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Aim: The present study aims to develop, optimize and assess hispolon (HPN) lipid nanocapsules (LNCs), solid lipid nanoparticles (SLNs) and suspension for treating hepatocellular carcinoma (HCC). Materials & methods: It included UPLC-MS/MS, solubility, optimization, characterization, stability, in vitro and in vivo studies. Results: HPN-loaded LNCs were developed using phase-inversion and temperature cycling, while SLNs and suspension using hot homogenization and trituration methods. HPN-LNCs had a particle size (PS) of 196.9 nm, a PDI of 0.315 and a zeta potential of -24.3 mV. HPN-S2 had a PS of 199.90 nm, a PDI of 0.381 and a zeta potential of -19.1 mV. HPN-SPN3 showed a PS of 946.60 nm, a PDI of 0.31 and a zeta potential of -0.1945 mV. Stability tests over 3 months and gastric stability testing in different media showed no significant changes in PS, PDI, entrapment efficiency (EE) and loading capacity (LC). HPN-LNCs demonstrated 96.22% sustained drug release over 25 h, outperforming HPN-S2 (87.12%) and HPN-SPN3 (22% within 2 h). HPN-loaded LNCs improved oral bioavailability by 2.03-times, the most effective hepatoprotective action and higher localization in liver tumors over HPN-S2 and HPN-SPN3. Conclusion: HPN-Loaded LNCs results are promising, but more safety data needed in the future. Article highlights HCC is the sixth most common tumor globally. Key risk factors include hepatitis B and C infections, which account for 60–85% of cases worldwide, and exposure to aflatoxin B1. CLSPN (Claspin), a protein essential for normal DNA replication, is regulated by ubiquitination. Studies have shown that CLSPN plays a significant role in HCC. Elevated levels of CLSPN have been observed in HepG2 and Huh7 cell lines, commonly used in liver cancer research. The elevated levels of CLSPN in these cell lines suggest its potential as a biomarker for HCC. Understanding its molecular mechanisms, particularly its role in the Wnt/β-catenin pathway, could lead to new therapeutic targets. Hispolon (HPN), a phenolic compound from PL, has anti-inflammatory, antiproliferative and antimetastatic effects but faces biopharmaceutical challenges such as low solubility and rapid metabolism. HPN-loaded LNCs are developed using phase-inversion and temperature cycling. Solid lipid nanoparticles are developed using hot homogenization and suspension is developed through trituration. Stability over 3 months and gastric stability testing in different media showed no significant changes in PS, PDI, EE and LC of HPN-loaded LNCs, HPN-S2 and HPN-SPN3. HPN-loaded LNCs improved oral bioavailability by 2.03-times. HPN-loaded LNCs showed the most effective hepatoprotective action and higher localization in the liver tumor compared with HPN-S2 and HPN-SPN3 suspension. HPN-loaded LNCs show promise for HCC treatment, but more in vivo safety data is needed soon. [ABSTRACT FROM AUTHOR]

Lipid nanoparticles such as nanoemulsions, nanostructured and solid lipid particles made of stearic acid and paraffin oil and stabilized with a mixture of nonionic surfactants Tween 60 and Span 60 are studied. The effect of incorporated yttrium stearate (YSt) as an additive in the modelling of radiopharmaceuticals and radiotherapy on the physicochemical properties of lipid nanoparticles is considered. The resultes indicate that the size of the oil droplets changes slightly when YSt is included in the nanoemulsions. The incorporation of YSt into lipid nanoparticles with stearic acid reduces their size, due apparently to the incorporation of YSt into the adsorption layer together with stearic acid. The studied lipid nanoparticles are resistant to radioactive irradiation with a dose of 5 kGy. No changes in the molecular structure of the components are observed after irradiation, and the aggregative stability of the lipid nanoparticles is not changed. [ABSTRACT FROM AUTHOR]

Introduction: Glioblastoma is a grade IV solid brain tumor and has a 15-month survival rate even after treatment. Glioblastoma development is heavily influenced by retinoblastoma protein (pRB) pathway changes. The blood–brain barrier, drug resistance, and severe toxicity of Temozolamide are key obstacles in treating glioblastoma. Innovative treatments targeting the pRB pathway with efficient delivery vehicles are required to treat glioblastoma. Methods: For this purpose, a library of 691 plant extracts previously tested in vitro for anti-cancerous, anti inflammatory, and anti-proliferative characteristics was created after thorough literature investigations. Compounds were docked against pRB pathway protein ligands using molecular operating environment and chimera. Their nuclear structure and drug-like properties were predicted through Lipinski rule and density functional theory analysis. Physio-chemical characterizations of naked and drug-encapsulated SLNPs assessed size, stability, entrapment efficiency, and drug release rate. Anti-cancer potential of drug and drug- loaded SLNPs was evaluated using U87, U251, and HEK cell lines. Formulations were tested for cancer cell metastatic potential using cell migration assays. Results: Silymarin (Sil) was identified as the most potent compound against CDK4, which was then encapsulated in stearic acid solid lipid nanoparticles (SLNP-Sil). Sil showed decreased cell viability 72 h after treatment against both U87 and U251 cell lines but had negligible cytotoxic effect on HEK-293. IC50 value of Sil was 155.14 µM for U87 and 195.93 µM for U251. Sil and SLNP-Sil effectively inhibited U87 and U251 cell migration 24 h after treatment. Discussion: Our results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit in vivo experimental verification using orthotropic xenograft mouse models against glioblastoma. [ABSTRACT FROM AUTHOR]

Co-delivery strategies have become an integral active delivery approach, although understanding of how the microstructural characteristics could be deployed to achieve independently regulated active co-delivery profiles, is still an area at its infancy. Herein, the capacity to provide such control was explored by utilizing Pickering emulsions stabilized by lipid particles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These dual functional species, regarding their concurrent Pickering stabilization and active carrying/delivery capabilities, were formulated with different solid lipid and surfactant types, and the effect on the release and co-release modulation of two hydrophobic actives separately encapsulated within the lipid particles themselves and within the emulsion droplets was investigated. Disparities between the release profiles from the particles in aqueous dispersions or at an emulsion interface, were related to the specific lipid matrix composition. Particles composed of lipids with higher oil phase compatibility of the emulsion droplets were shown to exert less control over their release regulation ability, as were particles in the presence of surfactant micelles in the continuous phase. Irrespective of their formulation characteristics, all particles provided a level of active release control from within the emulsion droplets, which was dependant on the permeability of the formed interfacial layer. Specifically, use of a bulkier particle surfactant or particle sintering at the droplet interface resulted in more sustained droplet release rates. Compared to sole release, the co-release performance remained unaffected by the co-existence of the two hydrophobic actives with the co-release behavior persisting over a storage period of 1 month. [ABSTRACT FROM AUTHOR]

The escalating global threat of antibiotic resistance underscores the urgent need for innovative antimicrobial strategies. This review explores the cutting-edge applications of nanotechnology in combating bacterial infections, addressing a critical healthcare challenge. We critically assess the antimicrobial properties and mechanisms of diverse nanoparticle systems, including liposomes, polymeric micelles, solid lipid nanoparticles, dendrimers, zinc oxide, silver, and gold nanoparticles, as well as nanoencapsulated essential oils. These nanomaterials offer distinct advantages, such as enhanced drug delivery, improved bioavailability, and efficacy against antibiotic-resistant strains. Recent advancements in nanoparticle synthesis, functionalization, and their synergistic interactions with conventional antibiotics are highlighted. The review emphasizes biocompatibility considerations, stressing the need for rigorous safety assessments in nanomaterial applications. By synthesizing current knowledge and identifying emerging trends, this review provides crucial insights for researchers and clinicians aiming to leverage nanotechnology for next-generation antimicrobial therapies. The integration of nanotechnology represents a promising frontier in combating infectious diseases, underscoring the timeliness and imperative of this comprehensive analysis. [ABSTRACT FROM AUTHOR]

Disruption in the wound-healing process is caused by the presence of bacteria and leads to major problems and delays in wound healing. The limitations of commonly used medicines for treating wound infections include drug toxicity, insufficient microbial coverage, poor penetration, and increased resistance. This study aimed to determine the effect of ciprofloxacin loaded in solid lipid nanoparticles (Cip-SLN) on Pseudomonas aeruginosa and ampiciliin-vancomycin loaded in solid lipid nanoparticles (Amp-Van-SLN) on Staphylococcus aureus in wounds. Antibiotics were encapsulated in SLNs using the double emulsion method and were characterized. The in-vitro effect of antibiotic-loaded nanoparticles on P. aeruginosa and S. aureus was assessed using well diffusion and MIC methods. Finally, the topical antibacterial activity of these nanoparticles against bacterial wound infection was measured in a mouse model. MIC results showed that in the first 24 hours, the free drug had a greater effect on inhibiting bacteria, and in 72 hours, the inhibitory effect of nanoparticles increased. There was no toxicity effect of 400 µg/mL of nanoparticles on cells. According to the findings, the groups treated with Cip-SLN and Amp-Van-SLN were more effective than the control group (untreated) in different concentrations. In the wound healing process, the group treated with solid lipid nanoparticles (SLNs) exhibited a greater epithelial thickness, indicating enhanced healing, compared to the group treated with the free drug. The use of SLN can increase the accumulation of antibiotics at the site of infection with a slow release of the drug due to its fatty nature, which leads to a significant inhibitory effect on bacteria and also improves wound healing. [ABSTRACT FROM AUTHOR]

Rifampicin (RF) is a potent antibiotic, but its clinical effectiveness is limited by poor water solubility and stability. To overcome these limitations, RF is encapsulated in solid‐lipid nanoparticles (SLNs) using a one‐pot microwave microemulsion method. This study aimed to synthesize and characterize RF‐loaded SLNs, evaluating their physicochemical characteristics and antimicrobial efficacy. The synthesized SLNs exhibit particle sizes ranging from 150 to 200 nm, with a high encapsulation efficiency of ≈55% and high loading capacity. The particles are imaged by cryogenic‐transmission electron microscopy and found to be circular and elongated, with RF homogenously distributed throughout the particles. The RF‐loaded SLNs demonstrate potent antimicrobial activity, as evidenced by disc diffusion assays. The SLNs exhibits a sustained drug release profile, highlighting their potential as an effective drug delivery system for antimicrobial treatment. These findings suggest that SLNs can enhance the stability, bioavailability, and therapeutic efficacy of hydrophobic drugs like RF. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats. Methods: We prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6 weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10–20 mg/kg), and diabetic + GAB-SLNs (10–20 mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41 nm), high negative Zeta potential (−32.18 ± 0.98 mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape. Results: GAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF). Conclusion: The preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders. [ABSTRACT FROM AUTHOR]

Acyclovir (ACY) is used to treat oral viral herpes but has low solubility and bioavailability. Stearic acid (SA) is lipophilic and can be combined with drugs. Therefore, this study aimed to characterize the properties of SA nanoparticles in increasing the cellular uptake of ACY by oral epithelial cells. The hypothesis was that SA nanoparticles increase sustained ACY release, are stable, and increase drug uptake. The production parameters (duration and amplitude of sonication) were optimized to produce solid lipid nanoparticles (SLN) of SA-containing ACY. Particle stability was characterized under different storage conditions (4 °C and 37 °C for 1, 15, and 45 days). SLN were further characterized for their pharmacokinetic profile, cytotoxicity, in vitro permeability, and ability to modulate gene expression and promote ACY uptake by oral epithelial cells. Pharmacokinetic studies revealed sustained and diffusional release of ACY from the SLN, with an initial burst release of 15 min. After 45 d of storage, SLN kept at both 4 °C and 37 °C showed a maximum release of > 90 % of the drug at 120 min. Cells treated with SLN presented a significantly higher intracellular drug content than those treated with ACY and significantly increased the genetic expression of TJP-1 , OCLN , and ECAD. The hypothesis was accepted as SA nanoparticles containing ACY can sustain drug delivery and enhance its absorption into epithelial cells. Therefore, SA nanoparticles are promising for improving ACY uptake in treating oral herpes and other infections caused by HSV-1. [ABSTRACT FROM AUTHOR]

Background: The fabrication of anti-Toxoplasma drugs with less side effects and desirable efficacy is one of the important research goals facing with toxoplasmosis. This study aimed to determine the anti-Toxoplasma effects of Cinnamon zeylanicum (CZ), Moringa oleifera (MO) oil encapsulated into solid lipid nanoparticles (SLNs). Methods: Vero cells were cultured with serial concentrations (1 mg/mL to 100 µg/mL) of CZ-SLNs and MO-SLNs in DMEM culture medium. The morphological, physical, and chemical features of nanoparticles were calculated. The cell viability assays and anti-T. gondii effects of CZ-SLNs and MO-SLNs were evaluated. The CC50 and IC50 indices of SLNs-enveloped extracts were calculated. Results: The particle sizes of MO-SLNs and CZ-SLNs were 411.5 and 365 nm, while PDI indices were 0.53 and 0.7, respectively. Transmission electron microscopy (TEM) showed that both MO-SLNs and CZ-SLNs were smoothed spherical nanoparticles with rounded edges. The cytotoxicity assay showed the CC50 value of MO-SLNs at concentrations of ˃10 mg/mL. In addition, 60% of T. gondii-infected Vero cells remained alive at the concentrations ≤ 1 mg/ml, while the MO-SLNs killed at least 90% of T. gondii tachyzoites with an IC50 > 1 µg/ml. The cytotoxicity of CZ-SLNs extract showed the CC50 at the concentration 0.1 mg/mL. More than 50% of Vero cells, infected with T. gondii tachyzoites, survived at a concentration less than 0.1 mg/mL (IC50 ˂ 0.1 mg/mL), while the CZ-SLNs killed at least 85% of T. gondii tachyzoites in all concentrations. Conclusion: The current results represented that the use of SLNs as a nano-carrier for M. oleifera and C. zeylanicum could kill T. gondii tachyzoites with low cytotoxicity, suggesting the effectiveness of these nano-emulsions along with the chemical agents in the treatment of Toxoplasma. [ABSTRACT FROM AUTHOR]

The objective of this study was to design and subsequently validate a precise and distinctive reversed-phase high-performance liquid chromatography (RP-HPLC) method for the accurate measurement of resveratrol (RSV), a polyphenol compound in the nanoformulations loaded into a microneedles (MNs) patch. The method was developed, optimized, and validated following International Council for Harmonisation guidelines (ICH) Q2 (R1), utilizing a reverse phase C18 column and a straightforward mobile phase. Samples were analyzed at ambient temperature, employing a flow rate of 1 mL/min and detecting wavelengths at 306 nm. The optimized HPLC method showcased remarkable linearity, selectivity, and precision. Specifically, it displayed exceptional linearity (R2 = 1.0) within a range of 4–20 μg/mL, with corresponding limits of detection (LOD) and quantification (LOQ) at 0.014 and 0.043 μg/mL, respectively. The methodology showed robustness with satisfactory intra- and interday precision. The developed stability-indicating HPLC method was applied to analyze RSV content and assess its loading in nanoformulations, and was proven to be selective, accurate, sensitive, reliable and consistent with regulatory guidelines. The RP-HPLC approach proved successful in assessing the drug content of RSV in novel formulations. [ABSTRACT FROM AUTHOR]

The use of lipid nanocarriers as components of cosmetic formulations may provide an opportunity to fully exploit the beneficial properties of pentapeptide-18 and retinol while reducing the undesirable effects that occur during retinoid therapy. This study aimed to evaluate the effectiveness of semi-solid formulations enriched with retinol and oligopeptide-loaded lipid nanocarriers. Solid lipid nanoparticles were produced using a high-shear homogenization method. The work included physicochemical characterization of the cosmetic products, and evaluation of their stability as well as their efficacy. The resulting semi-solid preparations were determined to be stable regardless of their storage temperature. No effect of the presence of lipid nanoparticles on the shelf-life stability of the cosmetic products was observed. A temperature of 25 °C was considered the recommended storage temperature for the tested semi-solid formulations. Beneficial effects of the cosmetic products were proven (in vivo study on volunteers), i.e., a significant reduction in the level of sebum secretion (anti-acne therapy) and a decrease in the number of facial wrinkles (anti-aging therapy). In addition, the protective properties of the lipid nanoparticles themselves against the skin were confirmed, reducing the irritating effect of retinol that is usually the case with classic retinoid therapies. [ABSTRACT FROM AUTHOR]

Natural bioactives are mixtures of compounds extracted from plants with physicochemical properties that are usually not favorable for penetrating the skin's complex barrier. Nanoparticles have important advantages both in dermatology and cosmetology: improved solubility and stability of encapsulated phytocompounds, controlled and sustained skin delivery, and enhanced skin permeation, leading to an improved bioavailability. This review focuses on two generations of lipid-based nanoparticles: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). An extensive overview on the recent studies on SLNs and NLCs entrapping essential oils, oils, herbal extracts, and phytocompounds for topical applications is presented, emphasizing their composition, physicochemical characterization, efficacy, and methodologies used to evaluate them. This review also summarizes topical systems containing natural bioactives incorporated into SLNs and NLCs, commercially available products and registered patents in the field. SLNs and NLCs turn out to be effective nanocarriers for skin applications, offering significantly improved encapsulation efficiency, stability, and bioactives delivery. However, their full potential is underexplored. Future applications should study the encapsulation potential of new natural bioactives and show more specialized solutions that address specific requirements; an improved product performance and a pleasant sensory profile could lead to increased customer compliance with the product use. [ABSTRACT FROM AUTHOR]

Within the field of nanomedicine, which is revolutionizing cancer treatment, solid lipid nanoparticles (SLNs) have shown advantages over conventional chemotherapy when tested on cancer cells in preclinical studies. SLNs have proven to be an innovative strategy for the treatment of triple-negative breast cancer cells, providing greater efficiency than existing treatments in various studies. The encapsulation of antineoplastic drugs in SLNs has facilitated a sustained, controlled, and targeted release, which enhances therapeutic efficiency and reduces adverse effects. Moreover, the surface of SLNs can be modified to increase efficiency. For instance, the coating of these particles with polyethylene glycol (PEG) decreases their opsonization, resulting in a longer life in the circulatory system. The creation of positively charged cationic SLNs (cSLNs), achieved by the utilization of surfactants or ionic lipids with positively charged structural groups, increases their affinity for cell membranes and plasma proteins. Hyaluronic acid has been added to SLNs so that the distinct pH of tumor cells would stimulate the release of the drug and/or genetic material. The current review summarizes the recent research on SLNs, focusing on the encapsulation and transport of therapeutic agents with a cytotoxic effect on triple-negative breast cancer. [ABSTRACT FROM AUTHOR]

Herein, we reported novel docetaxel-decorated solid lipid nanoparticle (DCT-SLN)-loaded dual thermoreversible system (DCT-DRTS) for intramuscular administration with reduced burst effect, sustained release and improved antitumor efficacy. The optimized DCT-DRTs was subjected to in-vitro and in-vivo analyses. Antitumor evaluation of the DCT-DRTS was executed and compared with DCT-hydrogel, and DCT-suspension trailed by the histopathological and immune-histochemical analyses. The DCT-SLN gave a mean particle size of 157 nm and entrapment efficiency of 93 %. It was a solid at room temperature, and changed to liquid at physiological temperature due to its melting point of about 32 °C. Unlikely, poloxamer mixture remained liquefied at 25-27 °C, however converted to gel at physiological temperature. This behavior demonstrated opposed reversible property of the DCT-SLN and poloxamer hydrogel in DCT-DRTS system, making it ideal for intramuscular administration and quick gelation inside the body. The DCT-DRTS sustained the drugs release and unlike DCT-hydrogel, the preliminary plasma concentration of DCT-DRTS was significantly reduced, overcoming the burst release. A meaningfully enhanced antitumor efficacy and improved survival rate was observed from DCT-DRTS in tumor cell xenograft athymic nude mice. Additionally, increased apoptotic and reduced proliferation markers were observed in DCT-DRTS treated tumor masses. It was concluded that DCT-DRTS may be a suitable choice for intramuscular administration of DCT with sustained release, improved bioavailability, reduced toxicity and enhanced antitumor effects. [Display omitted] • Docetaxel (DCT), has been used extensively for the treatment of various cancers. • We developed a novel sustained release formulation DCT-DRTS for intramuscular route. • DCT-DRTS was composed of thermosensitive solid lipid nanoparticle and hydrogel. • It demonstrated improved bioavailability, no toxicity and greater antitumor effects. • High apoptosis and reduced proliferation of tumor masses were observed in DCT-DRTS. [ABSTRACT FROM AUTHOR]

Aim: Breast cancer and its metastases involve high mortality even with advances in chemotherapy. Solid lipid nanoparticles provide a platform for drug delivery, reducing side effects and treatment-induced bone loss. A solid nanoparticle containing doxorubicin was evaluated for its ability to prevent bone loss in a pre-clinical breast cancer model. Methods: We investigated the effects of SLNDox in an aggressive metastatic stage IV breast cancer model, which has some important features that are interesting for bone loss investigation. This study evaluates bone loss prevention potential from solid lipid nanoparticles containing doxorubicin breast cancer treatment, an evaluation of the attenuation of morphological changes in bone tissue caused by the treatment and the disease and an assessment of bone loss imaging using computed tomography and electron microscopy. Results: Chemotherapy-induced bone loss was also observed in tumor-free animals; a solid lipid nanoparticle containing doxorubicin prevented damage to the growth plate and to compact and cancellous bones in the femur of tumor-bearing and healthy animals. Conclusion: The association of solid lipid nanoparticles with chemotherapeutic drugs with proven efficacy promotes the prevention of serious consequences of chemotherapy, reducing tumor progression, increasing quality of life and improving prognosis and survival. Graphical Abstract Article highlights The treatment of breast cancer leads to an imbalance in bone metabolism, promoting the reabsorption of the mineral portion of the tissue. The use of doxorubicin is widespread in the clinic, but it intensifies bone loss, reducing survival. The use of solid lipid nanoparticles containing doxorubicin is promising as a treatment capable of mitigating adverse effects. SLNDox prevented bone loss in mice, preventing the reduction of mineralization and changes in the architecture of long bones. When the treatment is administered to animals with tumors, SLNDox also prevents damage to the growth plate, in addition to calcium loss and reduction in cancellous bone volume. In addition to the benefits of using nanostructures to treat neoplasms, the potential for preventing long-term damage has been observed with the prevention of bone loss through: Reducing the concentration of doxorubicin in the kidneys and heart. Delaying tumor progression and the emergence of lung metastases. Preventing the destruction of cancellous bone. Preventing demineralization of bone tissue. [ABSTRACT FROM AUTHOR]

Mathematical modeling of drug release from drug delivery systems is crucial for understanding and optimizing formulations. This research provides a comparative mathematical analysis of drug release from lipid-based nanoparticles. Drug release profiles from various types of lipid nanoparticles, including liposomes, nanostructured lipid carriers (NLCs), solid lipid nanoparticles (SLNs), and nano/micro-emulsions (NEMs/MEMs), were extracted from the literature and used to assess the suitability of eight conventional mathematical release models. For each dataset, several metrics were calculated, including the coefficient of determination (R2), adjusted R2, the number of errors below certain thresholds (5%, 10%, 12%, and 20%), Akaike information criterion (AIC), regression sum square (RSS), regression mean square (RMS), residual sum of square (rSS), and residual mean square (rMS). The Korsmeyer-Peppas model ranked highest among the evaluated models, with the highest adjusted R2 values of 0.95 for NLCs and 0.93 for other liposomal drug delivery systems. The Weibull model ranked second, with adjusted R2 values of 0.92 for liposomal systems, 0.94 for SLNs, and 0.82 for NEMs/MEMs. Thus, these two models appear to be more effective in forecasting and characterizing the release of lipid nanoparticle drugs, potentially making them more suitable for upcoming research endeavors. [ABSTRACT FROM AUTHOR]

The objective of this research was to develop a topical formulation containing nanoparticles of zinc iodide for enhanced wound healing. Solid lipid nanoparticles (SLNs) of zinc iodide increased drug stability, solubility, drug release and enhance the wound healing action of drug. This is the reason behind of selection of this formulation concept designing. Solid lipid nanoparticles (SLNs) of zinc iodide were prepared using a modified emulsification-diffusion technique and optimized through Box-Behnken statistical design. The formulation involved lipid-soluble excipients, including glycerol monostearate, palmitic acid, and stearic acid, with polysorbate 80 as the surfactant. The optimized SLN formulations were characterized based on particle size, polydispersity index (PDI), zeta potential, entrapment efficiency and in vitro drug release. The optimized SLN formulations exhibited desirable characteristics in terms of particle size, PDI, zeta potential, entrapment efficiency, and sustained drug release. In vitro release studies demonstrated that SLNs provided a prolonged release of the drug compared to the zinc iodide solution, with release kinetics fitting the Higuchi model, indicating a time-dependent diffusion process. The SLNs loaded with zinc iodide showed enhanced wound healing when applied topically to rat wounds, maintaining drug release for up to 24 hours. The reduction in wound area was significant, indicating improved healing. Stability studies further confirmed that the SLN formulations remained stable over time, with no significant changes in their critical parameters. The study concludes that SLN formulations of zinc iodide are effective in promoting wound healing by providing controlled drug release and improved skin permeation. These findings highlight the potential of SLNs as an advanced delivery system for wound care, offering enhanced therapeutic outcomes through sustained drug release. [ABSTRACT FROM AUTHOR]

This study focuses on the preparation and evaluation of famotidine-loaded solid lipid nanoparticles (SLNs) for enhancing oral drug delivery. Famotidine, a commonly used H2 receptor antagonist for treating gastric acid-related conditions, faces challenges in oral administration due to its poor aqueous solubility and low bioavailability. To address these limitations, SLNs were formulated using a solvent emulsification-evaporation method, employing biocompatible lipids to encapsulate the drug and improve its absorption. The prepared SLNs were characterized for particle size, zeta potential, drug loading efficiency, and encapsulation efficiency. Results showed that the SLNs had an average particle size of 150 nm, a zeta potential of -25 mV, and a high drug encapsulation efficiency of 90%, ensuring stability and effective drug loading. Morphological analysis confirmed spherical nanoparticles with a smooth surface, supporting the uniformity of the formulation. In vitro release studies demonstrated a sustained drug release profile, with 60% of famotidine being released over a prolonged period, highlighting the potential of SLNs in maintaining therapeutic drug levels. Furthermore, pharmacokinetic evaluations indicated that the bioavailability of famotidine was significantly enhanced when delivered via SLNs compared to the free drug. These findings suggest that famotidine-loaded SLNs could be a promising approach for overcoming the limitations of oral famotidine delivery, offering improved bioavailability, stability, and controlled release, which could lead to better therapeutic outcomes in clinical settings. [ABSTRACT FROM AUTHOR]

Solid Lipid Nanoparticles (SLNs) have emerged as a promising drug delivery system for enhancing the solubility and bioavailability of lipophilic phytoconstituents, particularly in the treatment of Pulmonary Arterial Hypertension (PAH). PAH is a complex cardiovascular condition characterized by elevated pulmonary vascular resistance, leading to significant morbidity and mortality. Traditional therapeutic approaches often suffer from limitations in drug solubility and systemic side effects, necessitating innovative delivery strategies. This review explores the structural composition, drug loading mechanisms, and stability challenges of SLNs, highlighting their advantages over conventional formulations. The encapsulation of lipophilic phytoconstituents within SLNs not only improves their solubility, but also facilitates targeted delivery to the pulmonary system, maximizing therapeutic efficacy. Furthermore, SLNs offer a sustained release profile, enhancing the pharmacokinetic and pharmacodynamic properties of the encapsulated compounds. The implications of SLNs in addressing the pathophysiology of PAH, including their impact on pulmonary vascular resistance and endothelial function, are discussed. Despite challenges related to formulation scalability, regulatory hurdles and cost-effectiveness, the future prospects for SLNs in PAH management are promising, with potential applications in personalized medicine and combination therapies. This review underscores the transformative potential of SLNs in enhancing phytoconstituent delivery for PAH treatment. [ABSTRACT FROM AUTHOR]

Abstract Background The fabrication of anti-Toxoplasma drugs with less side effects and desirable efficacy is one of the important research goals facing with toxoplasmosis. This study aimed to determine the anti-Toxoplasma effects of Cinnamon zeylanicum (CZ), Moringa oleifera (MO) oil encapsulated into solid lipid nanoparticles (SLNs). Methods Vero cells were cultured with serial concentrations (1 mg/mL to 100 µg/mL) of CZ-SLNs and MO-SLNs in DMEM culture medium. The morphological, physical, and chemical features of nanoparticles were calculated. The cell viability assays and anti-T. gondii effects of CZ-SLNs and MO-SLNs were evaluated. The CC50 and IC50 indices of SLNs-enveloped extracts were calculated. Results The particle sizes of MO-SLNs and CZ-SLNs were 411.5 and 365 nm, while PDI indices were 0.53 and 0.7, respectively. Transmission electron microscopy (TEM) showed that both MO-SLNs and CZ-SLNs were smoothed spherical nanoparticles with rounded edges. The cytotoxicity assay showed the CC50 value of MO-SLNs at concentrations of ˃10 mg/mL. In addition, 60% of T. gondii-infected Vero cells remained alive at the concentrations ≤ 1 mg/ml, while the MO-SLNs killed at least 90% of T. gondii tachyzoites with an IC50 > 1 µg/ml. The cytotoxicity of CZ-SLNs extract showed the CC50 at the concentration 0.1 mg/mL. More than 50% of Vero cells, infected with T. gondii tachyzoites, survived at a concentration less than 0.1 mg/mL (IC50 ˂ 0.1 mg/mL), while the CZ-SLNs killed at least 85% of T. gondii tachyzoites in all concentrations. Conclusion The current results represented that the use of SLNs as a nano-carrier for M. oleifera and C. zeylanicum could kill T. gondii tachyzoites with low cytotoxicity, suggesting the effectiveness of these nano-emulsions along with the chemical agents in the treatment of Toxoplasma.

This study aimed to develop solid lipid nanoparticles containing 5-fluorouracil (5-FU loaded PGSLNs) to achieve desired physicochemical properties and to enhance in vitro cytotoxicity against monolayered and 3D spheroid skin tumor models. 5-FU loaded PGSLNs were prepared via cold homogenization using Glyceryl Palmitostearate (GP) and Geleol® as solid lipids and Poloxamer 188 and Tween 80 as surfactant and co-surfactant, respectively. The developed nanoparticles were then physicochemically characterized, and cytotoxicity was evaluated against monolayered and 3D spheroid skin tumor models using the Cell TiterBlue® Assay and Cell-Titre Glo assays, respectively. The cellular uptake behavior of nanoparticles against monolayered and 3D spheroid tumor models was studied through flow cytometric analysis and fluorescence microscopic analysis. Nanoparticle sizes ranged from 116.3 ± 1.19 to 235.13 ± 1.15 nm, with a PDI < 0.45, and zeta potential was found to be between − 33.67 ± 0.40 and − 19.37 ± 0.25. FTIR analysis revealed no chemical interactions among components, and Differential Scanning Calorimetry showed the thermal stability of the drug in nanoparticles. The in vitro drug release profile depicted biphasic release behavior, with 30–35% burst release within 3 h and sustained release for 48 h. Enhanced cytotoxicity was observed against monolayered skin tumor models (B16F10, A375, and A431) and a 3D spheroid skin tumor model (A431). Rhodamine-labeled PGSLNs showed increased uptake in monolayered models via fluorescence microscopy and flow cytometry, with enhanced uptake in 3D spheroid models confirmed by fluorescence microscopy. The hemocompatibility assay indicated the safety of nanoparticles at physiological levels. The designed solid lipid nanoparticles significantly enhanced the cytotoxic effect of 5-FU against monolayered and 3D spheroid skin tumor models and can be used as promising approach for skin cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: Epilepsy is a group of chronic neurological diseases caused by a complex set of neuronal hyper electrical activities and oxidative stress of neurons. Crocin is a natural bioactive agent of saffron with different pharmacological properties and low bioavailability. This study aimed to evaluate crocin-loaded solid lipid nanoparticles (SLNC) for neuroprotection activity and efficacy against pentylenetetrazol (PTZ)- induced epilepsy. Experimental approach: The rats were pretreated with SLNC and pure-crocin (PC; 25 and 50 mg/kg/day; P.O.) for 28 days before PTZ induction. Behavioral functions were evaluated by passive avoidance learning (PAL) tasks. Then, total antioxidant capacity (TAC), malondialdehyde (MDA), and pro-inflammatory factors were measured in the brain tissue using ELISA kits. Gene expression levels were analyzed with real-time polymerase chain reaction and immunohistochemical assay was used to assess the protein expression of sirtuin1 SIRT 1). Findings/Results: SLNC was prepared with an average particle size of 98.25 nm and 98.33% encapsulation efficiency. Memory deficit improved in rats treated with SLNC. Administering SLNC at 25 and 50 mg/kg significantly reduced MDA and proinflammatory cytokines while increasing TAC. Additionally, administering SLNC before treatment increased the levels of SIRT1, peroxisome proliferator-activated receptor coactivator 1α, cAMP-regulated enhancer binding protein, and brain-derived neurotrophic factor. Furthermore, SLNC administration resulted in the downregulation of caspase-3 and inflammation factor expression. Conclusion and implications: Overall, the obtained results showed that SLNC has better protective effects on oxidative stress in neurons, neurocognitive function, and anti-apoptotic and neuromodulatory activity than PC, suggesting that it is a promising therapeutic strategy for inhibiting seizures.

The creation of combined nanomedicines and their controlled release under the influence of photoinduction is an actively developing branch of scientific research. This work is devoted to the development of models of solid lipid nanoparticles for a well-known antitumor drug – gefitinib in combination with a photoindicating agent – a photosensitizer from the phthalocyanine group. Nanoparticles were obtained by several methods: hot homogenization with stearic acid, sesame oil and Tween 80 and by one-step dispersion with copolymers of lactic and glycolic acids and polyvinyl alcohol. In vitro experiments when irradiating particles with a laser in the near-infrared range (about 730 nm) proved the advantage of using combined nanoparticles with gefitinib and a photosensitizer compared to monotherapy, while the activity in terms of IC50 was 5.1-8.7 times higher for gefitinib and 1.5-1.8 times for the photosensitizer.

AbstractSkin flaps are employed to cover cutaneous denuded surfaces, but ensuing flap necrosis often occurs. Previously, rats with myocardial infarction treated with lipid-core nanoparticles (LDE) loaded with methotrexate (MTX) improved myocardial irrigation and reduced necrosis. Here, the aim was to investigate the efficacy of LDE-MTX to preserve the viability of cutaneous flaps and its implications for surgical wound healing. Twenty-eight male rats were divided into 4 groups: (1) LDE, injected intraperitoneally with LDE only; (2) MTX (1 mg/Kg commercial MTX): (3) LDE-MTX (1 mg/Kg MTX associated with LDE), and controls without treatment. LDE, MTX or LDE-MTX were repeated after 2 days. Then, flap surgery (9x3cm) was performed on the dorsal region. Injections were continued every other day until day 7 when animals were euthanized. LDE-MTX treatment improved the total viable area of the flaps with a fourfold increase in blood flow and reduced inflammatory cell number (p < 0.001), accompanied by decreased protein expression of pro-inflammatory factors. SOD-1 was higher in LDE-MTX-treated rats (p < 0.05). In conclusion, LDE-MTX treatment achieved total viability of cutaneous flaps, with increased irrigation and diminished local inflammation. LDE-MTX may offer efficient and cost-effective prevention of cutaneous flaps and treatment for wounds from surgical procedures to be tested in future clinical studies. [ABSTRACT FROM AUTHOR]

Solid lipid nanoparticles (SLNs) incorporated with retinol and oligopeptide can have a full spectrum of effects on the skin as a compatible combination of ingredients with broad anti-aging properties. The research's main objective was to ensure the stability of lipid nanocarriers containing retinol and peptide due to the planned use of this dispersion as a cosmetic raw material. To confirm the effectiveness of method optimization (high shear homogenization, HSH) and proper selection of substrates, SLN dispersions were obtained in three combinations: 1—non-incorporated SLNs; 2—SLNs containing only retinol; 3—SLNs containing retinol and pentapeptide-18; these were then stored at different temperatures (4, 25, 45 °C) for 4 weeks. The desired values of the physicochemical parameters of the optimized dispersion of lipid nanoparticles incorporated with retinol and oligopeptide over the required storage period were confirmed: mean particle size (Z-Ave) = 134.7 ± 0.3 nm; polydispersity index (PDI) = 0.269 ± 0.017 [−]; zeta potential (ZP) = 42.7 ± 1.2 mV (after 4 weeks at 25 °C). The results confirmed the proper selection of the SLN production method and the effectiveness of the optimization performed. The possibility of using the obtained raw material as an ingredient in cosmetic products with anti-aging properties was indicated. [ABSTRACT FROM AUTHOR]

In the pharmaceutical sector, solid lipid nanoparticles (SLN) are vital for drug delivery incorporating a lipid core. Chondroitin sulfate (CHON) is crucial for cartilage health. It is often used in osteoarthritis (OA) treatment. Due to conflicting results from clinical trials on CHON's efficacy in OA treatment, there has been a shift toward exploring effective topical systems utilizing nanotechnology. This study aimed to optimize a solid lipid nanoparticle formulation aiming to enhance CHON permeation for OA therapy. A 3 × 3 × 2 Design of these experiments determined the ideal parameters: a CHON concentration of 0.4 mg/mL, operating at 20,000 rpm speed, and processing for 10 min for SLN production. Transmission electron microscopy analysis confirmed the nanoparticles' spherical morphology, ensuring crucial uniformity for efficient drug delivery. Cell viability assessments showed no significant cytotoxicity within the tested parameters, indicating a safe profile for potential clinical application. The cell internalization assay indicates successful internalization at 1.5 h and 24 h post-treatment. Biopharmaceutical studies supported SLNs, indicating them to be effective CHON carriers through the skin, showcasing improved skin permeation and CHON retention compared to conventional methods. In summary, this study successfully optimized SLN formulation for efficient CHON transport through pig ear skin with no cellular toxicity, highlighting SLNs' potential as promising carriers to enhance CHON delivery in OA treatment and advance nanotechnology-based therapeutic strategies in pharmaceutical formulations. [ABSTRACT FROM AUTHOR]

Superoxide dismutase (SOD), a natural enzyme with high antioxidant activity, reduces injury and accelerates wound healing by scavenging superoxide radicals. This enzyme plays an important role in cellular defense against oxidative stress such as burn injury. The aim of this study was to load SOD into solid lipid nanoparticles for the treatment of rat burn wounds. Solid lipid nanoparticles were prepared by Solvent Emulsification Diffusion method and evaluated for particle size, enzyme activity and enzyme entrapment efficiency. Twenty-seven rats in 3 different groups were induced with deep second-degree burns and then treated with SOD-loaded solid lipid nanoparticles, solid lipid nanoparticles without enzyme, or SOD solution. After the treatment period, the wounds were evaluated macroscopically for the area of healing and microscopically for indices of re-epithelialization, granulation tissue and angiogenesis. The optimized SOD-loaded solid lipid nanoparticles showed a particle size of 35–85 ± 2.41 nm, 78.4 ± 4.31 % entrapment efficiency and 90 % initial enzyme activity. Macroscopic examination showed that the best recovery rate belonged to the solid lipid nanoparticle group. Pathological studies also showed that angiogenesis and granulation tissue were significantly better in this group. Compared to the other two groups, SOD-loaded solid lipid nanoparticles showed a significant improvement in pathological factors, particularly angiogenesis and granulation tissue, as well as a faster reduction in the number of inflammatory cells. Based on this study, solid lipid nanoparticles could be used as an effective delivery system for SOD in the treatment of second-degree burns. • One of the new strategies in the development of the pharmaceutical industry is the use of nanotechnology. • The use of solid lipid nanoparticles as a novel drug delivery system to deliver superoxide dismutase to second-degree burns. • The system can help the enzyme penetrate into the deep layers of the skin, therefore more effective in the treatment of burns. • The system can protect the enzyme against environmental deteriorations. • The enzyme released from such carrier is slow and sustained so that there is no need to repeated doses. [ABSTRACT FROM AUTHOR]

The aim of the current study was to fabricate and optimize solid lipid nanoparticles (SLNs) loaded topical hydrogel for the treatment of infantile hemangioma (IH). Propranolol is used to treat IH; however, its systemic use has several worsening side effects in infants. To cope with this problem, a novel topical formulation was designed. Firstly, propranolol was desalted, and Precirol solid lipid nanoparticles (SLNs) were fabricated by utilizing hot emulsion technique. The response surface methodology was used for optimization of nanoparticles. The optimized nanoformulation was characterized for its particle diameter, zeta potential, surface morphology, entrapment efficiency, crystallinity, and molecular interaction. Afterwards, these nanoparticles were loaded into Carbopol hydrogel for topical drug delivery. In vitro release and ex vivo permeation studies were also conducted to gauge the potential of SLNs loaded hydrogel. The optimized formulation exhibited particle size of approximately 130 nm with PDI of 0.232 and zeta potential of − 22.9 mV. Crystallinity studies and Fourier transform infrared (FTIR) analysis revealed no molecular interaction. This novel hydrogel can play a crucial role in controlling the IH in neonates. [ABSTRACT FROM AUTHOR]

The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of olanzapine (OLZ) loaded solid lipid nanoparticles (SLNs) for sustained release. OLZ SLNs were prepared by hot melt emulsification and ultrasonication using Precirol ATO 5 (PRE) as a solid lipid, combination of Kolliphor ELP (KELP) and Tween 80 (T80) as surfactants, after optimising formulation and process variables. The SLN system was subjected to evaluation of particle size, zeta potential, entrapment efficiency (EE), in-vitro drug release and ex-vivo intestinal permeability studies using the chicken intestinal segments (jejunum). Further, these SLNs were converted into stable DANs by adsorbing onto a Neusilin US2 (NUS2) and Avicel CL 611 (ACL) carriers using the granulation-evaporative drying method. The DANs were characterised for redispersion properties, in-vitro drug release, thermal behaviour, crystallinity, and morphology. The SLN and DAN had a particle size of 238.0 nm [0.274 polydispersity index (PdI)] and 302.4 [0.494 PdI] respectively. The zeta potentials of SLN and DAN were found to be −29.3 mV and −26.3 mV, respectively. The SLN had 67% EE, and showed a sustained drug release in various media. The highest permeability of SLNs was observed in ex-vivo permeation model compared to the OLZ suspension, indicating that SLNs have the potential to bypass hepatic metabolism. The adsorption of SLNs onto carriers was confirmed by surface morphology. The DAN had good flow properties and sustained drug release similar to that of SLNs. The X-ray diffraction (XRD) patterns and endothermic peaks confirmed the complete encapsulation of actives in lipid matrices. The encapsulating of OLZ in SLNs and converting it into DAN showed a sustained release and adsorption technique that can be used for improving the stability of NLC dispersion. The DANs can be offered in dosage forms such as filling into sachets, capsules and compressed into tablets. [ABSTRACT FROM AUTHOR]

Vitamin K derivatives such as menadione (MD) have been recognized as promising redox-modulating and chemosensitizing agents for anticancer therapy, however, their cellular activities in peptide-targeted nanocarriers have not been elucidated to date. This study provides the guidelines for developing MD-loaded solid lipid nanoparticles (SLN) modified with extracellular matrix (ECM)-derived peptides. Relationships between RGD peptide concentration and changes in DLS characteristics as well as accumulation of SLN in cancer cells were revealed to adjust the peptide-lipid ratio. SLN system maintained adequate nanoparticle concentration and low dispersity after introduction of MD and MD/RGD, whereas formulated MD was protected from immediate conjugation with reduced glutathione (GSH). RGD-modified MD-containing SLN showed enhanced prooxidant, GSH-depleting and cytotoxic activities toward PC-3 prostate cancer cells attributed to improved cellular pharmacokinetics of the targeted formulation. Furthermore, this formulation effectively sensitized PC-3 cells and OVCAR-4 ovarian cancer cells to free doxorubicin and cisplatin so that cell growth was inhibited by MD–drug composition at nontoxic concentrations of the ingredients. These results provide an important background for further improving chemotherapeutic methods based on combination of conventional cytostatics with peptide-targeted SLN formulations of MD. [Display omitted] • ECM peptide-targeted menadione-loaded solid lipid nanoparticles were developed. • Characteristics of RGD peptide-targeted SLN were optimized for delivery into cancer cells. • Cellular effects of SLN formulation of menadione were studied for the first time. • The formulation showed enhanced peptide-mediated prooxidant and GSH-depleting activities. • The formulation promoted cytotoxicity of doxorubicin and cisplatin at nontoxic concentrations. [ABSTRACT FROM AUTHOR]

Macrophages are employed as targets for delivering genes, drugs, or lipid nanoparticles into tumors or other specific sites. Studying the interaction between solid lipid nanoparticles (SLNs) and macrophages is essential for assessing nanotoxicity and advancing the development of nanomedicines. However, limited data are currently available on the membrane microstructure and biochemical changes that occur when macrophages interact with SLNs. We conducted a label-free morphological and biochemical investigation of NR8383 macrophages using optical diffraction tomography (ODT), which validated the efficiency of the SLNs as a drug delivery system. ODT provided intracellular holotomography to characterize the macrophages and fluorescence imaging to analyze delivery efficiency. ODT analysis revealed the responses of phagocytic macrophages. Additionally, a quantitative analysis of lipid droplets using refractive indices revealed that, compared with incubation with normal cells, incubation with SLNs significantly increased the lipid droplet volume and surface area. The uptake of SLNs into macrophages resulted in increased cell volume, surface area, and concentration, which indicated greater morphological and biochemical variability in the treated cells than in the control cells. The results suggest that ODT imaging is promising for understanding the intracellular distribution of SLNs and useful for validating the efficacy of delivery of SLNs to macrophages. [Display omitted] • We conducted a label-free morphological and biochemical investigation of alveolar macrophages after treating with solid lipid nanoparticles (SLNs) using optical diffraction tomography (ODT). • Incubation with SLNs significantly increased the volume and surface area of lipid droplets as well as cell volume and surface area of the macrophages compared to normal cells. • The ODT imaging holds promise for understanding the intracellular distribution of SLNs and is valuable for validating the efficacy of SLNs delivery to macrophages. [ABSTRACT FROM AUTHOR]

Cerebrovascular and neurological diseases are characterized by neuroinflammation, which alters the neurovascular unit, whose interaction with the choroid plexus is critical for maintaining brain homeostasis and producing cerebrospinal fluid. Dysfunctions in such process can lead to conditions such as idiopathic normal pressure hydrocephalus, a common disease in older adults. Potential pharmacological treatments, based upon intranasal administration, are worthy of investigation because they might improve symptoms and avoid surgery by overcoming the blood–brain barrier and avoiding hepatic metabolism. Nasal lipid nanocarriers, such as solid lipid nanoparticles, may increase the nasal retention and permeation of drugs. To this aim, green solid lipid nanoparticles, obtained by coacervation from natural soaps, are promising vehicles due to their specific lipid matrix composition and the unsaponifiable fraction, endowed with antioxidant and anti-inflammatory properties, and thus suitable for restoring the neurovascular unit function. In this experimental work, such green solid lipid nanoparticles, fully characterized from a physico-chemical standpoint, were loaded with a drug combination suitable for reverting hydrocephalus symptoms, allowing us to obtain a non-toxic formulation, a reduction in the production of the cerebrospinal fluid in vitro, and a vasoprotective effect on an isolated vessel model. The pharmacokinetics and biodistribution of fluorescently labelled nanoparticles were also tested in animal models. [ABSTRACT FROM AUTHOR]

Skin carcinoma remains one of the most widespread forms of cancer, and its global impact continues to increase. Basal cell carcinoma, melanoma, and squamous cell carcinoma are three kinds of cutaneous carcinomas depending upon occurrence and severity. The invasive nature of skin cancer, the limited effectiveness of current therapy techniques, and constraints to efficient systems for drug delivery are difficulties linked with the treatment of skin carcinoma. In the present era, the delivery of drugs has found a new and exciting horizon in the realm of nanotechnology, which presents inventive solutions to the problems posed by traditional therapeutic procedures for skin cancer management. Lipid-based nanocarriers like solid lipid nanoparticles and nanostructured lipid carriers have attracted a substantial focus in recent years owing to their capability to improve the drug's site-specific delivery, enhancing systemic availability, and thus its effectiveness. Due to their distinct structural and functional characteristics, these nanocarriers can deliver a range of medications, such as peptides, nucleic acids, and chemotherapeutics, via different biological barriers, such as the skin. In this review, an effort was made to present the mechanism of lipid nanocarrier permeation via cancerous skin. In addition, recent research advances in lipid nanocarriers have also been discussed with the help of in vitro cell lines and preclinical studies. Being a nano size, their limitations and toxicity aspects in living systems have also been elaborated. [ABSTRACT FROM AUTHOR]

The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus with current universal importance represents a main carrier of emerging antimicrobial resistance determinatives of global health concerns that have developed drug resistance mechanisms to the various available antibiotics. On the other hand, due to the antimicrobial potential of Nigella Sativa oil (NSO), it was hypothesized that incorporation of nano-carriers (NS-SLN and NS-chitosan (CH) nanoparticles) can enhance its antibacterial effects. This study evaluated the physico-chemical and antibacterial characteristics of NS-SLN and NS-CH. TEM images revealed a round shape with clear edges for both nanoparticles, and the average sizes were reported to be 196.4 and 446.6 nm for NS-SLN and NS-CH, respectively. The zeta potential and encapsulation efficiency were −28.9 and 59.4 mV and 73.22% and 88% for NS-SLN and NS-CH, respectively. The Minimum Inhibitory Concentrations for NSO, NS-SLN, and NS-CH against S. aureus were 480, 200, and 80 µg/mL, respectively. The results confirm significantly stronger antibacterial influences of NSO when loaded into chitosan nanoparticles as a potential candidate for nano-delivery of antimicrobial agents. [ABSTRACT FROM AUTHOR]

Aim: The study explores the synergistic potential of atorvastatin (ATR) and quercetin (QUER)- loaded solid lipid nanoparticles (SLN) in combating breast cancer. Materials & methods: SLNs were synthesized using a high-shear homogenization method and optimized using Box-Behnken design. The SLNs were characterized and evaluated for their in vitro anticancer activity. Results: The optimized SLN exhibited narrow size distribution (PDI = 0.338 ± 0.034), a particle size of 72.5 ± 6.5 nm, higher entrapment efficiency (<90%), sustained release and spherical surface particles. The in vitro cytotoxicity studies showed a significant reduction in IC50 values on MDA-MB-231 cell lines. Conclusion: We report a novel strategy of repurposing well-known drugs and encapsulating them into SLNs as a promising drug-delivery system against breast cancer. Article highlights Drug repurposing presents a viable approach for advancing cancer treatment by utilizing existing drugs with established safety records and biological effects. The present study reports on the development and comprehensive investigation of a dual drug-loaded system (containing both quercetin and atorvastatin) as an innovative drug-delivery platform for the effective treatment of breast cancer. Atorvastatin is primarily linked to altering lipogenesis by which it is able to induce apoptosis, suppress angiogenesis and inhibit tumor cell proliferation and metastasis. Along with quercetin, a naturally occurring flavonoid also complements atorvastatin by disrupting metabolic processes like fatty acid and cholesterol synthesis thereby acting as an anticancer agent. Box-Behnken design was used to prepare and optimize dual drug-loaded solid lipid nanoparticles (SLN) (atorvastatin and quercetin) with the hypothesis that this would solve the issue with single therapies and enhance their therapeutic outcomes. Advanced analytical techniques including dynamic light scattering, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder x-ray diffraction, field emission scanning electron microscopy (FE-SEM) and atomic force microscopy (AFM) were used to characterize the optimized SLN. A sensitive and robust reversed phase-high performance liquid chromatography (RP-HPLC) method was developed for simultaneous estimation of both the drugs from the SLN matrix and to observe their dissolution behavior. A sustained release profile that outperformed the drugs from the SLN matrix and had release kinetics that followed the Higuchi model was revealed by in vitro drug-release research. The in-vitro cytotoxicity study demonstrated the synergistic effect of atorvastatin and quercetin SLNs against MDA-MB-231, surpassing the efficacy of the individual drug effect. [ABSTRACT FROM AUTHOR]

Purpose: In the current investigation, an ultrasonic approach was performed to produce menadione sodium bisulfite-loaded solid lipid nanoparticles (MSB-SLNs) with rhamnolipid as bio-surfactant, which aimed to increase the dermal delivery and anti-pigmentation effect. Methods: To achieve optimum delivery for MSB, the impact of the ratio of two surfactants (rhamnolipid: Tween) on nanoparticle attributes and the respective functions were evaluated. In vitro diffusion process, in vitro cytotoxicity assay, determination of melanin content of melanoma cells, L-DOPA auto-oxidation inhibitory test, and skin irritation studies carried out to investigate the suitability of MSB formulation in dermal application. Results: The optimized nanoparticles showed an average particle size, zeta potential, polydispersity index (PDI), and drug entrapment efficiency of 117.26±1.12 nm, -6.28±0.33 mV, 0.262±0.002, 83.34±0.75% respectively in hydrophilic-lipophilic balance (HLB) of 12. The in vitro diffusion process demonstrated that MSB-SLN gel had a prolonged release pattern. The levels of MSB in the cutaneous layers (52.192±2.730% or 961.59±50.313 μg/cm2) and the receiver compartment (23.721±1.803 % or 437.049± 33.236 μg/cm2) for the MSB-SLN gel was higher than MSB simple and showed no cutaneous irritancy and toxicity in rats. MSB-SLN inhibited melanin formation and was remarkably higher than free MSB. MSB-SLN inhibited L-3,4- dihydroxyphenylalanine (L-DOPA) auto-oxidation to a greater extent (95.14±1.46%) than MSB solution (72.28±0.83%). Conclusion: This study's observations revealed that the produced MSB-SLN might be used as a potential nano-vehicle for MSB dermal administration, thereby opening up innovative options for the management of hyper-melanogenesis problems. [ABSTRACT FROM AUTHOR]

Pneumonia stands as the leading infectious cause of childhood mortality annually, underscoring its significant impact on pediatric health. Although dexamethasone (DXMS) is effective for treating pulmonary inflammation, its therapeutic potential is compromised by systemic side effects and suboptimal carrier systems. To address this issue, the current study introduces solid lipid nanoparticles encapsulating hydrophobic dexamethasone palmitate (DXMS-Pal-SLNs) as an anti-inflammatory nanoplatform to treat pneumonia. The specialized nanoparticle formulation is characterized by high drug loading efficiency, low drug leakage and excellent colloidal stability in particular during nebulization and is proficiently designed to target alveolar macrophages in deep lung regions via local delivery with the nebulization administration. In vitro analyses revealed substantial reductions in the secretions of tumor necrosis factor-α and interleukin-6 from alveolar macrophages, highlighting the potential efficacy of DXMS-Pal-SLNs in alleviating pneumonia-related inflammation. Similarly, in vivo experiments showed a significant reduction in the levels of these cytokines in the lungs of mice experiencing lipopolysaccharide-induced pulmonary inflammation after the administration of DXMS-Pal-SLNs via nebulization. Furthermore, the study demonstrated that DXMS-Pal-SLNs effectively control acute infections without causing pulmonary infiltration or excessive recruitment of immunocytes in lung tissues. These findings highlight the potential of nebulized DXMS-Pal-SLNs as a promising therapeutic strategy for mitigating pneumonia-related inflammations. [ABSTRACT FROM AUTHOR]

Background: Trichinosis is acquired through ingesting the infective larvae in pork meat. Drugs employed for the treatment of trichinosis have a limited bioavailability in addition to the adverse side effects. In the current work, the therapeutic effect of ivermectin against experimental muscle trichinosis was evaluated using solid lipid nanoparticles with and without albendazole. Methods: Seven groups of ten albino mice each were created from the 70 total. (GI): normal control, (GII): infected, non-treated, and (GIII): infected treated with albendazole, (GIV): infected treated with ivermectin. (GV) infected treated with solid lipid nanoparticles, (GVI): infected treated with ivermectin loaded on solid lipid nanoparticles, and (GVII): infected and received a combination of albendazole and solid lipid nanoparticles loaded with ivermectin. For the sevenday intestinal phase and the 49-day muscle phase, each group was split into two subgroups of five mice each. The focus of this study is the muscular phase. The mean number of encysted larvae in the muscle tissue was counted for a parasitological evaluation. Using feulgen and hematoxylin and eosin (H&E) stains, all groups were assessed histopathologically and histochemically, respectively. Liver and kidney parameters were also assessed biochemically. Results: The treatment that combined the use of albendazole and ivermectin loaded on solid lipid nanoparticles (GVII) produced the greatest decrease in the count of encysted muscle larvae (92.16%). The improvement in histological, histochemical, and biochemical markers supported these findings. Conclusion: Ivermectin loaded on solid lipid nanoparticles (SLNPS) could be an additional or synergistic therapeutic agent in treating trichinosis. [ABSTRACT FROM AUTHOR]

Diacerein (DCN) is used mainly to treat degenerative diseases, such as osteoarthritis. DCN is marketed commercially in solid dosage forms. Liquid formulations of diacerein (DCN) have been hindered by its poor chemical stability in aqueous media. This work aims to develop a novel, stable, oral, liquid preparation of DCN having a concentration of 50 mg/5 ml. Solid lipid nanoparticles (SLNs) of DCN were prepared using cetyl alcohol as the lipid matrix and Tween 80® as a surfactant. A quality-by-design approach was utilized to optimize DCN-SLNs. The optimum DCN-SLNs were dispersed in a structured vehicle to formulate the liquid dosage form. This liquid preparation was subjected to accelerated stability studies at 40 °C and 75% RH for 6 months. The potential of the liquid preparation to minimize the diarrheal effect of DCN was assessed. Optimum concentrations of cetyl alcohol (2%) and Tween 80® (0.9%) were chosen to obtain the desired characteristics of SLNs. Interestingly, we determined that 0.05% of citric acid was the maximum concentration that can be added to the liquid preparation of diacerein to modify its pH without compromising its stability. The results of the stability studies show that the liquid preparation was robust and it withstood storage conditions (40 °C, 75% RH) for 6 months. The encapsulation of diacerein helps to protect it from degradation and significantly reduced the occurrence of diarrhea as a side effect (p < 0.0001). Liquid preparations of DCN-SLNs can thus be marketed as a new dosage form. [ABSTRACT FROM AUTHOR]

This study presents the synthesis and optimization of Methylene polyethyl glycol −Polystyrene (mPEG-PS) Diblock (DIP) copolymer-based solid lipid nanoparticles (SLNs) using ultrasonication for advanced drug delivery systems targeting the human immunodeficiency virus (HIV-1). The mPEG-PS block copolymer was synthesized by ring opening polymerization mechanism under nitrogen atmosphere for 24hrs and characterized using Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy and NMR, confirming the formation of DIP polymers. Optimization of SLNs formulation was achieved through a systematic approach, utilizing response surface methodology, optimal conditions for SLNs synthesis were determined, resulting in nanoparticles with a particle size of 198 nm and an entrapment efficiency of 67.42 %. Cell viability assays, quantitative PCR for viral DNA analysis, caspase-3 enzyme assays, and quantitative uptake studies using High Performance Liquid Chromatography (HPLC) provided quantitative insights into the efficacy and biocompatibility of the synthesized nanoparticles. The experimental data demonstrate that nanoparticle treatments significantly influence cellular responses, providing valuable insights into their therapeutic potential and underlying mechanisms. By employing precise experimental methods alongside rigorous analytical techniques, this study enhances our understanding of nanoparticle-based drug delivery systems, particularly in the context of HIV treatment. These findings pave the way for optimizing therapeutic strategies to improve patient outcomes.

Co-delivery strategies have become an integral active delivery approach, although understanding of how the microstructural characteristics could be deployed to achieve independently regulated active co-delivery profiles, is still an area at its infancy. Herein, the capacity to provide such control was explored by utilizing Pickering emulsions stabilized by lipid particles, namely solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). These dual functional species, regarding their concurrent Pickering stabilization and active carrying/delivery capabilities, were formulated with different solid lipid and surfactant types, and the effect on the release and co-release modulation of two hydrophobic actives separately encapsulated within the lipid particles themselves and within the emulsion droplets was investigated. Disparities between the release profiles from the particles in aqueous dispersions or at an emulsion interface, were related to the specific lipid matrix composition. Particles composed of lipids with higher oil phase compatibility of the emulsion droplets were shown to exert less control over their release regulation ability, as were particles in the presence of surfactant micelles in the continuous phase. Irrespective of their formulation characteristics, all particles provided a level of active release control from within the emulsion droplets, which was dependant on the permeability of the formed interfacial layer. Specifically, use of a bulkier particle surfactant or particle sintering at the droplet interface resulted in more sustained droplet release rates. Compared to sole release, the co-release performance remained unaffected by the co-existence of the two hydrophobic actives with the co-release behavior persisting over a storage period of 1 month.

IntroductionGlioblastoma is a grade IV solid brain tumor and has a 15-month survival rate even after treatment. Glioblastoma development is heavily influenced by retinoblastoma protein (pRB) pathway changes. The blood–brain barrier, drug resistance, and severe toxicity of Temozolamide are key obstacles in treating glioblastoma. Innovative treatments targeting the pRB pathway with efficient delivery vehicles are required to treat glioblastoma.MethodsFor this purpose, a library of 691 plant extracts previously tested in vitro for anti-cancerous, anti inflammatory, and anti-proliferative characteristics was created after thorough literature investigations. Compounds were docked against pRB pathway protein ligands using molecular operating environment and chimera. Their nuclear structure and drug-like properties were predicted through Lipinski rule and density functional theory analysis. Physio-chemical characterizations of naked and drug-encapsulated SLNPs assessed size, stability, entrapment efficiency, and drug release rate. Anti-cancer potential of drug and drug- loaded SLNPs was evaluated using U87, U251, and HEK cell lines. Formulations were tested for cancer cell metastatic potential using cell migration assays.ResultsSilymarin (Sil) was identified as the most potent compound against CDK4, which was then encapsulated in stearic acid solid lipid nanoparticles (SLNP-Sil). Sil showed decreased cell viability 72 h after treatment against both U87 and U251 cell lines but had negligible cytotoxic effect on HEK-293. IC50 value of Sil was 155.14 µM for U87 and 195.93 µM for U251. Sil and SLNP-Sil effectively inhibited U87 and U251 cell migration 24 h after treatment.DiscussionOur results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit in vivo experimental verification using orthotropic xenograft mouse models against glioblastoma.

Disruption in the wound-healing process is caused by the presence of bacteria and leads to major problems and delays in wound healing. The limitations of commonly used medicines for treating wound infections include drug toxicity, insufficient microbial coverage, poor penetration, and increased resistance. This study aimed to determine the effect of ciprofloxacin loaded in solid lipid nanoparticles (Cip-SLN) on Pseudomonas aeruginosa and ampiciliin-vancomycin loaded in solid lipid nanoparticles (Amp-Van-SLN) on Staphylococcus aureus in wounds. Antibiotics were encapsulated in SLNs using the double emulsion method and were characterized. The in-vitro effect of antibiotic-loaded nanoparticles on P. aeruginosa and S. aureus was assessed using well diffusion and MIC methods. Finally, the topical antibacterial activity of these nanoparticles against bacterial wound infection was measured in a mouse model. MIC results showed that in the first 24 hours, the free drug had a greater effect on inhibiting bacteria, and in 72 hours, the inhibitory effect of nanoparticles increased. There was no toxicity effect of 400 µg/mL of nanoparticles on cells. According to the findings, the groups treated with Cip-SLN and Amp-Van-SLN were more effective than the control group (untreated) in different concentrations. In the wound healing process, the group treated with solid lipid nanoparticles (SLNs) exhibited a greater epithelial thickness, indicating enhanced healing, compared to the group treated with the free drug. The use of SLN can increase the accumulation of antibiotics at the site of infection with a slow release of the drug due to its fatty nature, which leads to a significant inhibitory effect on bacteria and also improves wound healing.

IntroductionThis study aimed to prepare cholesterol and stearic acid-based solid lipid nanoparticles of gabapentin (GAB-SLNs) for protection against streptozotocin (STZ)-induced retinal injury in rats.MethodsWe prepared four preparations of GAB-SLNs using a hot high-shear homogenization ultrasonication process, and the best formulation was selected and tested for biological activity. The retinal injury was brought in male adult albino rats while gabapentin doses continued for 6 weeks. Six groups of rats were assigned as the vehicle, diabetic, diabetic + gabapentin (10–20 mg/kg), and diabetic + GAB-SLNs (10–20 mg/kg). GAB-SLN#2 was selected as the optimized formulation with high entrapment efficacy (EE%, 98.64% ± 1.97%), small particle size (185.65 ± 2.41 nm), high negative Zeta potential (−32.18 ± 0.98 mV), low polydispersity index (0.28 ± 0.02), and elevated drug release (99.27% ± 3.48%). The TEM image of GAB-SLN#2 revealed a smooth surface with a spherical shape.ResultsGAB-SLNs provided greater protection against retinal injury than free gabapentin as indicated by the histopathology data which demonstrated more organization of retinal layers and less degeneration in ganglion cell layer in rats treated with GAB-SLN#2. Further, GAB-SLN#2 reduced the inflammatory proteins (IL-6/JAK2/STAT3) and vascular endothelial growth factor (VEGF).ConclusionThe preparation of GAB-SLNs enhanced the physical properties of gabapentin and improved its biological activity as a neuroprotectant. Further studies are warranted to validate this technique for the use of oral gabapentin in other neurological disorders.