Search Results (300)

The advancement of efficient drug delivery systems continues to pose a significant problem in pharmaceutical sciences, especially for compounds with limited water solubility. Lipid-based systems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), have emerged as viable options owing to their biocompatibility, capability to safeguard labile chemicals, and potential for prolonged release. Nonetheless, the encapsulation efficiency (EE) and release dynamics of these carriers can be enhanced by including cyclodextrins (CDs)—cyclic oligosaccharides recognized for their ability to form inclusion complexes with hydrophobic compounds. This article offers an extensive analysis of CD-modified SLNs and NLCs as multifunctional drug delivery systems. The article analyses the fundamental principles of these systems, highlighting the pre-complexation of the drug with cyclodextrins before lipid incorporation, co-encapsulation techniques, and surface adsorption after formulation. Attention is concentrated on the physicochemical interactions between cyclodextrins and lipid matrices, which influence essential factors such as particle size, encapsulation efficiency, and colloidal stability. The review includes characterization techniques, such as particle size analysis, zeta potential measurement, drug release studies, and Fourier-transform infrared spectroscopy (FT-IR)/Nuclear Magnetic Resonance (NMR) analyses. The study highlights the application of these systems across many routes of administration, including oral, topical, and mucosal, illustrating their adaptability and potential for targeted delivery. The review outlines current formulation challenges, including stability issues, drug leakage, and scalability concerns, and proposes solutions through advanced approaches, such as stimuli-responsive release mechanisms and computer modeling for system optimization. The study emphasizes the importance of regulatory aspects and outlines future directions in the development of CD-lipid hybrid nanocarriers, showcasing its potential to revolutionize the delivery of poorly soluble drugs. Full article

This study presents a methodological framework for optimizing “blank” solid lipid nanoparticles (SLNs), focusing on the use of a design of experiments (DOE) approach. Rather than emphasizing the applications of SLNs, the objective is to identify and optimize critical formulation and process parameters—specifically those influencing particle size (PS), polydispersity index (PDI), and zeta potential (ZP)—during early development stages. A non-classical mixed design was applied using AZURAD^® software (version 4.4.1), incorporating a mixture variable for lipid composition (comprising carnauba wax, glyceryl behenate, glyceryl distearate), and two quantitative factors: the percentage of polysorbate 80 (P80) in the P80/sorbitan oleate surfactant system and ultrasound (US) treatment time. The DOE analysis identified P80 concentration as a key parameter, with optimal formulations observed when P80 ranged between 35% and 45%. A fixed P80 ratio of 41% and a US time of 7.5 min enabled precise adjustment of lipid composition. Following a desirability function analysis, an optimized formulation was obtained with a PS of 176.3 ± 2.78 nm, a PDI of 0.268 ± 0.022, and a ZP of −35.5 ± 0.36 mV. These findings validate the relevance of our DOE-based strategy, offering a scalable, cost-effective platform that reduces material use, time, and analytical effort in SLN development. Full article

Botrytis cinerea is one of the phytopathogenic fungi of the greatest economic importance worldwide. Essential oils (EOs) have been proposed as a sustainable alternative to reduce the growth of phytopathogenic fungi. Nevertheless, few studies exist about its mechanisms of action. This study evaluated the antifungal activity of EOs from Citrus reticulata, Citrus limon, Citrus sinensis, and Citrus paradisi peels and their encapsulation inside solid lipid nanoparticles (SLNs). Accordingly, Citrus EOs were mainly constituted by monoterpene hydrocarbons, where limonene was the most abundant in all EOs. C. reticulata and C. limon EOs reduced the mycelial growth at above 54% after 96 h. The other EOs did not significantly impact the phytopathogen. C. reticulata EO increased the hyphae damage by 40%, but the spore germination was reduced by only 8.34%. It also significantly increased the pH, the electrical conductivity, and the release of intracellular absorbing material and soluble proteins in B. cinerea cultures. Contrary, the esterase, mitochondrial, and succinate dehydrogenase activities decreased at above 50%. C. reticulata EO into SLN reduced the mycelial growth of B. cinerea by 90–97%. These results show that the EO of C. reticulata alters the physiological and metabolic activities of B. cinerea to reduce its growth. Full article

Objectives: This study characterised and evaluated the stability, solubility, and in vitro drug release of OA- and AA-loaded SLNs. Methods: The OA- and AA-SLNs were formulated using the emulsion solvent evaporation method and characterised based on particle size (PS), polydispersity index (PDI), zeta potential (ZP), and transmission electron microscopy (TEM). Solubility studies were conducted in PBS (pH 1.2 and 6.8) and dH₂O using HPLC, while in vitro drug release was assessed in simulated intestinal fluid (SIF) (pH 6.8). Results: The optimised OA-SLNs (1:1 drug-to-lipid ratio) showed PS, PDI, ZP, and EE% values of 312.9 ± 3.617 nm, 0.157 ± 0.014, −17.0 ± 0.513 mV, and 86.54 ± 1.818%, respectively. The optimised AA-SLNs (1:2 drug-to-lipid: ratio) had a PS of 115.5 ± 0.458 nm, PDI of 0.255 ± 0.007, ZP of −11.9 ± 0.321 mV, and EE% of 76.22 ± 0.436%. The SLNs remained stable for 60 days at 4 °C and room temperature (p < 0.05). The solubility study revealed that free OA and AA showed no measurable values in the three solvents. However, OA-SLNs showed the highest solubility in H₂O (16-fold) followed by PBS at pH 6.8 (10-fold) and pH 1.2 (10-fold). AA-SLNs significantly improved the solubility in PBS at pH 6.8 (88-fold), compared to dH₂O (6-fold) and PBS at pH 1.2 (26-fold). In vitro drug release studies showed that OA release from the SLNs was significantly increased within 300 min (p < 0.05) compared to the free drug. Similarly, AA release from the SLNs was significantly increased within 300 min (p < 0.05) compared to free AA. Conclusions: These results demonstrate that SLNs enhance OA and AA solubility and drug release, suggesting a promising strategy for improving oral bioavailability and therapeutic efficacy. Full article

Obesity and associated metabolic disorders pose significant health challenges. Fucoxanthin, a lipophilic compound, has shown promising anti-obesity potential, but its poor solubility and bioavailability limit therapeutic efficacy. The successful formulation of solid lipid nanoparticles (SLNs) amplified fucoxanthin’s efficacy in mitigating obesity and the associated metabolic dysregulation. High-fat diet (HFD)-induced obese mice were treated with free fucoxanthin, lyophilized SLNs (L-SLN), and dispersed SLNs (D-SLN) loaded with fucoxanthin. The intervention with D-SLN demonstrated the most significant reduction in body weight gain (29.94%) and fat mass gain (61.80%) compared to the HFD group (p < 0.05), alongside notable improvements in metabolic indicators including fasting blood glucose, liver enzymes, lipid profile, and inflammatory markers such as leptin and monocyte chemoattractant protein 1 (MCP-1) levels. Histopathological evaluation corroborated these findings, showing highly reduced hepatic lipid droplet accumulation and improved adipocyte and testicular morphology. This advancement paved the way for translating fucoxanthin into a clinically effective anti-obesity agent. Full article

Background/Objectives: Continuous manufacturing is gaining importance in the nanopharmaceutical field, offering improved process efficiency and product consistency. To fully leverage its potential, the integration of Process Analytical Technology (PAT) tools is essential for real-time quality control and robust process monitoring. Among the critical quality attributes (CQAs) of nanosystems, particle size plays a key role in ensuring product consistency and performance. However, real-time size monitoring remains challenging due to complex process dynamics and nanosystem heterogeneity. Methods: This study evaluates the applicability of conventional Dynamic Light Scattering (DLS) and spatially resolved DLS (SR-DLS) using the NanoFlowSizer (NFS) as PAT tools in a temperature-regulated top-down nano-production line. Various lipid-based nanosystems, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsions (NEs), were investigated. To ensure reliable implementation, key factors such as sample dilution, viscosity, focus position, measurement angle and temperature effects were systematically assessed for offline and at-line DLS using the Litesizer 500, as well as for offline, inline, and online SR-DLS using the NFS. Results: Offline screening confirmed that selecting the appropriate dilution medium and rate ensures measurement reliability. At-line methods provided an efficient alternative by enabling rapid final product control with minimal manual intervention. Inline and online monitoring further enhanced process efficiency by enabling real-time tracking of size, reducing waste, and allowing immediate process adjustments. Conclusions: This study demonstrates that integrating offline, at-line, in-line, and online DLS techniques allows for comprehensive product monitoring throughout the entire production line. This approach ensures a streamlined process, enables real-time adjustments, and facilitates reliable quality control after production and during storage. Full article

Background/Objectives: Diabetic mouth ulcers are a pathological condition of the oral mucosa leading to increases in susceptibility to infection and prolonged wound healing time. Still, there is a lack of natural formulations for treating this condition. Our principal objective was to formulate solid lipid nanoparticles (SLNs) that contained Althaea officinalis (marshmallow) (M.) extract with clove oil (CO.), subsequently integrated into a collagen sponge for enhancing stability, solubility, sustained release, antimicrobial efficacy, and healing power when targeting diabetic oral ulcers. Methods: A factorial design of 34 trials was established to evaluate the influence of lipid concentration (A), SAA concentration (B), lipid type (C), and SAA type (D). The optimized M-CO-SLNs was selected using Design Expert^®, the based Poly dispersibility index (Y2), zeta potential (MV) (Y3), and encapsulation efficiency (%) (Y4). The optimized SLNs were integrated into a collagen sponge matrix and tested for their antibacterial and antifungal efficacy against Pseudomonas aeruginosa, Escherichia coli, and Candida albicans, respectively. Moreover, they were tested for their wound healing power in a diabetic mouth ulcer model. Results: The optimized formula (Run 16: 5% lipid concentration, 4% SAA concentration, capric acid) demonstrated P.S (110 ± 0.76 nm), ZP (−24 ± 0.32 mV), PDI (0.18 ± 0.05), and EE% (90 ± 0.65%.). The optimized M-CO-SLNs formula was incorporated into a cross-linked collagen sponge and showed superior antimicrobial efficacy, an increased swelling ratio, and was effective in an in vivo oral ulcer study, as evidenced by ELISA biomarkers, gene expression analysis, and histological analysis. Conclusions: M-CO-SLNs embedded in collagen sponges is a promising therapeutic formula for clinical application against diabetic mouth ulcers. Full article

Lipid nanoparticles (LNs) have emerged as advanced lipid-based delivery systems, offering an effective approach for encapsulating and protecting lipid-soluble bioactive compounds, increasing their bioavailability. Solid Lipid Nanoparticles (SLNs) and Nanostructured Lipid Carriers (NLCs) are particularly promising for bioactive compound entrapment. However, to fully exploit their potential, it is crucial to carefully select the appropriate lipid matrices and emulsifiers. This review offers a comprehensive, up-to-date examination, considering studies published in the last 15 years, of the chemical, physical, and structural characteristics of lipids employed in LN production, focusing on the key components of the formulations: lipid matrices, emulsifiers, and bioactive compounds. In addition, it provides an in-depth analysis of production methods, drawing on insights from the latest scientific literature, and emphasizes the most important characterization techniques for LNs. Key parameters, including particle size (PS), zeta potential (ZP), crystallinity, thermal behavior, morphology, entrapment efficiency (EE), load capacity (LC), and physical stability, are discussed. Ultimately, this review aims to identify critical factors for the successful production of stable LNs that efficiently encapsulate and deliver bioactive compounds, highlighting their significant potential for applications in food systems. Full article

Objectives: This study aimed to develop hesperidin solid lipid nanoparticles (HESP-SLNs) to enhance their stability, solubility, and sustained release for wound healing; further enhancement was achieved through prepared nanostructured lipid carriers (HESP-NLCs) using Tea Tree Oil (TTO) to explore their synergistic efficacy. Methods: A factorial design of 2⁴ trials was established to evaluate the influence of lipid type (X1), lipid conc (%) (X2), surfactant type (X3), and sonication amplitude (%) (X4) of prepared HESP-SLNs on the particle size (nm) (Y1), polydispersibility index (Y2), zeta potential (Y3), and encapsulation efficiency (%) (Y4). The optimized HESP-SLNs formula was selected utilizing Design Expert^® software version 13, which was additionally enhanced by preparing TTO-loaded HESP-NLCs. In vitro release, Raman spectroscopy, and transmission electron microscopy were carried out for both lipid nanoparticles. Cytotoxicity, in vivo wound-healing assessments, and skin irritancy tests were performed to evaluate the performance of TTO-incorporated HESP-NLCs compared to HESP-SLNs. Results: The optimized formula demonstrated PS (280 ± 1.35 nm), ZP (−39.4 ± 0.92 mV), PDI (0.239 ± 0.012), and EE% (88.2 ± 2.09%). NLCs enhanced Q6% release, (95.14%) vs. (79.69%), for SLNs and showed superior antimicrobial efficacy. Both lipid nanoparticles exhibited spherical morphology and compatibility between HESP and excipients. NLCs achieved the highest wound closure percentage, supported by histological analysis and inflammatory biomarker outcomes. Cytotoxicity evaluation showed 87% cell viability compared to untreated HSF cells, and the skin irritancy test confirmed the safety of NLCs. Conclusions: TTO-loaded HESP-NLCs are promising candidates exhibiting superior wound-healing capabilities, making them a potential therapeutic option for cutaneous wound management. Full article

Background/Objectives. Psoriasis is a common chronic skin inflammatory disorder pathogenetically associated with genetic, environmental, and immunological factors. The hallmarks of psoriatic lesions include sustained inflammation related to alterations in the innate and adaptive immune response, uncontrolled keratinocyte proliferation, differentiation, and death, as well as dysregulated crosstalk between immune cells and keratinocytes. In search of novel therapeutic strategies based on the use of natural products and dietary components to combine to the available conventional and innovative therapeutics, we explored the anti-inflammatory, antioxidant, and immunomodulatory activities of Curcumin (CU)-based solid lipid nanoparticles (SLNs) carrying the omega-3 fatty acid linolenic acid (LNA) in an in vitro model of psoriasis that had been previously constructed and characterized by us. Methods. This in vitro model consists of differentiated in vitro THP-1 macrophages (Mφs) and NCTC-2544 keratinocytes exposed or not to conditioned medium (CM) from Mφs treated with the Toll-like receptor-7 ligand imiquimod (IMQ). Results. In Mφs, the treatment with CU-LNA-SLNs inhibited the IMQ-induced expression of proinflammatory cytokines (IL-23, IL-8, IL-6: 43%, 26.5% and 73.7% inhibition, respectively, vs IMQ-treated Mφs), as well as the hyperproliferative response (12.8% inhibition vs IMQ-treated Mφs) and the increase in cell death observed in keratinocytes treated with Mφ-derived CM (64.7% inhibition). Moreover, in the same conditions, CU-LNA-SLNs reverted to control levels of the increased keratinocyte expression of two markers of ferroptosis, a form of death recently involved in the pathogenesis of psoriasis (TFRC and MDA: 13.4% and 56.1% inhibition, respectively). Conclusions. These results suggest that CU-LNA-SLNs could inhibit psoriatic inflammation, as well as the hyperproliferation and death of keratinocytes in psoriatic lesions, and could be considered as a new possible therapeutic strategy for psoriasis to be further evaluated for the topic treatment of psoriatic skin in vivo. Full article

Currently, problems related to antibiotic resistance are shifting the focus of pharmaceutical research towards natural molecules with antibacterial properties. Among them, flavonoids represent promising molecules with strong antibacterial features; however, they have poor biopharmaceutical properties. In this study, we developed solid lipid nanoparticles (SLNs) loaded with the flavanone naringenin (NRG) to offer an option for treating bacterial infections. NRG-SLNs systems were prepared by a solvent emulsification/diffusion and ultrasonication method, using Compritol^® 888 ATO (COM) as the lipid. The optimal formulation was obtained using a 10% (w/w) theoretical amount of NRG (NRG₁₀-SLNs), exhibiting homogeneous sizes (approximately 50 nm and 0.15 polydispersity index), negative zeta potential (−30 mV), and excellent encapsulation parameters (an encapsulation efficiency percentage of 97.9% and a drug content of 4%). NRG₁₀-SLNs presented good physical stability over 4 weeks. A cumulative drug release of 55% in 24 h and the prolonged release of the remaining amount over 10 days was observed. In addition, µ-Raman spectroscopy, differential scanning calorimetry, thermogravimetric analysis, and X-ray diffraction measurements were carried out to characterize the drug–lipid interactions. Finally, the in vitro antibacterial and antibiofilm activities of NRG₁₀-SLNs were assayed and compared to free NRG. NRG₁₀-SLNs were bacteriostatic against Staphylococcus aureus, including the methicillin-resistant S. aureus (MRSA) and Escherichia coli strains. An improvement in the antibacterial activity of NRG-loaded SLNs compared to the free molecule was observed against S. aureus strains, probably due to the interaction of the surfactant-coated SLNs with the bacterial surface. A similar trend was observed for the biofilm inhibition. Full article

Background/Objectives: Oxidative stress significantly impacts skin health, contributing to conditions like aging, pigmentation, and inflammatory disorders. Curcumin, with its potent antioxidant properties, faces challenges of low solubility, stability, and bioavailability. This study aimed to encapsulate curcumin in three lipid nanocarriers—solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and nanoemulsions (NEs)—to enhance its stability, bioavailability, and antioxidant efficacy for potential therapeutic applications in oxidative-stress-related skin disorders. Methods: The lipid nanocarriers were characterized for size, polydispersity index, ζ-potential, and encapsulation efficiency. Stability tests under various conditions and antioxidant activity assays (DPPH and FRAP methods) were conducted. Cytotoxicity in human dermal fibroblasts was assessed using MTT assays, while the expression of key antioxidant genes was evaluated in human dermal fibroblasts under oxidative stress. Skin penetration studies were performed to analyze curcumin’s distribution across the stratum corneum layers. Results: All nanocarriers demonstrated high encapsulation efficiency and stability over 90 days. NLCs exhibited superior long-term stability and enhanced skin penetration, while NE formulations facilitated rapid antioxidant effects. Antioxidant assays confirmed that curcumin encapsulation preserved and enhanced its bioactivity, particularly in NLCs. Gene expression analysis revealed upregulation of key antioxidant markers (GPX1, GPX4, SOD1, KEAP1, and NRF2) with curcumin-loaded nanocarriers under oxidative and non-oxidative conditions. Cytotoxicity studies confirmed biocompatibility across all formulations. Conclusions: Lipid nanocarriers effectively enhance curcumin’s stability, antioxidant activity, and skin penetration, presenting a targeted strategy for managing oxidative stress in skin applications. Their versatility offers opportunities for tailored therapeutic formulations addressing specific skin conditions, from chronic disorders like psoriasis to acute stress responses such as sunburn. Full article

Objectives: Micelles, liposomes, and solid lipid nanoparticles (SLNs) are promising drug delivery vehicles; however, poor aqueous stability requires post-processing drying methods for maintaining long-term stability. The objective of this study was to compare the potential of lipid-based micelles, liposomes, and SLNs for producing stable re-dispersible spray-dried powders with trehalose or a combination of trehalose and L-leucine. This study provides novel insights into the implementation of spray drying as a technique to enhance long-term stability for these lipid-based nanocarriers. Methods: Aqueous dispersions of LDV-targeted micelles, liposomes, and SLNs loaded with paclitaxel (PTX) were converted into re-dispersible powders using spray drying. The physicochemical properties of the nanocarriers were determined via scanning electron microscopy (SEM), Karl Fischer titration, differential scanning calorimetry (DSC), and dynamic light scattering (DLS). Short-term stability of all nanocarrier formulations was compared by measuring particle size, polydispersity index (PDI), and paclitaxel retention over 7 days at room temperature and at 4 °C. Results: Paclitaxel-loaded micelles, liposomes, and SLN formulations were successfully converted into well-dispersed spray-dried powders with acceptable yields (71.5 to 83.5%), low moisture content (<2%), and high transition temperatures (95.1 to 100.8 °C). SEM images revealed differences in morphology, where nanocarriers spray-dried with trehalose or a combination of trehalose and L-leucine produced smooth or corrugated particle surfaces, respectively. Reconstituted spray-dried nanocarriers maintained their nanosize and paclitaxel content over 7 days at 4 °C. Conclusions: The results of this study demonstrate the potential for the development of spray-dried lipid-based nanocarriers for long-term stability. Full article

Background/Objectives: This study aims to evaluate the efficacy of curcumin (CUR), a natural polyphenol with potent antimicrobial and anti-inflammatory properties, when formulated as solid lipid nanoparticles (CUR-loaded SLN) against Enterococcus faecalis. Methods: Solid lipid nanoparticles (SLNs) were prepared as a carrier for CUR, which significantly improved its solubility. SLNs made with cetyl palmitate and Tween 80 were obtained via the hot ultrasonication method. The physicochemical properties of CUR-loaded SLNs were evaluated, including their size, stability, and release profile. Antimicrobial testing was conducted against both sessile and planktonic E. faecalis populations. Cytotoxicity was assessed on human gingival fibroblasts. Results: The CUR-loaded SLNs exhibited about 200 nm and a −25 mV surface potential, and the encapsulation of CUR did not affect the physicochemical properties of SLNs. CURs were released from SLNs in a controlled and sustained manner over 100 h. The nanoparticles remained stable for at least two months when stored at 4 °C or 25 °C, making them suitable for clinical use. Antioxidant activity was confirmed through DPPH and ABTS assays. Free CUR significantly reduced the planktonic E. faecalis CFU counts by approximately 65% after 24 h of exposure. However, this inhibitory effect diminished with longer exposure times (48 and 72 h). Antimicrobial activity studies of CUR-loaded SLNs showed dose- and time-dependent effects, in the 2.5–10 µg/mL range, against both sessile and planktonic E. faecalis populations, over 24 to 72 h. The CUR-loaded SLNs showed good cytocompatibility with human fibroblasts up to 2.5 μg/mL, suggesting low toxicity. Conclusions: CUR-loaded SLNs demonstrate significant antimicrobial activity against E. faecalis, along with good cytocompatibility, indicating their potential as an effective adjunct therapy in endodontic treatments. Full article

This study explores the development and characterization of lyophilized chondroitin sulfate (CHON)-loaded solid lipid nanoparticles (SLN) as an innovative platform for advanced drug delivery. Background/Objectives: Solid lipid nanoparticles are increasingly recognized for their biocompatibility, their ability to encapsulate diverse compounds, their capacity to enhance drug stability, their bioavailability, and their therapeutic efficacy. Methods: CHON, a naturally occurring glycosaminoglycan with anti-inflammatory and regenerative properties, was integrated into SLN formulations using the hot microemulsion technique. Two formulations (SLN-1 and SLN-2) were produced and optimized by evaluating critical physicochemical properties such as particle size, zeta potential, encapsulation efficiency (EE%), and stability. The lyophilization process, with the addition of various cryoprotectants, revealed trehalose to be the most effective agent in maintaining nanoparticle integrity and functional properties. Results: Morphological analyses using transmission electron microscopy (TEM) and atomic force microscopy (AFM) confirmed the dimensions of the nanoscales and their structural uniformity. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed minimal excipient interaction with CHON, ensuring formulation stability. Stability studies under different environmental conditions highlighted that SLN-2 is the most stable formulation, maintaining superior encapsulation efficiency (≥88%) and particle size consistency over time. Conclusions: These findings underscore the potential of CHON-loaded SLNs as promising candidates for targeted, sustained-release therapies in the treatment of inflammatory and degenerative diseases. Full article