With advances and widespread adoption of nanotechnology in the pharmaceutical field, natural product-based nanocarriers with drug-excipient homology have emerged as a major focus of current research. Natural products, including polysaccharides, proteins and lipids, are extensively used for the development of nanocarriers because of their abundant availability, excellent biocompatibility and notable pharmacological activities. These nanocarriers function as both drug carriers and therapeutic agents and are thus suitable for drug delivery. Furthermore, they can improve the physicochemical properties of drugs, increase the solubility of poorly soluble drugs, and enhance drug stability and pharmacological activity. Moreover, they can facilitate targeted drug delivery, thereby improving drug enrichment at specific sites. Such nanocarriers can exert intrinsic pharmacological effects and enhance the pharmacological effects of loaded drugs, thereby improving treatment effectiveness. Overall, this review highlights the combined and mutually beneficial advances in the integration of nanocarriers with natural products (e.g., polysaccharides, proteins and lipids) as well as the advantages of naturally occurring active small molecules based on drug-excipient homology.
Introduction: The application of Ganoderma lucidum spore oil (GLSO) is limited by its poor solubility, instability, and low bioavailability. Based on the “unification of medicines and excipients,” GLSO was used both as the oil phase and as an active ingredient to prepare a nanoemulsion (NE) to address the poor aqueous dispersibility and limited stability of GLSO. Methods: The GLSO NE was prepared using a low-energy method, and its composition was preliminarily screened using a pseudo-ternary phase diagram. The characterization and stability of the GLSO NE were evaluated. A comparative analysis of the immunomodulatory effects of GLSO and GLSO NE was performed in cyclophosphamide (CTX)-induced immunosuppressed ICR mice. Immune organ indices, blood cell counts, serum cytokine levels (IL-2, IL-4, IL-10), and histopathology of the spleen, thymus, and colon were assessed. Results: The GLSO NEs had an average particle size of 22.28 ± 0.50 nm (PDI: 0.343 ± 0.020) and a zeta potential of −11.60 ± 0.75 mV. The samples remained stable under different storage conditions. Compared to the Con group, the CTX group showed significantly lower immune organ indices and cytokine levels (IL‑2, IL‑4, IL‑10), as well as less histopathological damage. Both GLSO and GLSO NE treatments reversed these changes. Notably, the low‑dose GLSO NE (GLSON‑L) group showed significantly higher immune organ indices (P < 0.05) and cytokine levels (P < 0.05) compared with the low‑dose GLSO (GLSO‑L) group, and alleviated tissue damage more effectively. The high‑dose groups (GLSO‑H and GLSON‑H) both exhibited strong immunoenhancing effects, with no significant difference between them (P > 0.05). Discussion: These findings suggest that GLSON-L exerts immunostimulatory effects that can be leveraged to enhance CTX's therapeutic effects in mice. Furthermore, the results indicate that nanoencapsulation may enhance the therapeutic efficacy of GLSO by improving its solubility and stability. Conclusion: This study successfully developed a stable and effective GLSO NE, providing a promising strategy to improve the effectiveness and stability of GLSO for various applications, especially in the food and healthcare industries.
Background: This review explores the clinical role of botulinum toxin type A (BoNT-A) in treating Temporomandibular Disorders (TMDs) with a myofascial component, focusing on effectiveness, safety, injection protocols, and psychological and functional impact. Methods: Fourteen publications were retained for qualitative assessment after reviewing titles, summaries, and complete manuscripts. The risk of bias was appraised employing the ROBINS instrument. Results: BoNT-A treatment showed meaningful reductions in pain scores, especially in patients with high baseline pain or limited response to conservative care. Pain levels decreased significantly. Studies also reported improvements in jaw mobility, reduced muscle hyperactivity, and enhanced psychosomatic well-being. Some studies reported reductions in somatization and improvements in sleep quality. The depressive index remained unchanged, but functional disability improved significantly post-injection. Adverse effects, such as transient muscle soreness or facial changes, were rare and self-limiting. EMG data confirmed temporary neuromuscular relaxation lasting up to 22 weeks in some cases. Discussion: BoNT-A represents a valuable adjunctive or alternative therapy for myofascial TMDs, particularly in patients unresponsive to conventional treatments. It modulates pain perception and muscle overactivity via local and central mechanisms. However, variability in dosing, diagnostic criteria, and follow-up protocols underscores the need for standardized, well-designed clinical trials to optimize treatment strategies. Conclusion: BoNT-A is a valuable alternative for patients unresponsive to standard therapies. It helps reduce muscle overactivity and pain perception through local and central mechanisms. However, lack of standardized dosing, variable diagnostic frameworks, and inconsistent follow-up protocols highlight the need for further well-designed clinical trials to guide optimal use (ID: 1106625).
Background: Transcatheter arterial embolization (TAE) is a minimally invasive therapeutic strategy for treating hypervascular tumors, which relies on the intravascular delivery of embolic agents to obstruct blood supply. Embolic microspheres have emerged as promising agents due to their spherical shape and uniform size, which ensure predictable occlusion levels and targeted delivery. There is a pressing need for a controllable strategy to engineer multifunctional embolic microspheres. Methods: A novel droplet microfluidics-based method for the controllable fabrication of monodisperse alginate-chitosan composite (ACC) microspheres was developed. The mechanical and drugloading properties of the ACC microspheres were systematically characterized. The embolization performance of the optimized microspheres was visually evaluated in a microvascular chip model. Results: The microfluidic platform enabled the generation of highly monodisperse emulsion templates, leading to ACC microspheres with excellent size uniformity. Mechanical characterization revealed that the elasticity of the microspheres could be finely tuned, allowing for the production of highly elastic microspheres suitable for catheter injection. The ACC microspheres demonstrated favorable drug-loading capacity and sustained release characteristics. In the in vitro chip, the microspheres exhibited superior embolization performance. Discussion: The successful fabrication of monodisperse ACC microspheres underscores the precision of droplet microfluidics in creating complex biomaterial structures. The high elasticity is particularly critical for clinical embolization, as it prevents catheter clogging and ensures deep, uniform vessel occlusion. The demonstrated drug-loading capability positions these ACC microspheres as effective drug-eluting beads (DEBs) for combined embolization and local chemotherapy. The visual confirmation of effective embolization in the in vitro chip validates the functional performance of the microspheres. Conclusions: This study presents a robust microfluidic strategy for the controllable synthesis of monodisperse alginate-chitosan composite microspheres with tunable elasticity and favorable drugloading properties. The fabricated microspheres demonstrated excellent embolization performance in an in vitro model, validating their potential as advanced embolic agents. The findings offer valuable insights and a practical methodology for the rational design and preparation of next-generation multifunctional microspheres, which are highly desired for applications in embolization therapy.
Introduction: Liposomal drug delivery systems have evolved into clinically validated platforms across diverse therapeutic areas. This review aims to provide a translational perspective by linking fundamental formulation principles with clinically approved products and industrial manufacturing strategies. Methods: A structured narrative review was undertaken to examine liposomal formulations approved by major regulatory authorities across a range of clinical applications, including oncology, infectious diseases, vaccination, pain management, gene therapy, and regenerative medicine. The analysis focused on key formulation parameters, manufacturing techniques, and characterization methods. Relevant studies were identified through comprehensive searches of major scientific databases, including PubMed, Scopus, Web of Science, and ScienceDirect, as well as patent platforms such as Google Patents and Espacenet. Study selection was guided by predefined inclusion and exclusion criteria, prioritizing translational relevance, formulation strategies, manufacturing approaches, and clinically approved liposomal systems. Results: Lipid composition, vesicle size, surface functionalization, and release characteristics were identified as critical determinants of pharmacokinetics, therapeutic efficacy, and safety. Scalable and environmentally conscious manufacturing approaches, including supercritical fluid technologies, microfluidic systems, and solvent-reduction strategies, demonstrated strong alignment with regulatory and sustainability expectations. In characterization, emerging artificial intelligence-based tools showed potential for improved vesicle identification, size distribution analysis, and morphological assessment compared with conventional techniques such as dynamic light scattering and electron microscopy. Discussion: The integration of advanced formulation design, scalable manufacturing, and data-driven characterization enhances the translational potential of liposomal systems. However, challenges remain regarding standardization, regulatory acceptance of novel analytical tools, and reproducibility at industrial scale. Conclusion: Liposomal drug delivery systems represent a mature yet evolving platform. Bridging laboratory innovations with clinically and industrially viable solutions requires coordinated advances in formulation, manufacturing, and characterization. This review provides a practical framework for the development of next-generation liposomal systems with translational relevance.
Abstract: The treatment of inflammatory skin diseases poses significant challenges due to the complex Inflammatory Microenvironment (IME) and inherent limitations of the skin barrier. However, given its dynamic nature and pivotal involvement in disease pathogenesis, the IME represents an ideal target for precision intervention. By sensing real-time fluctuations in key biomarkers, including local pH, Reactive Oxygen Species (ROS) levels, inflammatory cytokines, and programmed cell death markers within the cutaneous microenvironment, Responsive Drug Delivery Systems (RDDS) enable intelligent and on-demand drug release. Consequently, RDDS confer superior therapeutic precision and efficacy while minimizing off-target adverse effects. This review systematically highlights the multifunctional capabilities of RDDS in modulating the IME. Key benefits encompass precise spatiotemporal drug release, targeted delivery, and combination therapy. Furthermore, these systems enable the safe administration of sensitive agents, enhance transdermal penetration, and facilitate theranostic integration. The article further summarizes recent advances and emerging trends in applying RDDS to diverse dermatological conditions, including psoriasis, melanoma, chronic wounds, atopic dermatitis, acne, and scleroderma. This review synthesizes the mechanisms and potential applications of RDDS, aiming to provide a theoretical foundation and inspire innovative designs for safer, more effective therapeutic strategies in dermatology.
Introduction: Transarterial chemoembolization (TACE) has become a crucial treatment method for hepatocellular carcinoma (HCC) in recent years. However, its effect is limited by low sensitivity to chemotherapy and unsatisfactory loading performance of the embolic agent. This study aimed to explore a promising treatment strategy that combines nanomedicine with a microcarrier to enhance the efficacy of TACE. Methods: In this work, the porous microcarrier was used to carry doxorubicin-loaded zeolitic imidazolate framework-8 nanoparticles (M@ZIF-8-DOX) according to a conventional drug loading method. The physical and chemical properties were characterized. An in vitro cell assay was used to assess the cytotoxicity and cellular uptake ability of the embolic agent. To evaluate the antitumor performance and safety, the M@ZIF-8-DOX was delivered by the standard interventional procedure in the rabbit VX2 liver tumor model Results: The M@ZIF-8-DOX effectively slowed the release of DOX in the bloodstream and extended the blood circulation time. In vitro studies revealed that ZIF-8-DOX showed high tumor cellular uptake and increased the intracellular DOX concentration. Furthermore, it was observed that M@ZIF-8-DOX could significantly inhibit tumor growth and proliferation while promoting tumor cell necrosis. Safety evaluation further confirmed that the M@ZIF-8-DOX had negligible toxicity to major organs and hepatorenal function Discussion: The structures of the nanoparticles can be disrupted by the acidic and hypoxic tumor microenvironment to release drugs in a short time. They usually increase intracellular drug concentrations to improve chemotherapy sensitivity and reduce systemic toxicity. Moreover, the combination of embolic agents and nanomedicine has demonstrated an excellent synergistic effect, providing a new strategy for TACE. Conclusion: The M@ZIF-8-DOX is a simple and highly effective embolic agent for TACE, and the concept of nano platform synergistically enhanced embolization therapy may be profound effect in the development of nanodrugs for HCC.
Diabetes mellitus-a disorder of glucose handling in the body-is appearing more frequently in clinic and registry alike. Public-health officials now label it as at once familiar and alarming. Among the clinical varieties, type 2 diabetes mellitus (T2DM) carries the heaviest demographic load and, perhaps not coincidentally, the bulk of research sponsorship. Most therapeutic playbooks still default to drugs that stall carbohydrate breakdown once the food reaches the intestines. At the end of that enzymatic assembly line sits the α-glucosidase molecule itself; without its action, oligosaccharides remain stranded, unprocessed. Pharmaceutical scientists have filed acarbose and miglitol under the same functional umbrella, though abdominal discomfort and spotty systemic absorption keep the prescriptions honest. The side effects have nudged inventors toward plant extracts, prodding them to browse the rainforest rather than the test-tube archive. One contender, α-mangostin from the queen-sized mangosteen fruit, nips at the enzyme but refuses to dissolve at anything resembling room temperature. Solid-dispersing it in polyvinylpyrrolidone (PVP) swaps the crystalline cage for a shapeless cloud and, by anecdotal report, boosts the apparent solubility tenfold or more. Laboratory batches usually employ flush-and-evaporate glassware, yet fluid-bed drying (FBD) is also in the mix when significance demands industrial scale. Both routes tweak the particle outline, and those subtle silhouettes end up steering bioavailability toward one wall or the other. To pin down the correlation, we decided to measure enzyme inhibition side-by-side with solubility gains from each processing strategy. Solubility experiments under controlled bulk conditions showed that solvent evaporation boosted reconcentration 2.1-fold and fluidized-bed drying raised it 1.8-fold. Enzyme inhibition tests, normalizing to final mass, revealed an IC50 value of 14.14±0.02 µg/mL. In parallel inhibition assays on -glucosidase, the plant extract outperformed commercial acarbose, recorded at 379.75±0.57 µg/mL, yet fell far short of pure quercetin, whose strength was 2.97±0.05 µg/mL. A side-by-side formulation comparison showed liquid-bed drying conserved inhibitory activity at 118.5964 g/mL, whereas the simpler evaporation method inflated that estimate to roughly 1,176.6459 g/mL. This research demonstrates that α-mangostin from the mangosteen fruit has the potential to be a stronger inhibitor of α-glucosidase enzyme than the commercial drug acarbose, although still less than the effectiveness of pure quercetin. The formulation process affects biological activity and solubility greatly. Solvent evaporation increases bioavailability more than fluid spray drying, yet diminishes enzyme inhibition effectiveness. On the other hand, fluidized bed drying retains enzyme inhibition activity much better, even though the increase in solubility is slightly lower. Thus, the formulation approach is the most important factor to consider in maximally utilizing the therapeutic potential of α-mangostin for development as natural antidiabetic drugs.
Introduction: Breast cancer remains a leading cause of mortality, with tumor immune evasion via the PD-1/PD-L1 axis limiting chemotherapy efficacy. To overcome this, we developed a cationic Nanostructured Lipid Carrier (NLC) system for the co-delivery of Paclitaxel (PTX) and PDL1- targeting siRNA. Methods: The P-NLC formulation was optimized using a Box-Behnken design and characterized via DLS, TEM, DSC, FTIR, and XRD. PD-L1 siRNA was complexed onto the cationic surface via electrostatic interactions, confirmed by gel retardation assays. Cellular uptake and cytotoxicity were evaluated in MCF-7 cells and a 3D spheroid model. Results: Complete siRNA binding was confirmed at a 100:1 mass ratio. The P-NLC-siRNA system exhibited sustained PTX release and enhanced cellular uptake in MCF-7 cells. In vitro assays demonstrated that the co-delivery system significantly suppressed cell viability compared to free PTX or PNLC alone, while the 3D model revealed improved apoptosis and tumor penetration. Discussion: These findings highlight the formulation's physicochemical stability and ability to enhance cytotoxicity. Although direct gene-silencing efficiency was not explicitly quantified in this study, the platform’s previously established in vivo PD-L1 knockdown capability supports the observed therapeutic potential. Conclusion: The developed cationic NLC enabled efficient co-loading of PTX and siRNA, demonstrating significant potential as a combined chemo-RNAi therapeutic strategy for improved breast cancer treatment.
Abstract: Exosome-based drug delivery systems have emerged as a transformative approach in cancer therapeutics, offering innovative solutions to overcome the limitations of conventional treatment modalities. Exosomes, nanoscale lipid bilayer vesicles naturally secreted by cells, exhibit unique properties such as intrinsic targeting capabilities, biocompatibility, and the ability to traverse biological barriers, making them ideal candidates for drug delivery. Their capacity to encapsulate diverse therapeutic payloads, including proteins, RNA, small molecules, and gene-editing tools, has catalyzed the development of novel cancer treatment strategies. This study highlights recent advancements in exosome engineering, including surface modification techniques to enhance targeting specificity, optimization of biogenesis pathways, and improvements in therapeutic cargo encapsulation. Key challenges, such as scalable production, delivery safety, and consistent drug loading, are addressed. By leveraging exosomes' natural properties, researchers are advancing precision oncology, enabling personalized, effective cancer therapies with reduced systemic toxicity. The ongoing progress underscores the translational potential of exosome-based platforms as next-generation therapeutic modalities, paving the way for more targeted, efficient, and patient-specific cancer treatments.
Introduction: One of the major complications in diabetic patients is foot disease. The microbial infections associated with this condition lead to skin infections, nail disease, and diabetic dermopathy. Nano-coating of textile fabric can be an approach to producing antimicrobial surfaces used as prophylactic agents to combat this foot disease. Method: Nystatin-loaded chitosan nanoparticles were impregnated onto cotton fabric. The nanoparticles were prepared using the ionic gelation method and coated onto the fabric. Results: Characterization showed a mean particle size of 154.6 nm and a zeta potential of +51.3 mV, indicating high stability. FTIR showed marked changes in peak positions, indicating interactions among chitosan, nystatin, and the fabric. SEM confirmed the presence of nanoparticles on the fabric, and XRD showed a change in the crystalline structure. The antifungal potential of the coated fabric was tested against C. albicans, with a ZOI of 23.5 mm before and 17.16 mm after washing cycles. Discussion: The coated fabric showed an initial burst release of nystatin followed by controlled diffusion, aligning with previous reports. Its antifungal activity remained stable after ten washing cycles, demonstrating superior durability compared to earlier fabric coatings. As this study was limited to in vitro evaluation, further in vivo validation is warranted. Conclusion: The coated fabric showed good antifungal activity with minimal loss of its inherent textile properties and preserved this effect after washing cycles. It can be used to make footwear for diabetic patients as a prophylactic measure.
Introduction/Objective: Rutin (R) and scopoletin (S) are natural flavonols, which have been shown to reduce heart disease, improve blood circulation, reduce inflammation, and even prevent diabetes. Certain physicochemical properties, such as poor solubility and poor oral bioavailability of RS, diminish their therapeutic effectiveness. This study aims to develop the RS niosomes formulation (RS-Ns-Opt) to improve the bioavailability and solubility of RS. Methods: Lipid-derived vesicles enclosing RS were developed by the thin-film hydration method, whereas surfactants and cholesterol formed the RS niosome. RS-Ns-Opt were developed and evaluated using the thin-film hydration method, drug release, DPPH assay, confocal laser scanning microscopy (CLSM), ex vivo nasal mucosa permeation, UV analysis, and differential scanning calorimetry (DSC). Results: Nanosize vesicles (55.22 nm) of RS-Ns-Opt were formed within an acceptable polydispersity index (PDI) (0.234). In contrast, the entrapment efficiency of R (72.64%) and S (72.44%) indicates efficient uniformity and automatic surface interaction. Moreover, RS-Ns-Opt exhibited notable drug release (79.96 ± 0.68%) and effective antioxidant activity (70.11 ± 3.07%) compared with RS suspension drug release (23.49 ± 2.11%) and antioxidant potential (75.59 ± 0.75%). Discussion: The CLSM study found that RS-Ns-Opt loaded with rhodamine B showed superior penetration compared to the control. Conclusion: The planned RS-Ns-Opt niosomes can improve the bioavailability of RS and are expected to gain wide consideration in the near future for healthcare applications.
Introduction: ICG suffers from poor photostability and rapid clearance in PTT. This study constructs an FA-modified, pH/NIR responsive COF nanodelivery system for targeted ICG delivery and precise controlled release. Methods: FA-Lip-IC was prepared by solvent evaporation. TEM and dynamic light scattering characterized morphology and size. Drug release was evaluated under different pH conditions with or without an 808 nm laser. Photothermal properties were assessed by an 808 nm laser. CLSM and flow cytometry analyzed FR-mediated cellular uptake. Biocompatibility was evaluated using an MTT assay, a hemolysis test, and a zebrafish model. Pharmacokinetics was monitored by blood fluorescence intensity in rats. Results: FA-Lip-IC showed uniform spherical morphology with a size of 577.4 ± 9.42 nm. The cumulative drug release reached 92.56 ± 0.81% at pH 5.5 with NIR irradiation. FA modification increased cellular uptake by ID8 and 4T1 cells. Under 808 nm laser irradiation, FA-Lip-IC induced a local temperature increase of > 20°C, with significantly higher cytotoxicity than free ICG. Hemolysis rate was < 3%, normal cell viability > 87%, zebrafish hatching rate > 90%, and blood circulation time was prolonged. Discussion: This platform integrates the high loading capacity of COFs with liposome biocompatibility. FA targeting and pH/NIR-responsive release enhance treatment precision. A limitation is the lack of in vivo efficacy data. Conclusion: FA-Lip-IC combines photothermal stability, active tumor targeting, and stimuliresponsive release, offering a promising strategy to overcome the limitations of conventional PTT and advance precision cancer therapy.
INTRODUCTION:Roxadustat, an inhibitor of hypoxia-inducible factor prolyl hydroxylase, has therapeutic potential for colitis but is limited clinically by poor water solubility and rapid gastrointestinal absorption. This study aimed to develop a pH-responsive, intestinal-targeted nanocarrier to enhance its oral bioavailability and anti-colitis efficacy. METHODS:Roxadustat-loaded liposomes (ROX-LP) were prepared via thin-film hydration with DSPG-PEG2000, cholesterol, and sodium cholate, then coated with Kollicoat MAE 100 P to form ROX-MAE@LP. The formulation was evaluated for physicochemical properties, in vitro release, cellular uptake, pharmacokinetics, and in vivo therapeutic efficacy. RESULTS:ROX-MAE@LP showed excellent encapsulation and uniform spherical morphology, with pH-dependent release (markedly increased at pH 6.8 and 7.4). Enhanced cellular uptake was observed in Caco-2 cells under intestinal pH-mimicking conditions. In rats, the oral bioavailability of ROX-LP (150.32±9.22%) and ROX-MAE@LP (255.36±12.82%) was improved compared with roxadustat suspension, and ROX-MAE@LP had a prolonged mean residence time (14.66±1.97 h). In a murine dextran sulfate sodium-induced colitis model, ROX-MAE@LP alleviated inflammation, downregulated pro-inflammatory cytokines, and promoted mucosal repair, outperforming ROX-LP and free roxadustat. DISCUSSION:The pH-responsive coating and intestinal-targeted property of ROX-MAE@LP effectively address the poor solubility and rapid absorption of roxadustat, enhancing local intestinal concentration and therapeutic effect in colitis, showing high potential for oral inflammatory bowel disease therapy. CONCLUSION:ROX-MAE@LP is an effective intestine-targeted delivery system that improves roxadustat's solubility, bioavailability and therapeutic outcomes in inflammatory bowel disease, while offering additional options for the development of novel roxadustat-based preparations and pHresponsive nanocarriers.
Introduction Objective: Combination therapy is considered an effective strategy to improve cancer treatment outcomes. This study aimed to develop a Pluronic F127-based nano-codelivery system (FDC) encapsulating docetaxel (DTX) and chlorin e6 (Ce6) to enhance the efficacy of PDT using Ce6 and the chemotherapy effect of docetaxel (DTX). METHODS:FDC was prepared by the thin film hydration method. Particle size, polydispersity index (PDI), zeta potential, drug loading efficiency, and 7‑day colloidal stability were characterized. Cellular uptake, reactive oxygen species (ROS) generation (using DCFH‑DA and SOSG probes), cytotoxicity (MTT assay), apoptosis (flow cytometry), and live/dead staining were evaluated in 4T1 breast cancer cells under light irradiation (630 nm, 29.8 mW/cm², 5 min). Statistical comparisons used Student's t‑test or one‑way ANOVA, with p < 0.05 considered significant. RESULTS:FDC exhibited a uniform hydrodynamic diameter of 200.33 ± 7.71 nm, a PDI of 0.392 ± 0.03, high drug loading efficiency, and good stability over 7 days. Compared with free Ce6, FDC significantly enhanced cellular uptake of Ce6 and markedly increased ROS generation upon light irradiation (p < 0.01). Cytotoxicity assays, apoptosis analysis, and live/dead staining also showed that FDC plus light induced the strongest anti-tumor effect, showing better antitumor effect than free Ce6, free DTX, and the physical mixture of Ce6+DTX Discussion: The improved anti-tumor effect of FDC may be related to enhanced cellular uptake of Ce6 and the co-delivery of DTX and Ce6. CONCLUSION:The FDC nano-co-delivery system represents a promising strategy for chemotherapy combined with photodynamic therapy against breast cancer.
Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) are lipid-based systems for drug delivery characterized by poor aqueous solubility and/or limited intestinal permeability, which are overcome by the spontaneous formation of nanosized oil-in-water emulsions upon exposure to gastrointestinal fluids. The progress of SNEDDS over the past years has led to higher levels of solid SNEDDS, supersaturable formulations, and multifunctional platforms incorporating bioenhancers to address both solubility- and permeability-limited absorption, particularly for Biopharmaceutics Classification System (BCS) Class III and IV drugs. This review critically summarizes and synthesizes key developments reported between 2020 and 2025, with emphasis on formulation strategies, mechanistic insights, biorelevant evaluation approaches, and translational considerations. Recent evidence also suggests that optimised SNEDDS may lead to improved drug solubilisation, modification of intestinal membrane permeability, inhibition of efflux transporters, and reduced presystemic metabolism, translating into improved and more consistent oral bioavailability. Preclinical and emerging clinical studies have shown increased systemic exposure, decreased pharmacokinetic variability, and, in some cases, further improved therapeutic outcomes across diverse drug classes. The significance of solidification technologies, digestion-aware formulation design, and quality-by-design frameworks as factors to enhance scalability and achieve reproducibility has also emerged from the review. Nevertheless, despite such great progress, there are still challenges, such as physiological variability in gastrointestinal conditions, surfactant-related tolerability, stability during storage and digestion, regulatory considerations, and the requirement for robust in vitro and in vivo translational models to be established. Taken together, SNEDDS represent a flexible and evolving platform for oral delivery of challenging drug candidates, with continued innovation expected to support their broader clinical translation.
INTRODUCTION/OBJECTIVE:Timolol Maleate (TM) is primarily used to treat glaucoma by reducing intraocular pressure. However, its efficacy is limited by poor ocular bioavailability (<5%) and systemic side effects. This study aimed to develop and evaluate Low-Molecular-Weight Chitosan (LMWC)-based complexes in an eye formulation to sustain TM release and enhance its corneal permeability. METHODS:TM-LMWC Polyelectrolyte Complexes (PECs) were prepared by ionic interactions between TM and LMWC and characterized for particle size, polydispersity, surface charge, and physicochemical properties. TM Liquid Medicated Nanoparticle Formulations (LMFs) were prepared by the solvent diffusion method, and their dissolution behaviors, release kinetics in simulated tear fluid, and ex vivo permeation through sheep corneas were evaluated. RESULTS:The prepared TM nanoparticles showed a uniform particle size (185-258 nm) and a positive zeta potential exceeding +26 mV, with encapsulation efficiency ranging from 28 to 35%. The formation of a polycationic complex was confirmed by the thermal and structural analyses. The LMFs showed a reduced particle size (65-130 nm). Moreover, the TEM image of LMF 4 revealed a spherical nanoparticle with a smooth surface. Sustained drug release was observed over 24 hours and best fitted to the Korsmeyer-Peppas model, indicating a Fickian diffusion (n < 0.45). Ex vivo studies showed LMF1 increased flux (2.54 ± 0.04 μg cm-2 h-1) and permeation coefficient (0.00987 cm·h⁻¹), representing a 2.62-fold increase in TM permeation. DISCUSSION:Chitosan molecular weight influenced PEC particle size due to differences in polymer chain length and viscosity. A sustained release of TM from LMFs was observed as TM was entrapped within the chitosan matrix and had to diffuse through the polymer or be released by matrix erosion. The enhanced corneal permeability was attributed to the mucoadhesive properties of the nanoparticles and their interaction with the corneal epithelium. CONCLUSION:The TM-based nanoparticle formulation enhanced corneal permeation and sustained TM release, offering a promising approach to improve ocular bioavailability and therapeutic efficacy.
INTRODUCTION:Research has shown that herbal medicine-derived vesicles act as biological agents and drug carriers. This study explores how Salvia miltiorrhiza nanovesicles alleviate atherosclerosis by regulating myeloid cells and inflammation. METHODS:We prepared SDNVs using high-speed centrifugation and analyzed them with nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and live imaging. Atherosclerosis was studied in ApoE-/- mice using models with bone marrow-derived macrophages (BMDM) and monocyte-derived macrophages (MDM). Macrophages were classified with immunofluorescence staining, and cytokines and inflammatory factors were measured using qRT-PCR and ELISA. Flow cytometry identified bone marrow stem cells, progenitor cells, and blood cell types. RESULTS:SDNVs exhibited characteristics of plant extracellular vesicles and significantly lowered total cholesterol, triglycerides, and LDL levels in atherosclerotic mice. Immunofluorescence staining showed fewer pro-inflammatory (M1) macrophages and more anti-inflammatory (M2) macrophages in arterial plaques. qRT-PCR and ELISA revealed reduced levels of inflammatory markers in the aorta and serum. Flow cytometry showed decreased bone marrow hematopoietic stem cells (Lin- Sca-1+ cKit+), progenitor cells (MPP4), and monocytes and neutrophils in peripheral blood. SDNVs also inhibited M1 polarization and promoted M2 polarization in BMDMs. DISCUSSION:SDNVs exert potent anti-atherosclerotic effects through lipid regulation and immune modulation, thus advancing PDEV-based therapeutic strategies for atherosclerosis. Limitations involve the use of a single ApoE-/- mouse model and unclear underlying mechanisms of cellular SDNV uptake. CONCLUSION:SDNVs demonstrate immune-regulating and anti-inflammatory effects. They effectively enter the body and modulate bone marrow cell, blood cell production, macrophage behavior, and inflammation, thereby slowing the progression of atherosclerosis.
Skin cancer, one of the most common malignancies globally, continues to present major therapeutic hurdles such as limited drug penetration, high systemic toxicity, and tumor recurrence. Nanomedicine has emerged as a powerful approach to overcome these challenges by enabling targeted, localized, and controlled drug delivery. Within this framework, the integration of Artificial Intelligence (AI) is transforming the way smart carriers are designed and optimized, moving drug development from trial-and-error to predictive, data-driven strategies. AI algorithms, including machine learning and deep learning, can predict drug-nanocarrier interactions, optimize particle size and surface chemistry for dermal penetration, and simulate release kinetics tailored to the tumor microenvironment. Intelligent nanocarriers developed with AI assistance also facilitate combination therapies such as chemo-, immuno-, and photodynamic therapy, offering synergistic benefits against resistant skin cancers. Furthermore, AI enables the personalization of treatment by analyzing patient-specific genomic and clinical data, guiding the creation of safer and more effective nanomedicine formulations. Despite these promising advancements, significant barriers remain in terms of data quality, model validation, and regulatory acceptance of AI-driven nanomedicine. Nonetheless, the convergence of AI and smart carrier technology represents a paradigm shift in precision oncology. This review uniquely emphasizes AI-guided nanocarrier design, optimization, and personalization specifically for skin cancer therapy, distinguishing it from broader AI-oncology reviews by focusing on smart drug-delivery systems rather than general diagnostic or predictive modeling applications.
