Search Results (312)

Background: Nanotechnology provides innovative strategies to enhance drug delivery and therapeutic efficacy through advanced nanocarrier systems. Objectives: This study aimed to develop and optimize a nanostructured lipid carrier (NLC) co-encapsulating curcumin (CUR) and resveratrol (RESV) using a fractional factorial design to develop a topical formulation with antioxidant and anti-inflammatory properties. Methods: NLCs were produced via hot emulsification followed by high-pressure homogenization, and their physicochemical characteristics, drug content, stability, release profile, antioxidant activity, skin delivery, and cellular compatibility were evaluated. Results: The optimized formulation exhibited an average particle size of approximately 300 nm, a polydispersity index below 0.3, and high drug loading for both compounds. Stability studies over 90 days revealed no significant changes in physicochemical parameters, confirming the formulation’s robustness. In vitro release assays demonstrated sustained release of both actives, with 58.6 ± 2.9% of CUR and 97 ± 3% of RESV released after 72 h. Antioxidant activity, assessed by the DPPH and ABTS assays, showed concentration-dependent radical-scavenging effects, indicating antioxidant potential. Skin permeation/retention experiments using porcine skin showed enhanced retention of CUR and RESV within the tissue, with no detectable permeation, indicating suitability for topical delivery. In addition, in vitro cell assays using human keratinocytes showed concentration-dependent responses and acceptable cellular compatibility. Conclusions: Overall, this study demonstrates the successful application of nanotechnology and experimental design to develop stable and efficient lipid-based nanocarriers containing natural polyphenol for topical therapy targeting oxidative and inflammatory skin disorders. Full article

Background: Diabetic nephropathy (DN) is largely driven by transforming growth factor-β1 (TGF-β1)-mediated fibrosis. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9) ribonucleoprotein (RNP) complexes offer precise gene disruption, yet effective non-viral delivery remains a challenge. This study developed cationic lipid-based hybrid nanostructured lipid carriers (NLCs) for intracellular delivery of TGFB1-targeting RNP as an early-stage platform for DN gene modulation. Methods: A single-guide RNA (sgRNA) targeting human TGFB1 was assembled with Cas9 protein (1:1 and 1:2 molar ratios). Hybrid NLCs comprising squalene, glyceryl trimyristate, and the cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) were formulated via optimized emulsification–sonication to achieve sub-100 nm particles. Physicochemical properties, including polydispersity index (PDI), were assessed via dynamic light scattering (DLS), while silencing efficacy in HEK293T cells was quantified using quantitative reverse transcription PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: Optimized NLCs achieved hydrodynamic diameters of 65–99 nm (PDI < 0.5) with successful RNP complexation. The 1:2 Cas9:sgRNA formulation produced the strongest gene-editing response, reducing TGFB1 mRNA by 67% (p < 0.01) compared with 39% for the 1:1 ratio. This translated to a significant reduction in TGF-β1 protein (p < 0.05) within 24 h. Conclusions: DOTAP-based hybrid NLCs enable efficient delivery of CRISPR–Cas9 RNP and achieve significant suppression of TGFB1 expression at both transcriptional and protein levels. These findings establish a promising non-viral platform for upstream modulation of profibrotic signaling in DN and support further evaluation in kidney-derived cells and in vivo renal models. Full article

Background/Objectives: Phytochemicals are known to be active contributors to a healthy life, providing valuable wound healing benefits. Methods: This research took an innovative approach that successfully overcame the bioavailability limits of herbal extracts, by entrapping CentellaA with HypericumP in nanostructured lipid carriers (NLCs) and hybrid hyaluronic acid (HA-NLCs) as valuable formulations with enhanced bioactivity. Results: NLCs and HA-NLCs showed excellent entrapping efficiency values for CentellaA and HypericumP ranging from 89.5 to 95.3%. Co-entrapping of CentellaA:HypericumP in a weight ratio of 4:1 and 2:1 led to diameters of 221.4 ± 2.08 nm for NLC-CentellaA-HypericumP and 220.3 ± 1.74 nm for hybrid HA-NLC-CentellaA-HypericumP. The bimodal calorimetric profile of NLCs contributed to a lower degree of lipid core structural organization. HA-NLC-CentellaA showed the safest biocompatibility behavior with BJ skin cells. Conclusions: The cells treated with NLC-CentellaA exhibited a favorable scratch wound closure and promoted the fastest BJ cell migration. NLC- and HA-NLC herbal extracts remodeled the cytoskeleton of BJ fibroblast cells. The morphological fluorescence changes revealed that the fibroblast cells retained intact their cytoskeleton, characteristic of a viable cell with no obvious stress. An active motility of cells treated with NLCs in the wound area was detected, indicating strong pro-migratory properties; e.g., for NLC-CentellaA, the wound was almost closed after 30 h. Designing NLCs with HA adaptability to reinforce the skin wound healing action represents a desired step for the development of herbal products that meets the challenge of combining the benefits of phytochemicals and nanotechnology to create value-added herbal products. Full article

Tyrosinase (EC 1.14.18.1) is the primary enzyme responsible for melanogenesis in mammals and enzymatic browning in food, creating a high demand for potent, safe inhibitors of this enzyme in the cosmetic, medical, and agricultural sectors. Conventional synthetic inhibitors often face limitations concerning their cytotoxicity and stability, necessitating the exploration of marine natural products (MNPs). Marine algae, comprising macroalgae (seaweeds) and microalgae (including cyanobacteria), represent an underexploited source of structurally diverse bioactives. Macroalgae, particularly brown species, yield complex phlorotannins, such as the non-competitive oligomer dieckol, which exhibits an IC50 of 2.16 µg/mL. Conversely, microalgae deliver high-potency, low-molecular-weight compounds, notably the synthesizable scytonemin monomer (ScyM) with an IC50 of 4.90 µM—significantly stronger than kojic acid. Mechanistic analysis, supported by molecular docking, reveals diverse modes of action, from the two-step slow binding of complex phlorotannins to the highly specific competitive binding of red algal bromophenols. Translational success requires the consistent application of green extraction techniques, such as Natural Deep Eutectic Solvents (NADESs), and advanced delivery systems, like Nanostructured Lipid Carriers (NLCs), to ensure the stability and bioavailability of these compounds for future cosmeceutical and medical applications. Full article

Sinomenine (SIN), as a potential therapeutic agent for rheumatoid arthritis (RA), exhibits advantages such as non-addictiveness. However, its low aqueous solubility and poor membrane permeability result in limited bioavailability, which compromises its therapeutic efficacy in conventional formulations. To address these limitations, this study developed nanostructured lipid carriers (NLCs) with optimized formulations and evaluated their pharmacodynamic performance. Molecular dynamics (MD) simulations were employed to screen excipients and analyze the blending system. SIN-loaded NLCs (SIN-NLCs) were prepared using high-pressure homogenization. Single-factor experiments were performed to optimize the processing conditions of SIN-NLCs. A three-factor, three-level experimental design was established using Design Expert 13 software and further refined through Box–Behnken design (BBD) response surface methodology. This approach enabled cross-validation between molecular dynamics simulations and conventional experiments. Additionally, transmission electron microscopy (TEM) was used to examine morphology, while X-ray diffraction analysis (XRD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR) were employed to characterize the physicochemical state of SIN in NLCs. Pharmacodynamic evaluation was performed in a RA model, supplemented by single-pass intestinal perfusion study (SPIP). Initially, MD simulations were employed to evaluate drug–excipient compatibility, thereby identifying suitable formulation excipients: stearic acid and oleic acid as lipid components, and Poloxamer 188 as the surfactant. Subsequently, single-factor experiments combined with the BBD response surface methodology were employed to optimize preparation parameters, establishing the ideal process conditions: drug-to-lipid ratio of 1:42, solid-to-liquid lipid ratio of 5.58:4.42, and Poloxamer 188 concentration of 1.20%. The optimized SIN-NLCs exhibited spherical particles with uniform dispersion and no agglomeration. The average particle size was 173.90 ± 1.97 nm, with a polydispersity index (PDI) of 0.18 ± 0.01, a zeta potential of −22.65 ± 0.60 mV, and an encapsulation efficiency (EE%) of 91.27% ± 0.01. Spectroscopic analysis confirmed that SIN existed in an amorphous state and was successfully encapsulated within the lipid matrix. In vivo, SIN-NLCs significantly reduced paw swelling and arthritis scores in model rats, promoted synovial cell proliferation, and suppressed inflammatory cell infiltration. The intestinal perfusion study demonstrated that SIN-NLCs were primarily absorbed in the small intestine and markedly enhanced drug permeability. SIN-NLCs represent an effective delivery system to enhance the solubility and permeability of SIN. This study provides a novel strategy and methodology for the formulation of hydrophobic drugs, offering valuable insights for future pharmaceutical development. Full article

Background/Objectives: Epalrestat (EPL), an aldose reductase inhibitor, exhibits poor aqueous solubility and limited ocular bioavailability, which significantly restricts its therapeutic efficacy in the treatment of diabetic retinopathy. To overcome these limitations, a novel nanostructured lipid carrier (NLCs)-laden contact lens system was developed to achieve sustained and enhanced ocular delivery of EPL. Methods: In this study EPL-loaded NLCs were prepared using Compritol^® 888 ATO (solid lipid), Labrafac™ WL 1349 (liquid lipid), and Solutol^® HS 15 (surfactant) using high-speed homogenization method. The formulations were statistically optimized using a D-optimal mixture design, considering globule size (Y₁), swelling index (Y₂), and drug release at 6 h (Y₃) as key responses. The optimized NLCs were incorporated into contact lenses via the soaking technique and evaluated for physicochemical properties, drug content, in vitro release, ex vivo corneal permeability, and in vivo ocular tolerance. Results: The optimized NLCs formulation showed a globule size of 41.85 ± 2.14 nm, zeta potential of −20.3 ± 1.8 mV, and entrapment efficiency of 93.32 ± 1.27%, indicating excellent physical stability with high drug encapsulation. The swelling index of the optimized NLCs-laden contact lens was 140.69 ± 4.32%, and the optical transmittance was 80.54 ± 1.12%, confirming adequate hydration and transparency for ocular use. The drug content was 96.32 ± 0.84%, ensuring uniform distribution throughout the hydrogel matrix. In vitro release studies demonstrated a sustained drug release of 98.12 ± 2.08% over 24 h, whereas ex vivo corneal permeation indicated significantly higher permeation (97.26 ± 1.95% at 6 h) compared with the control contact lens (38.14 ± 2.41% at 5 h). The in vivo Draize test confirmed that both blank and drug-loaded contact lenses were non-irritating and biocompatible. Conclusions: Thus, the optimized EPL NLCs-laden contact lens demonstrated enhanced corneal permeation, prolonged drug retention, and excellent ocular safety, offering a promising advancement in the management of diabetic retinopathy by improving bioavailability, reducing dosing frequency, and enhancing therapeutic efficacy. Full article

Background/Objectives: Curcumin (CUR), a natural polyphenol with poor solubility and significant first-pass metabolism, shows extremely low oral bioavailability. Although CUR-loaded nanostructured lipid carriers (CUR-NLCs) have demonstrated potential in enhancing oral absorption, direct evidence regarding their intestinal lymphatic transport mechanism remains insufficient, and current understanding largely relies on indirect speculation. Methods: CUR-NLCs were prepared by emulsion-ultrasonication and evaluated for their physicochemical properties including particle size, zeta potential, polydispersity index, encapsulation efficiency, drug loading, stability and release profile. A mesenteric lymph duct-jugular vein shunt rat model combined with transmission electron microscopy was employed to assess the pharmacokinetic behavior and lymphatic transport pathway. Results: CUR-NLCs had a mean size of 117.28 ± 1.32 nm, 99.99% encapsulation efficiency, and 1.73% drug loading. They exhibited good gastrointestinal stability and sustained release (<55% in 24 h). CUR-NLCs significantly enhanced oral absorption versus free CUR, with 5.13-fold higher relative bioavailability, 5.25-fold greater C_max, and extended half-life (33.49 ± 3.15 h). CUR was detected only in the lymph of the CUR-NLCs group, confirming intestinal lymphatic transport. TEM revealed abundant chylomicrons (0.1–2 μm) in jejunal epithelial cells, providing morphological support. Conclusions: This study directly demonstrates that CUR-NLCs improve oral bioavailability via intestinal lymphatic absorption, offering a viable strategy for delivering poorly soluble hydrophobic drugs. Full article

Background: Betulins (betulin, betulinic acid and lupeol) demonstrated antitumor and chemopreventive activity but showed low bioavailability due to their self-aggregation in hydrophilic environments. To overcome these disadvantages, their incorporation into lipid nanoformulations (PEGylated liposomes and Lipid Nanostructured Carriers (NLCs)) has proven to represent a viable solution. Objectives: The purpose of this study is to evaluate the size and incorporation rate of these molecules in nanoformulations, as well as their delivery and metabolic fate (pure betulinic acid versus a standardized extract, TT) relative to Doxorubicin using an in vivo protocol. The investigation extended our previous in vitro investigations towards an in vivo evaluation of antitumor activity, metabolic fate and toxicity in Wistar rats bearing Walker 256 carcinoma tumors over 21 days. Since previous studies used oral or intratumor administration, this exploratory study applied intravenous administration via microbubble-assisted sonoporation, considering its higher relevance for translational studies. Methods: The delivery and metabolic fate of the parent molecules, the identification of their fragments and metabolites using UHPLC-QTOF-ESI⁺MS were investigated, along with the identification of some toxicity biomarkers in rat plasma, tumor tissues and urine. Results: Preferential accumulation of Doxorubicin in tumors was observed compared to betulinic acid and TT components, as well as their persistence in plasma or elimination in urine. Compared to PEGylated liposomes, NLC formulations (especially NLC Doxo) induced a lower survival rate, a decreased bioavailability and increased toxicity by around 20%. Conclusions: These data are a starting point and complement the contrast-enhanced imaging and histology evaluations, which may contribute to the actual knowledge about the in vivo fate of betulins. Full article

UV radiation is responsible for acute and chronic adverse effects on the skin. In recent years, it has been shown that various phenolic acids, particularly cinnamic acid derivatives, prevent some of these effects. In the present study, the design and synthesis of three esters of ferulic acid, analogues of the octyl methoxycinnamate (OMC), one of the most commercially used filters, are presented. The esters were evaluated for their photoprotective activity against UVA and UVB radiation. The ester 3b exhibited an SPF of 9.22 and a λ_c value of 343.9, higher than the values of OMC (SPF value: 8.19, λ_c value: 337.7). The development and optimization of a novel encapsulation process of the synthesized esters in nanostructured lipid carriers (NLCs) and coating of the NLCs with chitosan was also performed. The optimization of the coating processes was performed using a Box–Behnken experimental design. The optimal nanosystems exhibited a size of 117.0 ± 5 nm, enhanced stability in dispersion, and 78% encapsulation efficiency. The nanoparticles were characterized by ATR/FT–IR, TGA, and TEM. Incorporation of the nanoparticle dispersions in a sunscreen formulation increased the SPF factor of the formulation up to 48%. The esters and nanosystems also showed a satisfactory ability to inhibit the peroxidation of linoleic acid (AAPH induced lipid peroxidation assay) (74–91% inhibition). Full article

Nano-carriers and dried gels were prepared to prevent the inherent flavor of Yuja (Citrus junos Tanaka) from rapidly deteriorating. The properties and stability of volatile components of Yuja dried gels were compared by using colloidal systems (nanoemulsion (NE) and nanostructured lipid carrier (NLC)), coating materials (maltodextrin (MD) and a mixture of MD and β-cyclodextrin (MD/βCD)), and drying processes (spray-drying and freeze-drying). Drying was found to have a significant effect on the particle size, moisture content, color, morphology, and volatile profiles of Yuja dried gels. Meanwhile, the stability of limonene and γ-terpinene, the main volatile components of Yuja oil, was affected by the colloidal system, coating material, and storage temperature. When Yuja oil was encapsulated by an NLC and MD/βCD coating, the degradation of limonene and γ-terpinene of Yuja dried gels was reduced during storage at 4 °C. Full article

Background: The management of triple-negative breast cancer (TNBC) remains a therapeutic challenge due to the presence of multidrug resistance (MDR) and hypoxia-induced chemoresistance, both of which substantially reduce the efficacy of conventional chemotherapy. Although certain natural compounds have shown the ability to modulate these resistance mechanisms, their clinical application is hindered by poor solubility and limited bioavailability. Among such phenolic compounds, 7-hydroxytyrosol (HTyr)—a phenolic compound from olive oil and olive leaves—has been reported to modulate hypoxia-inducible factor-1 (HIF-1). Methods: In this study, we developed hyaluronic acid (HA)-decorated solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for the targeted and synergistic co-delivery of paclitaxel (PTX) and hydroxytyrosol carboxylic acid esters (C_n-HTyrCA), precursors that share the antioxidant biphenolic moiety with HTyr. Results: Among the formulations tested, SLNs of trilaurin (TL) exhibited the highest entrapment efficiency (EE%), optimal average particle size, Zeta potential, and good colloidal stability. Of the synthesized C_n-HTyrCA derivatives, C₈- and C₁₀-HTyrCA showed superior loading capacity. In vitro release profiles indicated a sustained drug release pattern for both nanoparticles. HA decoration led to a marked increase in particle size and induced a shift in surface charge, confirming successful decoration and suggesting enhanced targeting potential via HA-CD44 interaction. Cytotoxicity assays conducted on MDA-MB-231 cells showed that PTX-loaded TL-SLNs exerted enhanced antitumor activity, particularly when HA-decorated, and a synergistic effect was observed upon co-administration with SLNs loaded with C₈-HTyrCA. Conclusions: Overall, our findings support the potential of SLN as a promising strategy to overcome key resistance mechanisms in TNBC, enabling reduced chemotherapeutic dosing and improving therapeutic outcomes. Full article

Objectives: This study was designed to optimize a ceftazidime (CTZ)-loaded nanocarrier that could efficiently permeate across corneal tissues. Moreover, N-acetylcysteine (NAC) was combined with an optimized CTZ-loaded formula to augment the antimicrobial activity and facilitate the efficient healing of Pseudomonas aeruginosa-induced keratitis. Methods: Different CTZ-loaded invasomes (INVs) and CTZ-loaded nanostructured lipid carriers (NLC) were fabricated and fully characterized via the determination of the entrapment efficiency (EE%), particle size (PS), surface charge, and percentage of CTZ release. Next, NAC was added to the optimized formulae from each nanocarrier, which were further assessed through ex vivo corneal permeation and in vitro antimicrobial activity studies. Finally, an in vivo evaluation of the optimal nanocarrier in the presence of NAC was performed. Results: Both nanocarriers showed nanoscale PS with sufficient surface charges. CTZ-loaded NLC formulae showed a higher EE% range with a sustained drug release profile. Both optimized formulae showed a spherical shape and excellent stability. Moreover, the antibacterial activity and biofilm inhibition assessments confirmed the synergistic effects of NAC when combined with different CTZ-loaded nanocarriers. However, the optimized CTZ-loaded INV formula achieved higher corneal permeation and deposition compared to the optimized CTZ-loaded NLC formula. Finally, the in vivo assessment confirmed the dominance of the optimized CTZ-loaded INV formula combined with NAC, where the microbiological, histopathological, and immunohistopathological examinations showed the rapid eradication of keratitis. Conclusions: Recent strategies for the incorporation of antibiotics into nanocarriers, combined with mucolytic agents, can offer a promising platform to boost the therapeutic efficiency of antibiotics and prevent antimicrobial resistance. Full article

Curcumin has good anti-cancer and antioxidant properties. However, the poor water solubility and low bioavailability limit its application in food products. This study constructed a nanostructured lipid carrier (Cur-CLA-NLC) encapsulating curcumin using conjugated linoleic acid (CLA) as the liquid lipid and stearic acid as the solid lipid. Cur-CLA-NLC exhibits significantly enhanced bioaccessibility, antioxidant activity, and cytocompatibility. CLA, as a liquid lipid in Cur-CLA-NLC, has a dual role as a structural stabilizer and bioactive agent, and synergistically enhances antioxidant activity with curcumin. In vitro simulated digestion studies showed that the bioaccessibility of curcumin in Cur-CLA-NLC (85.7%) was much higher than that in the pure curcumin (11.7%) and curcumin lipid mixtures (9.3%). In addition, the Cur-CLA-NLC system showed anti-lipid peroxidation ability and good biocompatibility. Therefore, CLA-NLC can serve as a potential delivery system for enhancing health benefits via functional foods. Full article

Lipid-based nanocarriers are ideal drug delivery systems for transdermal administration due to their biocompatibility and biodegradability. Their lipophilicity and/or similarity to the natural lipids of the epidermis enable intermolecular interactions with the lipid membrane and therefore result in effective passage through the skin. The purpose of this review is to focus on lipid-based drug delivery nanoplatforms administered via the transdermal route by summarizing the most recent developments with the intention of fast clinical translation. Liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), ethosomes, and transfersomes exhibit ideal physicochemical characteristics and encapsulation efficiency to enhance the effectiveness of the incorporated Active Pharmaceutical Ingredients (APIs). The state of the art for fabricating transcutaneous lipid drug delivery nanoparticles and the strategies for overcoming the current obstacles, as well as the added value of novel formulations, will be discussed within the scope of Quality by Design applications. The limitations and challenges that still exist will also be considered. Full article

Plant-derived compounds offer immense therapeutic potential, yet many suffer from limited solubility, instability, and poor bioavailability, restricting their clinical application. Curcumin, a polyphenol extracted from Curcuma longa, is one such molecule, with proven antioxidant and anti-inflammatory properties. To overcome its pharmacokinetic limitations, we developed Jamamina, a sustainable nanostructured lipid carrier (NLC) system incorporating curcumin and a Natural Deep Eutectic Solvent (NaDES) phase composed of malic acid and betaine. The bioinspired formulation, based on Amazonian tucumã butter and jambu oil, achieved high encapsulation efficiency (>80%) and curcumin amorphization, enhancing solubility and colloidal stability. In vitro assays with L132 demonstrated potent antioxidant activity (DPPH), a significant reduction in pro-inflammatory cytokines (TNF-α and IL-6), and upregulation of IL-10. The system also suppressed MMP-2/9 activity and preserved cytoskeletal integrity under oxidative stress. These findings highlight Jamamina as a multifunctional, eco-friendly nanoplatform that enables the pharmacological application of plant-derived curcumin, representing a promising platform for modulating redox balance and investigating inflammation in epithelial-like contexts. Full article