Nanoemulsions (NEs) are promising delivery systems for lipophilic active ingredients. However, traditional preparation methods of NEs are energy-intensive, complex, and lead to poor stability and high costs. This study aims to introduce a novel Pre-Nanoemulsions (PNEs) system to overcome the limitations of traditional nanoemulsion preparation methods. The PNEs, composed of an oil phase, surfactant, co-surfactant, and aqueous phase, form thermodynamically stable isotropic mixtures. The optimized PNEs were characterized in terms of particle size, zeta potential, and polydispersity index (PDI). Comprehensive stability tests, including centrifugation, dilution, and long-term storage, were conducted. Turbiscan analysis was also performed to further assess their stability. Additionally, the sustained release and transdermal absorption capabilities of the PNEs were evaluated. The optimized PNEs exhibited a particle size of 115.8 ± 2.6 nm, zeta potential of -40.4 ± 2.4 mV, and PDI of 0.15 ± 0.02, with high encapsulation efficiency for lipophilic substances. Comprehensive stability tests, including centrifugation, dilution, and long-term storage, demonstrated robust performance, which was further confirmed by Turbiscan analysis. The PNEs also showed enhanced sustained release and transdermal absorption capabilities. This universal PNEs system provides a simple, low-cost, and efficient solution for delivering lipophilic active ingredients. It addresses the key challenges of traditional nanoemulsions and offers significant potential for practical applications across various industries.

Objective Inorganic nanocrystals represent a transformative platform for targeted drug delivery, offering unique physicochemical properties derived from their crystalline cores. However, clinical translation is contingent upon sophisticated surface engineering to navigate biological barriers, ensure colloidal stability, and achieve precision targeting. Significance of review This review critically examines the synergistic convergence of biocompatible coatings and bio-orthogonal chemistry as a paradigm shift in nanocrystal surface design. We systematically analyze advanced coating materials including polymeric (PEG, zwitterions, poly(2-oxazoline)), protein-based, and lipid architectures that establish stealth coronas against opsonization and immune clearance. Concurrently, we evaluate bio-orthogonal methodologies (SPAAC, IEDDA) enabling site-specific, catalyst-free conjugation of targeting ligands under physiological conditions. Key findings The integration of these approaches facilitates stimuli-responsive smart nanocrystals capable of logic-gated activation within pathological microenvironments. Conclusion We further address translational challenges including long-term biocompatibility, scalable manufacturing, and regulatory pathways, proposing design principles for next-generation nanotherapeutics where interfacial chemistry dictates biological destiny.

ABSTRACT Objective: To study the synergistic anticancer efficacy of Andrographolide (AG), a bioactive phytochemical with immunomodulator properties, and paclitaxel (PTX), a frontline chemotherapeutic agent, when administered as co-loaded nanoemulsion, to enhance therapeutic outcome with minimal adverse effect. Significance: The proposed nanoemulsion is expected to achieve synergistic anticancer effects, and minimize systemic toxicity. Key findings: Cytotoxic potential of AG and PTX at various molar concentrations using Chou-Talalay method were determined. A synergistic ratio (1:1) was identified and used as coloaded nanoemulsion. The system was optimized for particle size, zeta potential and encapsulation efficiency. Thermal and spectral characterization techniques were employed to evaluate drug identity and compatibility, while HPLC-based analytical method was developed for simultaneous quantification of AG and PTX in % entrapment and drug release samples. Further evaluated for MTT test, cell uptake study, scratch migration test, apoptosis and cell cycle arrest. Tumour regression test confirmed therapeutic efficacy and acute toxicity test ensure the safety of developed formulation. The AG-PTX nanoemulsion exhibited enhanced cellular uptake, cell apoptosis, and cell-cycle arrest in vitro compared to monotherapies. In vivo studies using a syngeneic tumour (invasive mammary carcinoma) bearing mouse model demonstrated significant tumour regression (10-fold), improved and reduced systemic toxicity, as shown by stable body weight and histopathological assays. Conclusion: Co-delivery of AG and PTX via targeted nanocarrier offers a promising dose reduction strategy to circumvent the dose limiting toxicity of PTX while maintaining/enhancing its anticancer efficacy. Further, the findings suggest a translational potential for AG as a chemosensitizer in combination therapy regimens.

Objective Green synthesis of zinc oxide (ZnO) nanoparticles (NPs) using the aqueous extract of fruit waste, investigating their antioxidants, antimicrobial, anticancer, and wound healing properties. Significance: This study presents an eco-friendly synthesis of ZnO NPs that repurpose organic fruit waste, contributing to sustainable practices in nanomaterial production. The potential applications of ZnO NPs as antioxidant, antimicrobial, and anticancer agents, as well as their role in wound healing are explored. Methods ZnO NPs were synthesized using the aqueous extract of fruit waste, and were characterized using UV-visible spectroscopy, DLS, XRD, FTIR and SEM-EDX. Antioxidant activity was measured using the DPPH assay. Cytotoxicity was assessed on A549 lung carcinoma cells, and antimicrobial activity was tested against Staphylococcus aureus and Pseudomonas aeruginosa. A gel formulation containing chitosan and Aloe vera (CS-AV)/ZnO NPs was evaluated for wound healing in an infected wound model. Results The synthesized ZnO NPs exhibited nanoscale size, good colloidal stability, and polygonal morphology. They demonstrated strong antioxidant activity, dose-dependent cytotoxicity against A549 cells, and significant antibacterial effects. Incorporation of ZnO NPs into the CS-AV gel markedly enhanced wound healing, achieving complete wound closure by day 21. Histopathological analysis further confirmed improved tissue regeneration, as evidenced by reduced inflammation, increased fibrosis, and well-developed collagen formation. Conclusion Fruit waste-derived ZnO nanoparticles offer promising antimicrobial, antioxidant, anticancer, and wound healing properties.

Objective This study aimed to enhance the in vitro digestion and permeability of β-carotene (BC), a lipophilic antioxidant with therapeutic potential in oxidative stress-related disorders, by developing a nanostructured lipid carrier (NLC) system based on medium-chain fatty acids (MCFAs). Significance Although BC exhibits strong antioxidant activity, its poor solubility and low gastrointestinal absorption limit clinical use. This study addresses these barriers by formulating a novel medium-chain fatty acid-based NLC using ethanol injection method that improves BC’s solubility, permeability, and bioactivity. The approach offers a scalable oral promising platform for antioxidant therapies targeting chronic diseases linked to oxidative stress. Methods BC-loaded NLC (BC-NLC) was prepared via ethanol injection and subsequently optimized using a Box–Behnken design. Physicochemical properties, biopharmaceutical performance, and antioxidant effects were evaluated. Results The optimized BC-NLC showed a particle size of 153.9 nm, polydispersity index of 0.29, zeta potential of −14.1 mV, and encapsulation efficiency of 62.0%. In vitro digestion revealed 63-fold and 38-fold increases in BC micellar efficiency in simulated gastric and intestinal fluids, respectively. A 9.1-fold enhancement in intestinal transport was observed. Stability testing confirmed >88% BC retention over 28 days at 5 °C. Antioxidant assays demonstrated ≥2.3-fold higher radical scavenging activity and a 22.7-fold increase in reducing power compared to free BC. Conclusions The MCFAs-based BC-NLC effectively overcomes key biopharmaceutical limitations, offering enhanced in vitro digestion, stability, and antioxidant efficacy. It represents a promising oral delivery strategy for oxidative stress-related therapeutic applications.

Objective A transdermal iontophoretic formulation for sumatriptan was approved by the U.S. FDA in 2013 for patients who cannot take oral medications. However, it was withdrawn in 2020 due to skin burns and scarring associated with prolonged electrical applications. This study aimed to determine whether short-duration, low-current iontophoresis can still achieve therapeutically effective plasma concentrations of sumatriptan. Significance Developing a safe, rapid-acting transdermal delivery system would provide an alternative treatment option for patients who cannot tolerate oral medications, while reducing the risk injury caused by long-term electrical exposure. Methods The target plasma concentration in rats was calculated from rat elimination pharmacokinetics and previously reported human therapeutic concentrations. Rats received 0.04, 0.2, or 0.4% sumatriptan gel on the abdominal skin, and iontophoresis was applied at 0.05, 0.1, or 0.2 mA/cm2 for 2 h. Plasma concentrations were measured over time. An additional experiment applied 0.2 mA/cm2 for 0.5 h followed by 0.1 mA/cm2 for 0.5 h. Results Based on the maximal plasma concentration after oral administration in humans (16.5 ng/mL), the target plasma concentration in rats was calculated as 0.94 µg/mL. The 0.2 and 0.4% formulations at 0.1 mA/cm2 exceeded this target within 1.5 and 1.0 h, respectively. The 0.2% formulation at 0.2 mA/cm2 surpassed the target within 0.5 h and maintained it for 3 h. Conclusions Short-duration, low-current iontophoresis effectively achieved therapeutic plasma concentration of sumatriptan. These findings support the potential of this approach as a safer transdermal alternative for patients unable to take oral medications.

Objective This study focused on improving the delivery of tectoridin, an anti-alcoholic compound from Pueraria flower, which suffers from poor solubility and low bioavailability when taken orally. To address this, we designed a biomimetic liposome system that targets the liver by harnessing the body’s natural bile acid transport pathways. Significance Successful clinical translation of many insoluble natural products, including tectoridin, is limited by their unfavorable pharmacokinetics. A liver-targeted strategy utilizing physiological transporters offers a promising means to enhance hepatic delivery and therapeutic efficacy, thereby addressing a critical hurdle in the development of plant-derived pharmaceuticals. Methods Following bioactivity-guided isolation and identification of tectoridin, cholic acid-functionalized liposomes (LPs-tectoridin) were designed to actively target hepatocyte-specific transporters (NTCP/OATPs). The formulation was optimized and characterized for particle size, encapsulation efficiency, and in vitro dissolution. Pharmacokinetic, tissue distribution, and pharmacodynamic evaluations were performed in a rat model of ethanol-induced intoxication and liver injury. Results The optimized liposomes exhibited a mean particle size of 157.55 ± 0.23 nm, a high encapsulation efficiency (>85%), and significantly improved the dissolution rate of tectoridin. In vivo, LPs-tectoridin increased the oral bioavailability (AUC0–24) by 2.11-fold and enhanced hepatic accumulation by 3-fold compared to free tectoridin. The formulation demonstrated superior anti-intoxication and hepatoprotective effects, notably reducing serum ALT and AST levels by 49.95% and 35.20%, respectively, and elevating hepatic SOD activity by 2.04-fold. Conclusions This study not only confirms tectoridin as a principal anti-alcoholic constituent but also establishes a robust liver-targeted liposomal platform that harnesses intrinsic bile acid transport pathways. The strategy significantly improves the solubility, bioavailability, and therapeutic performance of tectoridin, offering a viable approach for enhancing the delivery of poorly soluble natural products in drug development.

ABSTRACT Objective The goal of this study was to create and optimize a topical cream based on cubosomes for improved dermal delivery and stability of ferulic acid, a strong antioxidant with anti-hyperpigmentation properties that is limited by low photostability and skin permeability. Significance Improving the stability of ferulic acid and regulating its skin distribution is crucial for its successful application in cosmeceutical formulations. Cubosomal nanocarriers offer a viable way to enhance photostability, solubility, and sustained release, improving therapeutic efficacy while preserving skin safety. Methods Glyceryl monooleate and Poloxamer 407 were used to create ferulic acid-loaded cubosomes. The effects of almond oil and Sepineo P600 on viscosity and drug content were assessed using the Box-Behnken design to optimise cream formulation. Particle size analysis, entrapment efficiency, FT-IR, DSC, XRD, and rheological investigations were all part of the characterisation. To clarify release mechanisms, kinetic models were fitted to in vitro release data. Tyrosinase inhibition studies evaluated the effectiveness of anti-hyperpigmentation, while MTT and RT-PCR assays were used to assess biocompatibility. Results The optimised formulation developed nanosized particles with thixotropic flow behaviour, skin-compatible pH, and high entrapment efficiency. Diffusion-controlled delivery was indicated by release following first-order and Higuchi kinetics, although super case-II transport was suggested by Korsmeyer-Peppas analysis(n = 1.105). The cream showed moderate tyrosinase inhibition, TNF-α expression suppression, and non-cytotoxic behaviour. Conclusion Ferulic acid’s potential as a safe and efficient cosmeceutical for skin-brightening applications is supported by the cubosomal cream’s significant improvements in solubility, photostability, and prolonged dermal application.

Objective To review emerging long-acting drug delivery and implantable systems developed to overcome the limitations of conventional intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). Significance of review nAMD is a leading cause of irreversible vision loss worldwide. Although intravitreal anti-VEGF injections are clinically effective, their short intraocular half-life necessitates frequent administration, resulting in high treatment burden, poor patient compliance, and increased risk of procedure-related complications. Long-acting injectable and implantable drug delivery systems offer a promising approach to maintain therapeutic drug levels while reducing injection frequency and healthcare burden. Key findings Recent advances in controlled-release technologies, including electrospun nanofibers, injectable microcapsules, core-shell nanofibers, 3D-printed implants, dip-cast tubular devices, nanostructured thin-film systems, suprachoroidal implants, encapsulated cell technologies, and gene therapy-based approaches, demonstrate sustained drug release ranging from several weeks to over 1 year. These platforms provide improved drug stability, higher payload capacity, tunable release kinetics, and favorable biocompatibility. Clinically validated refillable implants, such as Susvimo™, confirm the feasibility of long-term intraocular anti-VEGF delivery. Conclusions Next-generation long-acting ocular drug delivery systems have the potential to transform nAMD management by reducing invasive procedures, improving patient adherence, and maintaining durable therapeutic efficacy. Continued optimization and clinical translation of these technologies are essential for their successful integration into routine ophthalmic care.

Objective This review systematically summarizes the mechanisms and applications of friction as both endogenous and exogenous stimuli in drug delivery systems (DDSs). Significance Intelligent DDS can respond to endogenous or exogenous stimuli to achieve accurate drug delivery, so it has become a hot spot in pharmaceutical research. Therefore, friction, as a novel physical stimulus, offers unique potential to overcome physiological barriers and improve targeted therapy, providing new strategies for DDS design. Method This article systematically reviews the two forms of stimulation of friction in drug delivery and its mechanism. In terms of endogenous effects, the focus was on exploring the regulatory effects of physiological friction, such as biological friction shear, cellular micro friction, eyelid corneal friction, and joint friction on drug delivery, revealing how frictional stimulation triggers drug release or enhances targeting through mechanical signals. In terms of exogenous effects, the promoting mechanism of mechanical friction on transdermal DDSs and the intracellular drug delivery technology driven by frictional nanogenerators were analyzed. Results This review outlines friction-triggered drug release mechanisms and their therapeutic potential, highlighting superior spatiotemporal precision for dynamic tissues over traditional systems, yet notes key translational challenges including parameter standardization and drug-device integration. Conclusions Friction, as a unique endogenous/exogenous stimulus, enables highly precise drug delivery. Advancing clinical translation requires establishing biotribological quantitative models, developing responsive biomimetic materials, and promoting integrated ‘drug‑device’ development through multidisciplinary collaboration.