion in cooling systems, fuel cells, and medicinal devices like targeted drug delivery systems where exact control over particle motion and chemical reactivity is crucial, Brownian motion and thermophoresis are also critical. The velocity profile improves as the Stefan blowing parameter values rise, but the thermal and concentration profiles decrease.

Precision tumor theranostic in minimally invasive interventions still face challenges such as poor navigational flexibility and limited functional integration. Here, we present a 2.5 mm magnetic-driven multifunctional optoelectronic catheter (MDMOC) fabricated via 3D multi-axis printing for in situ tumor mapping and therapy. The MDMOC integrates magnetic navigation, targeted drug delivery, localized photodynamic therapy, X-ray trackable imaging, and multiplexed biosensing of metabolites and ions. Its magneto-optical-electric-fluid multimodal design enables navigation through complex pathways, simultaneously monitoring biomarkers across the tumor microenvironment and delivering localized therapy. In rabbit and mouse tumor models, the MDMOC distinguished tumor from normal tissue, guided precise therapy, and minimized systemic side effects. In a Bama pig model, it achieved accurate navigation, multiparametric sensing, and targeted contrast agent delivery in complex anatomy. By integrating diagnostic and therapeutic functions with remote magnetic control, the MDMOC provides a versatile platform for real-time, precision-guided tumor diagnosis and therapy.

Over 15% of acne patients manifest moderate to severe clinical presentations, accompanied with bacterial infection, long-term inflammatory responses, dysregulated lipid metabolism, and post-acne skin atrophy. Although microneedles (MNs) represent an effective transdermal drug delivery system for acne treatment, the therapeutic effects on the restoration of dysregulated lipid metabolism and the prevention of atrophic acne scars are still lacking. Herein, we develop proteoglycan-mimetic comb polymer (HMC)-based dissolving microneedles (HMC-PEP MNs) with encapsulation of therapeutic peptides. This system effectively targets the acne pathophysiological pathways involving bacterial colonization, lipid dysregulation, chronic inflammation and impaired tissue repair. Specifically, HMC enables sustained release of antimicrobial and anti-inflammatory peptides via multiple non-covalent interactions. HMC-PEP MNs display significant efficacy via eradicatingCutibacterium acnes infection, suppressing pro-inflammatory mediator expression, and reducing the TREM2/M2 macrophage ratio. Integrated transcriptomic and metabolomic analysis reveals that HMC-PEP MNs effectively regulate cholesterol and linoleic acid metabolism, inhibit pro-inflammatory signaling transduction, and reduce keratinocyte proliferation and differentiation by inhibiting the IGF1/IGF1R/PI3K/AKT/mTOR signaling pathway. Interestingly, HMC-PEP MNs also promote collagen synthesis and ameliorate fibroblast dysfunction, thereby preventing the formation of post-acne dermal atrophy. This study presents an effective therapeutic strategy for acne and elucidates the underlying mechanisms of HMC-PEP MNs, demonstrating considerable promise for clinical translation.

This study investigates the efficacy of co-assembled, physically cross-linked nanocarriers comprising tannic acid (TA) and a P(DMAEMA-co-OEGMA) random/statistical double-hydrophilic copolymer for ovalbumin (OVA) encapsulation. TA-based nanocarriers, prepared at varying TA molar ratios (10% w/v and 20% w/v), exhibited nanoaggregates of different sizes, as revealed by dynamic light scattering, with Nanocarrier 1 system showing populations of 11 and 109 nm, while Nanocarrier 2 formed a single population of 75 nm in size. Notably, both colloidal systems demonstrated stability under thermal treatment and resilience to changes in salt concentrations higher than 0.15 M, but disassembly phenomena in basic media. Utilizing these nanocarriers for OVA loading via electrostatic interactions revealed strong positive charges (~30 mV) for all protein-loaded nanocarrier cases. In particular, they demonstrated sizes within the desired range (Rh = 96–118 nm) and considerable stability over 20 days and in the presence of serum proteins. Overall, this study underscores the importance of physical cross-linking as a viable strategy for the formation of tunable nanometric hydrocolloids for effective protein encapsulation, with significant implications for drug delivery systems.

Microfluidic technologies have emerged as powerful tools in pharmaceutical sciences, offering precise control over fluid handling, mixing, and mass transfer at the microscale. These unique characteristics have enabled significant advances in controlled pharmaceutical formulation and drug screening, addressing key limitations of conventional bulk-scale methods, such as poor reproducibility, high material consumption, and limited physiological relevance. This review provides a comprehensive overview of recent progress in microfluidics for pharmaceutical applications, with a focus on formulation control, nanocarrier and advanced drug delivery system fabrication, controlled release, and stability enhancement. The role of microfluidic platforms in high-throughput and physiologically relevant drug screening, including cell-based and organon-chip models, is critically discussed. Furthermore, the integration of microfluidics with emerging technologies such as automation, artificial intelligence, digital microfluidics, and advanced analytical tools is highlighted as a driver of datadriven and continuous pharmaceutical development. Key challenges related to scalability, standardization, regulatory acceptance, and ethical considerations are also examined. Finally, future perspectives emphasize the growing translational potential of microfluidics in continuous manufacturing, personalized medicine, and precision therapeutics. Overall, this review underscores the transformative impact of microfluidic technologies on modern pharmaceutical formulation and drug screening, positioning them as integral components of next-generation drug development pipelines.

Design and Development of Standardized Ginger (Zingiber officinale) Extract in Self Nano Emulsifying Drug Delivery Systems (SNEDDS) Formulation

The orthodontic landscape is currently witnessing a significant technological evolution with the emergence of direct 3D-printed aligners (DPAs), which promise to close the digital workflow loop by eliminating the geometric limitations and solid model waste inherent to traditional thermoformed clear aligners (TCAs). This review provides a comprehensive analysis of the material science governing this transition from inert thermoplastic sheets to reactive photocurable resins. We explore the fundamental chemistry of DPA materials, and the pivotal role of post-processing in ensuring mechanical integrity and biocompatibility. Beyond passive mechanics, this review highlights preclinical research in functional material engineering, detailing how experimental DPAs are being investigated for the integration of antibacterial agents, remineralization fillers, and drug delivery systems. Furthermore, we evaluate the limited but emerging clinical data on DPAs, contrasting their shape-memory properties and force delivery profiles with conventional appliances, while critically addressing emerging safety concerns regarding monomer elution and microplastic generation. We conclude that while DPA technology offers superior dimensional control, comprehensive life cycle assessments and long-term in vivo trials are essential to fully substantiate their clinical efficacy, overall sustainability, and potential as advanced orthodontic appliances.

Rational control over polymer surface chemistry is central to designing nanocarriers with predictable stability and intracellular trafficking. Here, we report a modular materials strategy based on poly(succinimide) to elucidate how balanced cationic functionality governs nanocarrier assembly, colloidal robustness, and nanobio interfacial interactions. Amphiphilic polymer derivatives were prepared by sequential conjugation of oleyl chains and cationic headgroups to generate three nanocarrier variants containing guanidinium and choline, choline only, or guanidinium only. Systematic physicochemical characterization revealed that cooperative guanidinium-choline conjugation is essential for colloidal stability in physiological media. In contrast, guanidinium-only nanocarriers suffer from rapid aggregation. Cellular uptake studies demonstrated that guanidinium-choline surface chemistry dictates rapid, energy-independent membrane translocation and preferential nuclear localization, while others internalized via clathrin-mediated endocytosis and remain lysosomally sequestered. Leveraging this accelerated nuclear drug delivery enables amplified cancer cell apoptosis. The direct translocation capability further facilitated rapid penetration into three-dimensional (3D) tumor spheroids, highlighting the importance of surface charge balance for transport across multicellular barriers. Collectively, this study establishes cationic conjugation balance as a parameter that links polymer design to nanocarrier stability, cellular entry mechanism, and intracellular targeting capabilities.