Blank Solid Lipid Nanoparticles Research Articles

Evaluation of Drug-Loaded and Surface-Adsorbed DNase/Tween-80 Solid Lipid Nanoparticles against Staphylococcus aureus Biofilms.

The aim of this study was to explore the suitability of Tween-80 or DNase I adsorbed onto the surface of gentamicin-loaded solid lipid nanoparticles (SLNs) to disrupt Staphylococcus aureus biofilms in vitro. We hypothesized that surface-adsorbed DNase I or Tween-80 of SLNs will degrade the biofilm component, extracellular DNA (e-DNA), and extracellular matrix (ECM) of S. aureus biofilms. The SLNs loaded with drug (core) and surface-adsorbed disruptors (Tween-80 or DNase I) to deliver biofilm disruptors first at the site of action, which will help to break down the biofilm, and further drug release from the core will easily penetrate the biofilm and facilitate the killing of bacteria residing in S. aureus biofilms. The SLNs were synthesized by the double emulsion method; the size was 287.3 ± 7.4 nm for blank SLNs and 292.4 ± 2.36 nm for drug-loaded SLNs. The ζ-potential of blank SLNs was -25.6 ± 0.26 mV and that of drug-loaded SLNs was -13.16 ± 0.51 mV, respectively. The successful adsorption of DNase I or Tween-80 was confirmed by the activity of DNase I in blank surface-adsorbed SLNs and the change in the ζ-potential of SLNs after adsorbing DNase I or Tween-80. The surface morphology and size of the SLNs were further characterized using scanning electron microscopy. The encapsulation efficiency of the drug was 16.85 ± 0.84%. The compatibility of the drug with the excipient was confirmed by Fourier transform infrared spectroscopy and the degree of crystallinity was confirmed by X-ray diffraction (XRD) analysis. SLNs showed a sustained release of the drug up to 360 h. SLNs were easily taken up by A549 cells with minimal or no toxicity. The present study showed that Tween-80- or DNase I-adsorbed SLNs efficiently disrupt S. aureus biofilms and possess no or minimal toxicity against cells and red blood cells (RBCs).

Bedaquiline-Loaded Solid Lipid Nanoparticles Drug Delivery in the Management of Non-Small-Cell Lung Cancer (NSCLC).

Non-small-cell lung cancer (NSCLC) mortality and new case rates are both on the rise. Most patients have fewer treatment options accessible due to side effects from drugs and the emergence of drug resistance. Bedaquiline (BQ), a drug licensed by the FDA to treat tuberculosis (TB), has demonstrated highly effective anti-cancer properties in the past. However, it is difficult to transport the biological barriers because of their limited solubility in water. Our study developed a UPLC method whose calibration curves showed linearity in the range of 5 ng/mL to 500 ng/mL. The UPLC method was developed with a retention time of 1.42 and high accuracy and precision. Its LOQ and LOD were observed to be 10 ng/mL and 5 ng/mL, respectively, whereas in the formulation, capmul MCM C10, Poloxamer 188, and PL90G were selected as solid lipids, surfactants, and co-surfactants, respectively, in the development of SLN. To combat NSCLC, we developed solid lipid nanoparticles (SLNs) loaded with BQ, whereas BQ suspension is prepared by the trituration method using acacia powder, hydroxypropyl methylcellulose, polyvinyl acrylic acid, and BQ. The developed and optimized BQ-SLN3 has a particle size of 144 nm and a zeta potential of (-) 16.3 mV. whereas BQ-loaded SLN3 has observed entrapment efficiency (EE) and loading capacity (LC) of 92.05% and 13.33%, respectively. Further, BQ-loaded suspension revealed a particle size of 1180 nm, a PDI of 0.25, and a zeta potential of -0.0668. whereas the EE and LC of BQ-loaded suspension were revealed to be 88.89% and 11.43%, respectively. The BQ-SLN3 exhibited insignificant variation in particle size, homogeneous dispersion, zeta potential, EE, and LC and remained stable over 90 days of storage at 25 °C/60% RH, whereas at 40 °C/75% RH, BQ-SLN3 observed significant variation in the above-mentioned parameters and remained unstable over 90 days of storage. Meanwhile, the BQ suspension at both 25 °C (60% RH) and 40 °C (75% RH) was found to be stable up to 90 days. The optimized BQ-SLN3 and BQ-suspension were in vitro gastrointestinally stable at pH 1.2 and 6.8, respectively. The in vitro drug release of BQ-SLN3 showed 98.19% up to 12 h at pH 7.2 whereas BQ suspensions observed only 40% drug release up to 4 h at pH 7.2 and maximum drug release of >99% within 4 h at pH 4.0. The mathematical modeling of BQ-SLN3 followed first-order release kinetics followed by a non-Fickian diffusion mechanism. After 24 to 72 h, the IC50 value of BQ-SLN3 was 3.46-fold lower than that of the BQ suspension, whereas the blank SLN observed cell viability of 98.01% and an IC50 of 120 g/mL at the end of 72 h. The bioavailability and higher biodistribution of BQ-SLN3 in the lung tumor were also shown to be greater than those of the BQ suspension. The effects of BQ-SLN3 on antioxidant enzymes, including MDA, SOD, CAT, GSH, and GR, in the treated group were significantly improved and reached the level nearest to that of the control group of rats over the cancer group of rats and the BQ suspension-treated group of rats. Moreover, the pharmacodynamic activity resulted in greater tumor volume and tumor weight reduction by BQ-SLN3 over the BQ suspension-treated group. As far as we are aware, this is the first research to look at the potential of SLN as a repurposed oral drug delivery, and the results suggest that BQ-loaded SLN3 is a better approach for NSCLC due to its better action potential.

Effects of Sufentanil Nanoparticles on Proliferation and Apoptosis of Human Lung Adenocarcinoma Cells

This research was aimed to investigate the effects of sufentanil nanoparticles (Suf-NPs) on the proliferation and apoptosis of human lung adenocarcinoma (LUAD) cells, and to provide theoretical support for future drug therapy. Based on the preparation method of solid lipid nanoparticles (SLN), stearic acid and lecithin were used as materials to prepare Suf-NPs. The physical and chemical properties of Suf-NPs were analyzed by scanning electron microscope and particle size analyzer. A549 human LUAD cell line was selected. According to different cell treatment methods, A549 cells were randomly divided into control (Con), sufentanil (Suf), blank SLN, and Suf-NPs groups. Con was cultured routinely, and Suf group was treated with 0.02 μg/mL sufentanil. Suf-NPs group was treated with Suf-NPs, and the concentration was the same as that in the Suf group. The SLN group was added with blank SLN suspension. CCK8 assay was adopted to test the proliferation inhibition rate (PIR) of A549 cells treated with SUF-NPs. Flow cytometry and dual-color fluorescence microscopy were adopted to detect the apoptosis rate. The expression levels of apoptosis-related proteins P53, Bax, and Bcl-2 were detected by Western blot. The results revealed that the average particle size of Suf-NPs was (113.86±2.03) nm, the zeta potential was (−28.44±1.52) mV, the encapsulation efficiency (PER) was (82.02±3.56) %, and the drug loading (DL) capacity was (50.31±6.49) %. As against Con, the PIR, apoptosis rate, P53, and Bax protein expression was significantly higher (P <0.001), and Bcl-2 protein was markedly inferior in Suf, SLN, and Suf-NPs groups (P <0.05). Compared with the Suf, the Suf-NPs group had markedly higher PIR, apoptosis rate, and expression of P53 and Bax proteins (P < 0.05), and markedly lower expression of Bcl-2 protein (P <0.05). Suf-NPs can markedly restrain A549 human LUAD cells, promote their apoptosis, and affect the expression of related genes and proteins. It provides a theoretical basis for the future development of Suf-NPs as a drug for the treatment of lung cancer (LC).

Analysis of the therapeutic efficacy of meloxicam-loaded solid lipid nanoparticles topical gel in Wistar rats knee osteoarthritis

Solid lipid nanoparticles (SLNs) have widely been explored in the topical delivery of drugs across the skin. Lipids in the carrier system fluidize the skin to enhance its permeation which is influenced by several factors including carbon chain length and functional groups. Hence the current study evaluated experimentally the effect of different carbon chain lengths and different functional groups of lipids and formulated as SLNs of meloxicam (MLX-SLNs) on in vitro drug permeability. All the fabricated MLX-SLNs were in the size range of 152 ± 17 nm to 246 ± 5 nm with polydispersity index <0.3. The entrapment efficiency of MLX-SLNs was found to be in the range of 89.13 ± 0.1% to 97.81 ± 0.01%. MLX-SLNs were incorporated into chitosan gel (MLX-SLNs-Gel) and evaluated for flux by performing the ex vivo skin permeation studies. The flux values of SLNs were correlated with the docking reports exhibiting a parabolic relation of lipid chain length with the permeation. Stearylamine SLNs (MLX-SAM-SLNs-Gel) showed the highest flux value of 0.76 ± 0.03 μg/cm2/h. Hence, MLX-SAM-SLNs-Gel was evaluated for monosodium iodoacetate induced osteoarthritis in Wistar rats. The levels of IL-1β (P < 0.001) and TNF-α (P < 0.01) in MLX-SAM-SLNs-Gel treated group were significantly lower as compared to the positive control group and blank SLNs gel group. However, the cytokines levels were comparable to the oral MLX dispersion group owing to no significant (P > 0.05) difference. On the other hand, MLX-SAM-SLNs-Gel was comparable to MLX i.v. solution group in IL-1β levels (P > 0.05) and illuminated significant difference (P < 0.05) in the TNF-α levels. MLX-SAM-SLNs-Gel also demonstrated superior performance in X-ray analysis, histopathology and Osteoarthritis Research Society International scores. In conclusion, topical MLX-SAM-SLNs-Gel may be a potential candidate for translating into a clinically viable product.

Preparation, characterizations and in vitro evaluation of Econazole-Betamethasone loaded solid lipid nanoparticles (SLNs)

Tremendous increase of fungal infections in hospitalized or immune compromised patients has been reported from the last two decades. These infections are commonly treated using econazole and miconazole that have shorter half-life and produce severe side effects. All such issues can be addressed using targeted drug delivery. We developed SNLs based formulation for the treatment of mycosis. The high pressure homogenization method was employed for formulation followed by characterization, assay for antifungal activity, in vitro drug release and ex vivo permeation. The particle size of Econazole-Betamethasone-loaded SLNs, Econazole-loaded SLNs, Betamethasone-loaded SLNs and Blank SLNs were 377.4±23 nm, 298.7±9 nm, 177.7±15 nm and 113.4±6 nm respectively. The SEM images displayed that droplets are uniform and spherical in shape which ranged from 113.4±6 to 377.4±23 nm. In DSC, the SLNs formulation showed endothermic peak at 185.2 °C±0.9. Drug content of Econazole loaded SLNs was 82±0.1 and its entrapment efficiency was approximately 90.4±0.2. Betamethasone SLNs displayed highest drug content which was 83.5±0.4 while encapsulation efficiency of same formulation was 94.2±0.4. The Econazole and Betamethasone combined SLNs exhibited drug content of 80±0.3 while its encapsulation efficiency was 93.1±0.5. E-SLNs have significantly high drug release (p &lt; 0.05) as compared to other formulation B-SLNs and EB-SLNs.The Econazole loaded formulations displayed antifungal activity with no synergistic or antagonistic effect with each other. Drug permeation from Econazole SLNs, Betamethasone SLNs and combined Econazole and Betamethasone SLNs was 45%, 40% and 38% respectively. Overall, SLN’s are an effective carrier for topical delivery of antifungals agents and that may be helpful in bypassing the serious side effects associated with oral delivery.

Protective effect of l-carnitine-loaded solid lipid nanoparticles against H2O2-induced genotoxicity and apoptosis

L-carnitine (LC) is a highly water-soluble compound involved in the β-oxidation of lipids and transportation of long-chain fatty acids across the membrane of mitochondria. However, the higher hydrophilicity of LC limits its free diffusion across the bilayer lipid membrane of intestinal epithelium in oral administration, decreasing oral bioavailability. Drug delivery with nanoparticles enhances cargo bioavailability and cellular uptake and improves therapeutic outcomes while decreasing unwanted side effects. Here, we proposed solid lipid nanoparticles (SLNs) as a hydrophobic carrier for LC delivery, aiming at increasing LC bioavailability and its protective role against intracellular oxidative stress damages. The LC-SLNs were prepared using the hot homogenization technique, and different physicochemical properties were investigated. The inhibition of H2O2-induced ROS generation in human umbilical vein endothelial cells (HUVECs) with plain LC and LC-SLNs was investigated. Moreover, various in vitro experiments were performed to assess whether LC-SLNs can protect HUVECs from H2O2-induced genotoxicity and apoptosis. The monodispersed and spherical blank SLNs and LC-SLNs were 104 ± 1.8 and 128 ± 1.5 nm, respectively with a drug loading (DL) of 11.49 ± 0.78 mg/mL and acceptable encapsulation efficiency (EE%) (69.09 ± 1.12) of LC-SLNs. The formulation process did not affect the antioxidant properties of LC. MTT assay and comet assay demonstrated that the LC-SLNs decreased cytotoxicity and genotoxicity of H2O2, respectively on HUVECs. Besides, LC-SLNs more inhibited ROS generation, along with apoptotic events in H2O2-treated HUVECs compared to the plain LC. Altogether, our findings affirmed the protective effects of LC-SLNs against H2O2-induced genotoxicity and apoptosis in HUVECs. In conclusion, LC-SLN formulation is a promising drug delivery system to overcome the bioavailability issue of hydrophilic LC, enhancing the antioxidant and biological properties of the plain LC.

Glyceryl Monostearate based Solid Lipid Nanoparticles for Controlled Delivery of Docetaxel.

Solid lipid nanoparticles (SLNs) is the drug delivery system that has the capability to improve drug release at the desired tumor site. The aim of the present study is to develop glyceryl monostearate (GMS) based SLNs for the controlled delivery of docetaxel. Hot melt encapsulation (HME) method was employed avoiding the use of organic solvents and, therefore, regarded as green synthesis of SLNs. Optimized DTX-SLNs showed desirable size (100 nm) with low poly dispersity index and excellent entrapment efficiency. Surface charge confirmed the stability of formulation. transmission electron microscope (TEM) analysis showed spherical shaped particles and fourier transform infrared microscopy (FTIR) revealed compatibility among formulation excipients. Differential scanning calorimeter (DSC) analysis revealed that the melting transition peak of optimized formulation was also greater than 40°C indicating that SLNs would be solid at body temperature. In-vitro release profile (68% in 24 hours) revealed the controlled release profile of DTX-SLNs, indicating lipophilic docetaxel drug was entrapped inside high melting point lipid core. Cytotoxicity study revealed that blank SLNs were found to be biocompatible while dose dependent cytotoxicity was shown by DTX-SLNs. These studies suggest that DTX-SLNs have the potential for controlled delivery of docetaxel and improved therapeutic outcome.

Diosmin-loaded solid nanoparticles as nano-antioxidant therapy for management of hepatocellular carcinoma: QbD-based optimization, in vitro and in vivo evaluation

The present work focuses on the development and evaluation of the diosmin-loaded solid lipid nanoparticles (SLNs) with the goal of improving its therapeutic efficacy in hepatic carcinoma (HCC) treatment. HCC was induced by administration of diethyl nitrosamine (DEN) intraperitoneally at a dose of 200 mg/kg in male Wistar rats. The formulation and optimization of diosmin-loaded SLNs was performed using a five-factor and two-level full factorial design. The optimized SLNs exhibited particle size of 37.48 nm, polydispersity index of 0.29 nm, entrapment efficiency of 73.46% and drug loading capacity of 9.075%. In vitro drug release analysis of SLNs performed with dialysis bag technique revealed cumulative drug release >60% in 6 h. In vitro cytotoxicity study of diosmin-SLNs on HepG2 cells showed relatively higher cytotoxicity than diosmin solution and blank SLN. After 48 h of treatment, IC50 values for the diosmin-SLNs and diosmin solution were found to be 22.01 μg/mL and 33.11 μg/mL, respectively. In vivo animal study demonstrated that the hepatic DEN group rats shown hepatic nodules and antioxidant parameters that were altered by the diosmin in a dose-related fashion dramatically (p < 0.001). Diosmin-SLNs demonstrated strongest chemotherapeutic activity against DEN-induced HCC rats over diosmin solution, via the regulation of antioxidant mechanism-induced hepatic parameters. Overall, the studies indicated potential improvement in the biopharmaceutical and anticancer activity of the diosmin loaded in SLNs.

Development and characterization of Brigatinib loaded solid lipid nanoparticles: In-vitro cytotoxicity against human carcinoma A549 lung cell lines

Brigatinib (BG) is a tyrosine kinase receptor inhibitor act as an antineoplastic agent by blocking the action of an abnormal protein that causes cancer cells to multiply. In the current study, nine formulae of BG loaded solid lipid nanoparticles (SLNs) were developed using 32 factorial design. SLNs were prepared by the solvent emulsification technique using stearic acid as lipid and soya- lecithin as a surfactant, both of these act as independent variables, whereas Particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE) and drug loading (DL) were selected as responses. The particle size was found to be in the nano range (176−787 nm), fairly monodisperse (PDI indices 0.19−0.5), interparticle electrical stability was supported by zeta-potential (+1.78 mV to -15.4 mV), whereas EE and DL were in the range of (61.31–87.87 %) (3.35–31.01 %), respectively. Differential scanning calorimetry (DSC) thermograms indicated the amorphous state of BG in the SLN. Fourier transform infrared spectroscopy (FTIR) spectrums confirm non-interaction between drug and polymer while nuclear magnetic resonance (NMR) spectroscopy study revealed BG incorporation in the SLN. A scanning electron microscope (SEM) image exhibit a spherical shape of SLN. The in-vitro release profile demonstrates a sustained release pattern for the selected BS5 SLNs. MTT assay was performed on the optimized SLNs (BS5) and the results are indicative that BG loaded SLN (BS5) showed better cytotoxicity against A349 lung cell lines while compared to BG suspension and blank SLN. Thus, BG loaded SLNs can find Its better place in the non-small cell lung cancer treatment.

Temozolomide-Loaded Solid Lipid Nanoparticles@Hydrogel for Local Treatment of Tumour

Temozolomide (TMZ) is a significant anticancer agent especially for chemotherapy of glioblastoma. In order to reduce the recurrence rate of cancer, in this work an injectable hydrogel composed of TMZ-loaded solid lipid nanoparticles (SLNs) was designed for filling the cavity of a glioblastoma operation. First, TMZ-loaded SLNs (T-SLNs) were prepared by emulsion solvent diffusion and evaporation technology. The optimised formulation showed a particle size of 190.8±15.3nm, a Zeta potential of −20.2±1.7mV, an entrapment efficiency (EE%) of 99.3±0.5%, and drug loading (DL%) of 15.1±2.7%. The optimised formulation was freeze-dried and characterised by scanning electron microscopy (SEM), differential thermogravimetry (DTG), X-ray diffraction (XRD), and stability tests. The freeze-dried T-SLNs were then incorporated into a hydroxypropyl chitosan (HPCS)/diarylaldehyde PEG (PEG-DF) hydrogel bonded with an MRI contrast agent. The hydrogels were evaluated for invitro drug release and cytotoxicity. The results indicated that compared with free TMZ, the T-SLNs@hydrogel prolonged drug release, and both blank SLNs and hydrogel materials did not exhibit cytotoxicity, suggesting the therapeutic efficacy of TMZ was reserved. Thus, comparing with its conventional oral administration, the obtained TMZ-loaded SLNs and the hydrogel could be more potent for local treatment of glioblastoma after an operation.

Implications of Solid Lipid Nanoparticles of Ganoderic Acid for the Treatment and Management of Hepatocellular Carcinoma

The present work describes the systematic development of ganoderic acid (GA)–loaded solid lipid nanoparticles (SLNs) for the treatment of hepatocellular carcinoma (HCC). A full factorial design was employed for optimization of the GA-loaded SLNs prepared by hot-homogenization method, where Capmul MCMC10 and soy lecithin were used as solid lipid and surfactant, while poloxamer 188 was used as stabilizer. GA-SLNs were subjected to detailed in vitro and in vivo characterization studies. The optimized GA-SLNs exhibited particle size of 73 nm, entrapment efficiency of 66% and loading capacity of 11.53%. In vitro drug release study carried out by microdialysis bag method indicated more than 70% drug release was observed within the 8-h time period. In vitro cytotoxicity study of GA-SLNs performed on HepG2 cell line by MTT assay indicated that GA-SLNs exhibited comparatively higher cytotoxicity than GA solution and Blank SLNs. IC50 values of GA-SLNs and GA solution after 72 h exposure were found to be 25.1 μg/mL and 36.2 μg/mL, respectively. Moreover, particle size and amount of GA entrapped in SLNs exhibited nonsignificant difference over a 12-week storage period at 25 °C/75% RH. In vivo anticancer activity of GA-SLNs in male Wistar rats demonstrated significant reduction (P < 0.001) in the size of hepatic nodules and variation in the levels of oxidative stress in a dose-dependent manner. Overall, GA-SLNs showed better chemoprotective effect over GA solution, thus construed superior efficacy of the developed nanoformulation for the treatment of HCC.

Comparison of antiproliferative effect of epigallocatechin gallate when loaded into cationic solid lipid nanoparticles against different cell lines

Several therapeutic properties have been attributed to epigallocatechin gallate (EGCG), a phytopharmaceutical polyphenol with antioxidant and antiproliferative activity. EGCG is, however, very prone to oxidation in aqueous solutions which changes its bioactive properties. Its loading in nanoparticles has been proposed to reduce its degradation while increasing its in vivo efficacy. The aim of this study was to compare the antiproliferative effect of EGCG before and after its loading in solid lipid nanoparticles (SLNs), against five different cell lines (Caco-2, HepG2, MCF-7, SV-80 and Y-79). EGCG produced concentration- and time-dependent antiproliferative effect, with efficacy dependent on the cell line. The order of potency was: MCF-7>SV-80>HepG2>Y-79>Caco-2, for 24 h exposure (MCF-7 IC50=58.60 ± 3.29 µg/mL; Caco-2 IC50>500.00 µg/mL). To the best of our knowledge this is the first study reporting EGCG antiproliferative effect in SV-80 and Y-79 cells. DDAB-SLN physicochemical properties (size ∼134 nm; PI∼0.179; ZP ∼+28mV) were only slightly modified with EGCG loading (EGCG-DDAB-SLN: ∼144 nm; PI∼0.160; ZP ∼+26mV). EGCG loading in SLN, only slightly increases the EGCG antiproliferative effect in MCF-7 and SV-80 cells. SLN exhibited intrinsic toxicity, attributed to the surfactant used in its production. From the obtained results, the biocompatibility of blank SLN must be also considered when testing the efficacy of loaded phytopharmaceutics.

DEVELOPMENT AND EVALUATION OF TIZANIDINE HYDROCHLORIDE LOADED SOLID LIPID NANOPARTICLES

Objectives: The primary objective of the present study is to develop and evaluate tizanidine hydrochloride (TZ) solid lipid nanoparticles (SLNs) using solid lipids/triglycerides.&#x0D; Methods: TZ SLNs were prepared by hot homogenization followed by ultrasonication technique. The prepared SLNs were characterized for drug content, entrapment and loading efficiency, particle size, zeta potential, polydispersity index (PDI), and in intro release kinetics.&#x0D; Results: TZ SLNs were prepared. The particle size ranged from 49.7 to 523.7 nm. PDI of all formulations was good within the range of 0.189–0.487. The zeta potential of blank SLNs was −15.2 mV whereas drug-loaded SLNs showed zeta potential from −8.85 mV to −42.0 mV. Entrapment efficiency observed was in the range of 34.5–75.0%. The cumulative percentage release of TZ from different TZ nanoparticles varied from 35.28% to 83.98% depending on the drug-lipid ratio and the type of lipid and surfactant used. The release kinetic studies of optimized formulation showed that the release was first order and the release mechanism was non-Fickian type.&#x0D; Conclusion: The prepared SLNs were able to sustain the drug release for 24 h, thus reducing dosing frequency and occurrence of side effects, thereby increasing the effectiveness of the drug.

Solid lipid nanoparticles for thermoresponsive targeting: evidence from spectrophotometry, electrochemical, and cytotoxicity studies.

Thermoresponsive drug delivery systems are designed for the controlled and targeted release of therapeutic payload. These systems exploit hyperthermic temperatures (>39°C), which may be applied by some external means or due to an encountered symptom in inflammatory diseases such as cancer and arthritis. The objective of this paper was to provide some solid evidence in support of the hypothesis that solid lipid nanoparticles (SLNs) can be used for thermoresponsive targeting by undergoing solid–liquid phase transition at their melting point (MP). Thermoresponsive lipid mixtures were prepared by mixing solid and liquid natural fatty acids, and their MP was measured by differential scanning calorimetry (DSC). SLNs (MP 39°C) containing 5-fluorouracil (5-FU) were synthesized by hot melt encapsulation method, and were found to have spherical shape (transmission electron microscopy studies), desirable size (<200 nm), and enhanced physicochemical stability (Fourier transform infrared spectroscopy analysis). We observed a sustained release pattern (22%–34%) at 37°C (5 hours). On the other hand, >90% drug was released at 39°C after 5 hours, suggesting that the SLNs show thermoresponsive drug release, thus confirming our hypothesis. Drug release from SLNs at 39°C was similar to oleic acid and linoleic acid nanoemulsions used in this study, which further confirmed that thermoresponsive drug release is due to solid–liquid phase transition. Next, a differential pulse voltammetry-based electrochemical chemical detection method was developed for quick and real-time analysis of 5-FU release, which also confirmed thermoresponsive drug release behavior of SLNs. Blank SLNs were found to be biocompatible with human gingival fibroblast cells, although 5-FU-loaded SLNs showed some cytotoxicity after 24 hours. 5-FU-loaded SLNs showed thermoresponsive cytotoxicity to breast cancer cells (MDA-MB-231) as cytotoxicity was higher at 39°C (cell viability 72%–78%) compared to 37°C (cell viability >90%) within 1 hour. In conclusion, this study presents SLNs as a safe, simple, and effective platform for thermoresponsive targeting.

Determination of all-trans retinoic acid loaded in solid lipid nanoparticles by differential pulse voltammetry at glassy carbon electrode

All- trans retinoic acid (ATRA) is a poorly water-soluble derivate of vitamin A that has been difficult to be parenterally administrated for cancer therapy purposes. Thus, lipid nanocarriers such as solid lipid nanoparticles (SLN) have emerged as an interesting alternative to overcome this drawback of ATRA. In this work, a novel electrochemical method based on differential pulse voltammetry (DPV) to quantify ATRA in SLN is proposed. The scan rate and pulse amplitude were initially optimized and the best values were found to be 30mVs−1 and 75mV, respectively. The influence of pH of the supporting electrolyte on the ATRA oxidation peak was also evaluated and the optimal analysis condition was observed to occur at pH 5.0. No interference of blank SLN or degradation products were observed in the voltammetric ATRA peak and the method was considered to be highly selective for the compound. The method presented adequate linearity in the concentration range of 9.71–45.5×10−6molL−1, with a limit of detection (LOD) and quantification (LOQ) of 1.56×10−6molL−1 and 4.74×10−6molL−1, respectively. The intra-day and inter-days precision showed relative standard deviation lower than 5%. In the accuracy test, the recovery was found in the range of 93.21 to 100.22%. The method was also robust in terms of changes of methanol supplier, but changes in the supporting electrolyte composition and pH of acetate buffer significantly influenced on the method response. Thus, the validated electrochemical DPV method was considered to be highly applicable to the quantification ATRA in SLN.

Toxicity of lidocaine solid lipid nanoparticles in human neurons

Objective To investigate the toxicity of lidocaine solid lipid nanoparticles(SLNs)in human neurons. Methods Lidocaine-loaded SLNs were prepared using high pressure homogenization.SH-SY5Y cells were cultured in vitro and inoculated on 96-well plates(100 μl/well)at a density of 5×105 cells/ml.SH-SY5Y cells were randomized into 10 groups(n=30 each)using a random number table: control group(group C), different concentrations of lidocaine groups(L1-4 groups), different concentrations of lidocaine SLN groups(L-SLN1-4 groups), and blank SLN group(group SLN). The cells were cultured routinely in group C. The cells were incubated with the culture medium containing lidocaine with the final concentrations of 1.000%, 0.500%, 0.250% and 0.125% in L1-4 groups, respectively.In L-SLN1-4 groups, the cells were incubated with the culture medium containing lidocaine SLNs with the final concentrations of 1.000%, 0.500%, 0.250% and 0.125% in L1-4 groups, respectively.Before incubation(at the corresponding time points in group C), and at 1, 12 and 24 h of culture or incubation(T0-3), 6 wells in each group were selected for measurement of the cell survival rate(using methyl thiazolyl tetrazolium assay). The cell morphology was examined with optical microscope at T3. Results Compared with that at T0, the cell survival rate was significantly decreased at each time point in L1-4 and L-SLN1, 2 groups, at T2, 3 in L-SLN3 group, and at T3 in L-SLN4 group(P 0.05). The cell survival rate was significantly lower at T2, 3 in L1-4 and L-SLN1-3 groups, and at T3 in group L-SLN4 than that at T1, and at T3 in L1-4 and L-SLN1-4 groups than that at T2(P 0.05). Compared with group L-SLN at the corresponding concentration, the cell survival rate was significantly decreased at each time point in group L1-4(P<0.05). Conclusion Lidocaine SLNs have toxic effect on human neurons, but the effect is weaker than that caused by lidocaine solution. Key words: Nanocapsules; Lidocaine; Drug toxicity

Delivery of retinoic acid to LNCap human prostate cancer cells using solid lipid nanoparticles

In this study retinoic acid (RTA) loaded solid lipid nanoparticles (SLNs) were optimized by tuning the process parameters (pressure/temperature) and using different lipids to develop nanodispersions with enhanced anticancer activity. The RTA-SLN dispersions were produced by high-pressure homogenization and characterized in terms of particle size, zeta potential, drug entrapment efficiency, stability, transmission electron microscopy (TEM), atomic force microscopy (AFM), X-ray diffraction (XRD) and in vitro drug release. Thermal and X-ray analysis showed the RTA to be in the amorphous state, whilst microscopic images revealed a spherical shape and uniform particle size distribution of the nanoparticles. Anticancer efficiency was evaluated by incubating RTA-SLNs with human prostate cancer (LNCap) cells, which demonstrated reduced cell viability with increased drug concentrations (9.53% at 200ug/ml) while blank SLNs displayed negligible cytotoxicity. The cellular uptake of SLN showed localization within the cytoplasm of cells and flow cytometry analysis indicated an increase in the fraction of cells expressing early apoptotic markers, suggesting that the RTA loaded SLNs are able to induce apoptosis in LNCap cells. The RTA-SLN dispersions have the potential to be used for prostate anticancer treatment.

Improved cytotoxicity of paclitaxel loaded in nanosized lipid carriers by intracellular delivery

Nanosized lipid carriers (NLC) can improve the limited drug-loading (DL) capacity and drug expulsion during storage, and adjust the drug release profile of solid lipid nanoparticles (SLN). In this study, Paclitaxel (PTX)-loaded NLC were prepared by solvent diffusion method using monostearin as solid lipid and oleic acid (OA) as liquid lipid matrix. The blank NLC with different OA content (the size range was from 89.5 ± 7.4 to 160.2 ± 34.6 nm) showed smaller size than the blank SLN (the size was 272.7 ± 43.6 nm), while the PTX-loaded NLC (the size range was from 481.3 ± 29.8 to 561.7 ± 38.3 nm) showed little bigger size, higher DL capacity, and faster drug in vitro release rate comparing with SLN (the size was 437.3 ± 68.2 nm). The 50 % cellular growth inhibitions (IC50) of PTX-loaded NLC with 0, 5, 10, and 20 wt % OA were 0.92 ± 0.06, 0.69 ± 0.04, 0.25 ± 0.02, and 0.12 ± 0.02 µg mL−1, respectively, while the IC50 of TaxolTM was 1.72 ± 0.09 µg mL−1. For analyzing cellular drug effect, cellular uptakes of fluorescent NLC and intracellular drug concentration were investigated. As the incorporation of OA into solid lipid matrix could accelerate both the cellular uptake and the PTX delivery, loaded by NLC, the cytotoxicity of PTX could be enhanced, and further enhanced by increasing OA content in NLC.

Optimization of process variables of zanamivir-loaded solid lipid nanoparticles and the prediction of their cellular transport in Caco-2 cell model

The aim of this study was to optimize the process variables of zanamivir-loaded solid lipid nanoparticles (SLNs) and to predict their cellular transport across Caco-2 cell monolayers. Zanamivir-loaded SLNs were prepared by a double emulsion solvent evaporation method. The effects of process variables on the mean particle size and zeta potential of SLNs were investigated and the physicochemical properties of SLNs were characterized. In addition, the cytotoxicity and transport ability of SLNs were also studied in Caco-2 cell model. The mean particle size of drug-loaded SLNs was significantly affected by the process variables. The SLNs were prepared using glyceryl monosterate (1% polyvinyl alcohol (PVA) or 1.5% poloxamer 188 as surfactant) had a regular shape with a relatively lower mean particle size (324.2 and 224.9nm, respectively), higher encapsulation efficacy (55.7 and 42.4%, respectively) and sustained drug release over 12h. The crystalline form of drug had been partly changed and no physicochemical interaction had occurred between drug and carriers in SLNs. The cell viability was approximately 100% even at a high concentration of blank SLNs. There was no remarkable difference in drug permeation between drug-loaded SLNs and drug solution at 2h, while drug-loaded SLNs showed a significant decrease in drug permeation compared with the drug solution at 4h. The process variables of zanamivir-loaded SLNs were successfully optimized in this study. However, these SLNs significantly reduced the transport ability of zanamivir across Caco-2 cell monolayers. Further studies are needed to fully understand the real absorption mechanism of developed SLNs.

Pharmacokinetics study of arteether loaded solid lipid nanoparticles: An improved oral bioavailability in rats

Arteether (ART), an artemisinin derivative, is a life saving drug for multiple drug resistant malaria. It has a deliverance effect in Falciparum malaria and cerebral malaria. We have prepared solid lipid nanoparticles (SLN) by high pressure homogenization (HPH) technique. ART-loaded SLN (ART-SLN) has been produced reproducibly with homogeneous particle size. ART-SLN was characterized for their size measured by Zetasizer Nano-ZS, Malvern, UK and by high resolution transmission electron microscopy (HR-TEM) and which was found to be 100 ± 11.2 nm. The maximum percentage entrapment efficiency (%EE) determined with the high-performance liquid chromatography (HPLC) has been found to be 69 ± 4.2% in ART-SLN-3. The release pattern from ART-SLN revealed that the release of ART is slow but time-dependent manner, which is desirable as it will help to protect the acid degradation of ART in stomach. The percentage cytotoxicity of blank SLN has been found within the acceptable range. The pharmacokinetics results indicated that ART-SLN-3 absorption has been significantly enhanced in comparison to ART in aqueous suspension and ART in ground nut oil (GNO) in rats. The % relative bioavailability (RB%) of ART-SLN to the ART in GNO and ART in aqueous suspension in rats was 169.99% and 7461%, respectively which was found to be significantly high in both the cases. From the results, it can be concluded that ART-SLN offers a new approach to improve the oral bioavailability of ART.