Search Results (130)

Phytochemicals have attracted considerable attention as therapeutically relevant bioactive compounds due to their diverse pharmacological activities, including anti-inflammatory, antioxidant, anticancer, and metabolic regulatory effects. However, their clinical translation is frequently hindered by unfavorable pharmaceutical properties such as poor aqueous solubility, chemical instability, rapid metabolism, and limited bioavailability. These challenges have constrained the reproducibility and therapeutic reliability of phytochemical-based interventions. In this context, nanotechnology-enabled delivery systems have emerged as effective strategies to overcome the intrinsic limitations of phytochemicals and enhance their biological performance. This review provides a comprehensive overview of recent advances in nanotechnology-based delivery platforms for phytochemicals, with emphasis on lipid-based nanocarriers, polymeric nanoparticles, nanoemulsions and self-nanoemulsifying drug delivery systems, inorganic and hybrid nanocarriers, as well as hydrogel-based and transdermal delivery systems. We discuss how rational nanocarrier design improves solubility, stability, pharmacokinetics, cellular uptake, and tissue targeting, thereby enhancing therapeutic efficacy across multiple disease areas. In addition, critical safety, toxicity, manufacturing, and regulatory considerations that influence translational potential are addressed. By adopting a delivery-centered perspective, this review highlights current challenges and future opportunities in nano-phytomedicine and underscores the importance of integrating nanotechnology, biological insight, and regulatory-conscious development to advance phytochemicals toward clinically viable therapeutic applications. Full article

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE), characterized by immune system disorders and multiple organ damage. Current clinical treatment of LN requires a complex multi-drug combination, which is often associated with severe side effects and low patient compliance. The aim of this study was to design a self-nanoemulsifying drug delivery system (SNEDDS) co-loading total glucosides of Paeonia (TGP) and dihydroartemisinin (DHA) to increase the solubility of the drug as well as achieve synergistic anti-inflammatory and immunomodulatory effects for LN therapy. Network pharmacology, molecular docking and molecular dynamics simulations were employed to predict the core therapeutic targets and related signaling pathways. The SNEDDS co-loaded with TGP and DHA was optimized via central composite design response surface methodology (CCD-RSM). Its physicochemical properties, particle size and the polydispersity index (PDI) of the optimized formulation were characterized. In vivo therapeutic efficacy was evaluated in MRL/lpr mice by measuring disease-related indicators (urinary protein, serum ANA, and anti-ds-DNA) and inflammatory cytokines (TNF-α, IL-6, and IL-1β). Renal tissue pathology was also examined. All data were analyzed by one-way analysis of variance (ANOVA) with p < 0.05 considered statistically significant. The core therapeutic targets predicted with high relevance were AKT1, MAPK1, MAPK3, and RELA. The optimized SNEDDS achieved a high loading capacity of 16.11 ± 0.43 mg/g for TGP and 12.79 ± 1.33 mg/g for DHA, with a particle size of (25.84 ± 0.30) nm and PDI of (0.07 ± 0.02). In MRL/lpr mice, SNEDDS treatment significantly reduced urinary protein levels (p < 0.01), serum ANA (p < 0.01) and anti-ds-DNA titers (p < 0.01) compared with the model group. Additionally, the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) were markedly decreased (p < 0.05), and renal tissue damage was alleviated. Conclusions: The SNEDDS co-loaded TGP and DHA is a promising oral nanotherapeutic strategy for LN, offering synergistic anti-inflammatory and immunomodulatory effects. Full article

Background/Objectives: The ABCG2 transporter actively effluxes anticancer drugs, reducing their efficacy and promoting multidrug resistance (MDR). Developing oral formulations of poorly soluble ABCG2 inhibitors remains challenging due to their low solubility and intestinal permeability. This study aimed to formulate and evaluate an ABCG2 inhibitor using micro- and nanoscale drug delivery systems. Methods: To address the poor solubility and bioavailability of the corresponding active ingredient, a self-nanoemulsifying drug delivery system (SNEDDS) was developed. The SNEDDS was encapsulated into microcapsules using sodium alginate crosslinked with calcium chloride. Five microcapsule formulations were developed, varying in the inclusion of polyvinylpyrrolidone (PVP), Transcutol^® HP and SNEDDS. The effects of the excipients on encapsulation efficiency, swelling capacity, enzymatic stability, dissolution, cytocompatibility, and permeability were systematically evaluated. Results: The SNEDDS exhibited monodisperse particle sizes and efficient drug entrapment. Results revealed that formulations incorporating PVP and SNEDDS improved encapsulation efficiency and bioavailability. SNEDDS-containing formulations demonstrated superior enzymatic stability in simulated gastric and intestinal fluids and provided the highest cumulative drug release in vitro. Cytotoxicity studies conducted on Caco-2 and MCF-7 cells demonstrated that our formulations were well tolerated, indicating favorable biocompatibility. Conclusions: Our findings demonstrate that SNEDDS-loaded alginate microcapsules offer an efficient platform for oral delivery of dimeric ABCG2 inhibitors, combining enhanced solubility, stability, and controlled release. The optimized formulation can be regarded as a promising strategy to enhance the oral bioavailability of efflux pump inhibitors and other poorly soluble drugs. Full article

Background/Objectives: Conventional solidification methods for liquid self-nanoemulsifying drug delivery systems face significant limitations. This includes complex manufacturing processes, high costs, and environmental concerns. This study aimed to develop and optimize a thermoresponsive self-nanoemulsifying drug delivery system (T-SNEDDS) for dapagliflozin as a sustainable alternative solidification technique. Methods: Oil and surfactant were selected based on solubility and emulsification studies. The Box–Behnken approach was used to examine the impacts of three independent variables (pluronic F127, propylene glycol, and dapagliflozin concentrations) on liquefying temperature and time. Optimized T-SNEDDS was characterized in terms of particle size, zeta potential, and dissolution performance. Stability assessment included centrifugation testing and a six-month storage evaluation. The green pharmaceutical performance was comparatively evaluated against five conventional solidification methods using ten adapted parameters. Results: Imwitor 308 and Cremophor EL were selected as optimal excipients for SNEDDS formulation. In addition, Pluronic F127 and propylene glycol were used to induce solidification during storage. The optimized formulation (8.60% w/w Pluronic F127, 10% w/w propylene glycol, and 5% w/w dapagliflozin) exhibited a liquefying temperature of 33.5 °C with a liquefying time of 100.3 s and a particle size of 96.64 nm. T-SNEDDS significantly enhanced dissolution efficiency of dapagliflozin (95.7%) compared to raw drug (42.4%) and marketed formulation (91.3%). Green pharmaceutical evaluation revealed that T-SNEDDS achieved the highest score compared to conventional approaches. Conclusions: T-SNEDDS represents a superior sustainable approach for SNEDDS solidification that offers enhancement in drug dissolution while addressing manufacturing, environmental, and economic challenges through its solvent-free and single-step preparation process with excellent scalability potential. Full article

Background/Objectives: Demyelination and neuroinflammation are central features of multiple sclerosis (MS), contributing to motor deficits and cognitive decline. Cuprizone (CPZ)-induced demyelination is a well-established model for studying multiple sclerosis-like neurotoxicity. This study investigated the neuroprotective and immunomodulatory effects of self-nanoemulsifying drug delivery systems (SNEDDSs) incorporating curcumin, piperine, and Zanthoxylum rhetsa seed oil. Methods: Male mice were divided into five groups: control, CPZ-only, and CPZ co-treated with three nanoformulations BFZ (blank SNEDDS), CFZ (curcumin-SNEDDS), and PFZ (curcumin–piperine SNEDDS). CPZ was administered for 5 weeks, followed by a 2-week recovery or treatment phase. Key neuroinflammatory markers like CD4, CD8, cholinergic (acetylcholinesterase, AChE), myelin integrity (MBP), BDNF, CREB, TNFα, Il-1β were assessed at weeks 5 and 7 using ELISA. Alterations in antioxidant enzymes, brain histology, and behavioral outcomes were also investigated. Results: At week 5, CPZ significantly increased CD4 and CD8 expression and reduced AChE and MBP levels, indicating neuroinflammation, cholinergic impairment, and demyelination. Nanoformulation treatments (both prophylactic and therapeutic) markedly reduced CD4 and CD8 levels, with PFZ showing the most pronounced effect. AChE activity was significantly restored in all treatment groups, with PFZ and CFZ exceeding baseline levels, suggesting enhanced cholinergic function. MBP levels were highest in PFZ-treated mice, surpassing control values and indicating strong remyelination potential. These improvements persisted and further advanced at week 7, especially in PFZ and CFZ groups. Conclusions: Curcumin-based SNEDDS, particularly PFZ, significantly mitigated CPZ-induced neuroinflammation, promoted remyelination, and restored cholinergic activity in the frontal cortex. These findings highlight the therapeutic potential of bioenhanced curcumin nanoformulations for treating demyelinating and neuroinflammatory disorders. Full article

Background: Onychomycosis responds poorly to topical therapy, and efinaconazole (EFN) has low aqueous solubility. Methods: This study aimed to develop a 10% w/w EFN self-nanoemulsifying system (SNEDDS) with improved solubility, permeation, antifungal activity, and stability. Excipients were screened by EFN saturation solubility. An MCT oil/Solutol HS 15/Labrafil M2125 CS SNEDDS (5/75/20, w/w) was optimized via a pseudo-ternary diagram. Characterization included droplet size, PDI, and zeta potential, morphology, and drug–excipient compatibility. Solubility was measured across pH. Permeation of EFN SNEDDS vs. EFN suspension was tested by Franz diffusion cells. Antifungal activity against Trichophyton rubrum and Trichophyton mentagrophytes was assessed by paper-disc diffusion, and hyphal damage on human nails was examined by SEM. Stability was studied for six months under room, accelerated, and stress conditions. Results: The optimized SNEDDS formed sub-50 nm droplets with low polydispersity and favourable zeta potential. Solubility was maintained across pH, and cumulative permeation increased 13.6-fold versus suspension. Paper-disc assays showed larger inhibition zones at lower EFN doses. SEM on human nails revealed marked hyphal destruction. TEM confirmed spherical nanoemulsion droplets. FT-IR showed no new peaks, supporting compatibility. Particle size, PDI, zeta potential, and drug content remained stable over six months under all storage conditions. Conclusions: A 10% w/w EFN SNEDDS enhanced solubility, transungual permeation, and antifungal efficacy while maintaining robust stability, supporting its potential as an ethanol-free therapy for onychomycosis. Full article

Background/Objectives: Holy basil (Ocimum tenuiflorum L.) essential oil exhibits antioxidant, antimicrobial, and anesthetic activities, mainly due to eugenol, methyl eugenol, and β-caryophyllene. However, its clinical application is limited by poor water solubility, instability, and low bioavailability. This study developed and compared two delivery systems, self-nanoemulsifying drug delivery systems (SNEDDS) and microemulsions (ME), to enhance their stability and fish anesthetic efficacy. Methods: The optimized SNEDDS (25% basil oil, 8.33% coconut oil, 54.76% Tween 80, 11.91% PEG 400) and ME (12% basil oil, 32% Tween 80, 4% sorbitol, 12% ethanol, 40% water) were characterized for droplet size, PDI, zeta potential, pH, and viscosity. Stability was evaluated by monitoring droplet size and PDI over time and by determining the retention of eugenol, methyl eugenol, and β-caryophyllene after storage at 45 °C. Fish anesthetic efficacy was tested in koi carp (Cyprinus carpio var. koi). Results: SNEDDS maintained a small droplet size (~22.78 ± 1.99 nm) and low PDI (0.188 ± 0.088 at day 60), while ME showed significant size enlargement (up to 177.10 ± 47.50 nm) and high PDI (>0.5). After 90 days at 45 °C, SNEDDS retained 94.45% eugenol, 94.08% methyl eugenol, and 88.55% β-caryophyllene, while ME preserved 104.76%, 103.53%, and 94.47%, respectively. In vivo testing showed that SNEDDS achieved faster anesthesia (114.70 ± 24.80 s at 120 ppm) and shorter recovery (379.60 ± 15.61 s) than ME (134.90 ± 4.70 s; 473.80 ± 16.94 s). Ethanol failed to induce anesthesia at 40 ppm and performed poorly compared to SNEDDS and ME at other concentrations (p < 0.0001). Conclusions: SNEDDS demonstrated superior physical stability and fish anesthetic performance compared to ME. These findings support SNEDDS as a promising formulation for delivering holy basil essential oil in biomedical and aquaculture applications. Full article

Background/Objectives: The major limitations of self-nanoemulsifying systems include complex processing and expensive instrumentation required for solidification approaches. In this study, smart poloxamer-based solidification strategies were used to develop and optimize febuxostat-loaded formulations. Methods: A self-nanoemulsifying drug delivery system (SNEDDS) component was selected based on solubility and emulsification tests. The influence of poloxamer molecular weight (low or high) and its concentration (2–10% w/w) on formulation performance was assessed through the design of experiments. Finally, in-vitro melting assessment and a comparative dissolution test were performed on the optimized SNEDDS formulation. Results: Imwitor 988 and Tween 20 were selected to prepare the formulations. Increasing the molecular weight and concentration of the poloxamer significantly increased the temperature and time required for the melting of the SNEDDS formulation. The optimized SNEDDS formulation comprised 3.98% w/w poloxamer 188, which melts at 36 °C within 111 s. In-vitro melting showed that the formulation completely converted to a liquid state upon exposure to body temperature. Finally, the optimized SNEDDS formulation exhibited superior dissolution efficiency (96.66 ± 0.28%) compared to raw febuxostat (72.09 ± 4.33%) and marketed tablets (82.23 ± 3.10%). Conclusions: The poloxamer-based approach successfully addressed the limitations associated with conventional solidification while maintaining superior dissolution performance. Therefore, it emerges as a promising alternative approach for enhancing the bioavailability of poorly water-soluble drugs. Full article

Background/Objectives: Leishmaniasis is a prevailing infectious disease transmitted via infected phlebotomine sandflies. The lack of an efficient vaccine with respect to immunogenic antigens and adjuvanted delivery systems impedes its control. Following the induction of immune responses in mice vaccinated with multi-epitope Leishmania peptides (LeishPts) encapsulated in doubly adjuvanted self-nanoemulsifying drug delivery systems (ST-SNEDDSs), this study aims to assess ST-SNEDDS-based nanoemulsions as vehicles for the delivery of antigenic proteins. Methods: Model antigens (e.g., BSA-FITC, OVA) were encapsulated in ST-SNEDDS after being complexed with the cationic phospholipid dimyristoyl phosphatidylglycerol (DMPG) via hydrophobic ion pairing. The nanoemulsions were characterized with respect to droplet diameter, zeta potential, stability, protein loading, protein release from the nanodroplets in different release media and cell uptake. Results: Both model antigens exhibited high encapsulation efficiency (>95%) and their release from the nanodroplets was shown to be strongly affected by the type of release medium (e.g., PBS, FBS 10% v/v) and the ratio of its volume to that of the oily phase, in agreement with predictions of protein release. Protein-loaded nanoemulsion droplets labeled with Cy-5 were found to be efficiently taken up by macrophages (J774A.1) in vitro. However, no colocalization of the labeled nanodroplets and BSA-FITC could be observed. Conclusions: It was revealed that in contrast with LeishPts, whole protein molecules may not be appropriate antigenic cargo for ST-SNEDDS formulations due to the rapid protein release from the nanodroplets in release media simulating in vitro culture and in vivo conditions such as FBS 10% v/v. Full article

Background/Objectives: The Self-Nanoemulsifying Drug Delivery System (SNEDDS) has been widely applied in oral drug delivery, particularly for poorly water-soluble compounds. The successful development of SNEDDS largely depends on the precise composition of its components. This narrative review provides an in-depth analysis of Quality by Design (QbD), Design of Experiment (DoE), and in silico approach applications in SNEDDS development. Methods: The review is based on publications from 2020 to 2025, sourced from reputable scientific databases (Pubmed, Science direct, Taylor and francis, and Scopus). Results: Quality by Design (QbD) is a systematic and scientific approach that enhances product quality while ensuring the robustness and reproducibility of SNEDDS, as outlined in the Quality Target Product Profile (QTPP). DoE was integrated into the QbD framework to systematically evaluate the effects of predefined factors, particularly Critical Material Attributes (CMAs) and Critical Process Parameters (CPP_S), on the desired responses (Critical Quality Attributes/CQA), ultimately leading to the identification of the optimal SNEDDS formulation. Various DoEs, including the mixture design, response surface methodology, and factorial design, have been widely applied to SNEDDS formulations. The experimental design facilitates the analysis of the relationship between CQA and CMA/CPP, enabling the identification of optimized formulations with enhanced biopharmaceutical, pharmacokinetic, and pharmacodynamic profiles. As an essential addition to this review, in silico approach emerges as a valuable tool in the development of SNEDDS, offering deep insights into self-assembly dynamics, molecular interactions, and emulsification behaviour. By integrating molecular simulations with machine learning, this approach enables rational and efficient optimization. Conclusions: The integration of QbD, DoE, and in silico approaches holds significant potential in the development of SNEDDS. These strategies enable a more efficient, rational, and predictive formulation process. Full article

Objectives: In this study, Quality by Design (QbD) was used to develop an optimized self-nanoemulsifying drug delivery system (SNEDDS) as an ophthalmic formulation of flurbiprofen (FLU). Using a Box–Behnken design (BBD), an optimal SNEDDS composition was crafted, targeting enhanced corneal permeability and increased bioavailability of the drug. Methods: The levels of each factor(X) were established using a pseudo-ternary diagram, and the Box-Behnken design (BBD) was used to evaluate the components of oil (18.9 mg), surfactant (70.7 mg), and co-surfactant (10.0 mg) to optimize the SNEDDS formulation. The response(Y) considered were particle size, polydispersity index (PDI), transmittance, and stability. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to analyze the particle size and morphology. In vitro and ex vivo diffusion tests were conducted to assess drug flux and permeability. Result: Using a response optimization tool, the values of each X factor were optimized to achieve a small particle size (nm), a low polydispersity index (PDI), and high transmittance (%), resulting in a formulation prepared with 18.9 mg of oil, 70.7 mg of surfactant, and 10.0 mg of co-surfactant. The optimized SNEDDS exhibited a small particle size of 24.89 nm, a minimal PDI of 0.068, and a high transmittance of 74.85%. A transmission electron microscopy (TEM) analysis confirmed the presence of uniform spherical nanoemulsion droplets with an observed mean diameter of less than 25 nm, corroborating the dynamic light scattering (DLS) measurements. Furthermore, the SNEDDS demonstrated improved stability under the stress conditions of heating–cooling cycles, with no phase separation, creaming, or caking observed and no differences in its particle size, PDI, or transmittance. In vitro and ex vivo diffusion tests demonstrated that the flux of the optimized SNEDDS (2.723 ± 0.133 mg/cm², 5.446 ± 0.390 μg/cm²) was about 2.5 and 4 times higher than that of the drug dispersion, and the initial diffusion was faster, which is suitable for the characteristics of eye drops. Conclusions: Therefore, the formulation of a flurbiprofen-loaded SNEDDS (FLU-SNE) was successfully optimized using the QbD approach. The optimized FLU-SNE exhibited excellent stability and enhanced permeability, suggesting its potential effectiveness in treating various ocular inflammations, including uveitis and cystoid macular edema. Full article

Croton cajucara Benth and Copaifera reticulata Ducke are prominent species in the traditional medicine of the Amazon region of Brazil. Copaifera species produce oil resin rich in bioactive diterpenes, and C. cajucara is a prolific producer of the diterpene 19-nor-clerodane trans-dehydrocrotonin (t-DCTN). This research aimed to develop a self-nanoemulsion drug delivery system (SNEDDS) by using copaiba oil resin (C. reticulata) as a carrier for t-DCTN. A stable SNEDDS single-phase nanoemulsion comprising Tween 80 (7%, w/w) and copaiba oil (0.5%, w/w) afforded a fine oil-in-water carrier system (SNEDDS-CO). The dropwise solubilization of t-DCTN (1 mg) into SNEDDS-CO resulted in the nanoformulation called SNEDDS-CO-DCTN. Transmission electron microscopy (TEM) analysis revealed spherical nanodevices, while particle size, polydispersity index (PDI), and zeta potential measurements indicated small nanodroplets (about 10 nm), uniformly distributed (between 0.1 and 0.2) and negatively charged for both systems. The in vitro kinetic of t-DCTN-loaded (SNEDDS-CO-DCTN) analyzed by using simulated conditions of the gastrointestinal microenvironment, as perspective for oral drug delivery, showed a controlled release profile, and corresponded to the Fickian diffusion model. The in vitro antioxidant activity of the samples (t-DCTN, SNEDDS-CO, and SNEDDS-CO-DCTN) was confirmed through total antioxidant capacity (TAC), reducing power, copper ion chelation, and hydroxyl radical scavenging assays. The antioxidant activity of SNEDDS-CO-DCTN which contained 1 mg of t-DCTN per mL⁻¹ of the carrier SNEDDS-CO was similar or even better when compared to the unload t-DCTN solubilized in DMSO (10 mg mL⁻¹). The SNEDDS formulations herein described were successfully obtained under moderated and controlled conditions, exhibiting effective physicochemical data and release characteristics with huge bioaccessibility for co-loading copaiba oil and t-DCTN. The novel colloidal system SNEDDS-CO-DCTN is a potential antioxidant nanoproduct and, from now on, is available for further pharmacological investigations. Full article

Objective: This study aimed to develop and characterize the physicochemical properties of a self-emulsion drug delivery system (SNEDDS) incorporating galangal extract (GE) and lemongrass oil (LGO). Then, to develop mouthwash powders containing GE- and LGO-loaded SNEDDS (GL-mouthwash powder) as a promising alternative for preventing and treating denture stomatitis. Methods: The solubility of GE in various vehicles was determined. Subsequently, pseudo-ternary phase diagrams of the different ingredients, oil (LGO), surfactant (Tween^® 80), and co-surfactant (Propylene glycol) were selected to develop the SNEDDS. Then, SNEDDS containing GE and LGO (GL-SNEDDS) were prepared and characterized. The optimized liquid GL-SNEDDS was transformed into GL-mouthwash powder by absorbing onto mannitol and blending with a sweetener. Subsequently, various evaluations including drug recovery, moisture content, emulsification time, stability, anti-Candida activity, and in vitro cytotoxicity were performed. Results: The developed SNEDDS formulation improved GE and LGO solubility. The optimized GL-SNEDDS exhibited a small droplet size of 148.2 ± 2.1 nm with a polydispersity index of 0.11 ± 0.03 and a zeta potential of 2.14 ± 0.11 mV. In addition, the GL-mouthwash powder demonstrated a high drug recovery of >80% with a low moisture of <10% and exhibited greater physicochemical stability under accelerated conditions. The developed GL-mouthwash powder rapidly formed a stable nanoemulsion within 2 min after reconstitution. Interestingly, GL-mouthwash powder exhibited strong anti-Candida activity with no toxicity to human fibroblast cells, which demonstrated superior biocompatibility relative to existing commercial products. Conclusions: These findings suggest that GL-mouthwash powder has potential as an alternative prevention and treatment of oral Candida infection. Full article

Background/Objectives: This study aims to develop a solid self-nanoemulsifying drug delivery system (SNEDDS) to enhance the solubility and oral bioavailability of cannabidiol (CBD). Methods: According to the solubility of CBD and pseudo-ternary phase diagrams of the different ingredients, an oil (medium-chain triglyceride, MCT), mixed surfactants (Labrasol, Tween 80), and a co-surfactant (Transcutol) were selected for the SNEDDS. CBD-loaded SNEDDS formulations were prepared and characterized. The optimal SNEDDS was converted into solid SNEDDS powders via solid carrier adsorption and spray drying techniques. Various evaluations including flowability, drug release, self-emulsifying capacity, X-ray diffraction (XRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), morphology, and pharmacokinetic characteristics were conducted. Subsequently, the solid powders with fillers, disintegrants, and lubricants were added to the capsules for accelerated stability testing. Results: The investigations showed that the two S-SNEDDS formulations improved the CBD’s solubility and in vitro drug release, with good storage stability. The pharmacokinetic data of Sprague Dawley rats indicated that a single oral dose of L-SNEDDS and spray drying SNEDDS led to a quicker absorption and a higher Cmax of CBD compared to the two oil-based controls (CBD-sesame oil (similar to Epidiolex^®) and CBD-MCT), which is favorable for the application of CBD products. Conclusions: SNEDDS is a prospective strategy for enhancing the solubility and oral bioavailability of CBD, and solid SNEDDS offers flexibility for developing more CBD-loaded solid formulations. Moreover, SNEDDS provides new concepts and methods for other poorly water-soluble drugs. Full article

Background: Sirtuin-1 (SIRT1), a histone deacetylase enzyme expressed in ocular tissues with intracellular localization, plays a critical protective role against various degenerative ocular diseases. The link between reduced SIRT1 levels and diabetic retinopathy (DR) has prompted the exploration of natural therapeutic compounds that act as SIRT1 agonists. Curcumin (CUR), which has been shown to upregulate SIRT1 expression, is one such promising compound. However, effective delivery of CUR to the deeper ocular tissues, particularly the retina, remains a challenge due to its poor solubility and limited ocular penetration following topical administration. Within this context, the development of self-nanoemulsifying drug delivery systems (SNEDDS) for CUR topical ocular delivery represents a novel approach. Methods: In accordance with our prior research, optimized SNEDDS loaded with CUR were developed and characterized post-reconstitution with simulated tear fluid (STF) at a 1:10 ratio, showing suitable physicochemical and technological parameters for ocular delivery. Results: An entrapment efficiency (EE%) of approximately 99% and an absence of drug precipitation were noticed upon resuspension with STF. CUR-SNEDDS resulted in a better stability and release profile than free CUR under simulated ocular conditions. In vitro analysis of mucoadhesive properties revealed that CUR-SNEDDS, modified with a cationic lipid, demonstrated enhanced interactions with mucin, indicating the potential for improved ocular retention. Cytotoxicity tests demonstrated that CUR-SNEDDS did not affect the viability of human corneal epithelial (HCE) cells up to concentrations of 3 μM and displayed superior antioxidant activity compared to free CUR in an oxidative stress model using retinal pigment epithelial (ARPE-19) cells exposed to hydroquinone (HQ). Cell uptake studies confirmed an enhanced accumulation of CUR within the retinal cells following exposure to CUR-SNEDDS compared to neat CUR. CUR-SNEDDS, at lower concentrations, were found to effectively induce SIRT1 expression. Conclusions: The cytocompatibility, antioxidant properties, and enhanced cellular uptake suggest that these developed systems hold promise as formulations for the delivery of CUR to the retina. Full article