Types Of Solid Lipid Nanoparticles Research Articles

Fabrication of edible solid lipid nanoparticle from beeswax/propolis wax by spontaneous emulsification: Optimization, characterization and stability

In the current study, the production and characterization of novel solid lipid nanoparticles (SLNs) using safe/low-cost natural beeswax (BW) and propolis wax (PW) and by the simple and inexpensive assay of spontaneous emulsification were studied. To fabricate SLNs, the optimum levels of surfactant/oil ratio (SOR), stirring speed, and time were obtained based on minimum particle size (PS) and polydispersity index (PDI). Therefore, the optimal conditions to produce PW and BW nanoparticles were SOR of 1.26 and 2 under stirring speed of 1050 rpm for 20 min, leading to PS of 21.9 and 23.2 nm, respectively. The contact angle of 73.7° and 62.9° for BW and PW SLNs respectively, showed suitable hydrophilicity to stabilize oil-in-water (O/W) Pickering emulsions. Temperatures over 70 °C led to a drastic increment of PS in both types of SLNs. Upon nanoparticles drying, the utilization of cryoprotectants could cause less aggregation and better reconstitution.

Solid lipid nanoparticles made of trehalose monooleate for cyclosporin-A topic release

The aim of this work was the preparation of solid lipid nanoparticles, based on trehalose monooleate, loaded with cyclosporin-A for potential treatment of psoriasis. Trehalose was esterified with oleic acid in order to obtain a more lipophilic compound suitable as a lipid matrix for the formulation of a new type of solid lipid nanoparticles. The ester formation was confirmed by FT-IR and 1HNMR. The solid lipid nanoparticles, based on trehalose monooleate, were successfully prepared with and without cyclosporin-A, using the microemulsion technique. Further characterizations were performed by differential scanning calorimetry (DSC). The drug release from the SLNs was then evaluated through the Franz diffusion cells, using both dialysis membranes and rabbit ear skin. With the aim to verify the localization of SLNs in the skin layers, additional investigations using confocal microscope and stripping tape test were carried out. Finally, a dermatological formulation, based of SLNs loaded with cyclosporin-A, was prepared and tested through Franz diffusion cells. The obtained results indicate the possibility of using these nanoparticles as vehicle of cyclosporin-A for topical treatment of psoriasis, reducing the side effects due to systemic absorption of cyclosporin-A and, at the same time, increasing its concentration at skin injury level.

Possibilities in the application of solid lipid nanoparticles in combination with 5-fluorouracil to overcome the drugresistance of non-small cell lung cancer cell line A549

Introduction: Multidrug resistance of non-small cell lung cancer cells is associated with a high percentage of therapeutic failures. The aim of this study was to assess the ability of solid lipid nanoparticles as a transporter of the conventionally used cytostatic (5-fluorouracil) to overcome the resistance of A549 cells. Material and methods: MTT assay was used to assess the differences in viability of cells treated with 5-fluorouracil alone or in combination with different types of solid lipid nanoparticles. Type of cell death and distribution of cell cycle phases were evaluated using flow cytometry. Results: The use of nanoparticles as a 5-fluorouracil transporter reduced the viability of A549 cells to a greater extent than the cytostatic alone. This was mainly due to the increase in apoptosis, but also necrosis and cell cycle arrest. Conclusion: Our results indicate the great potential of nanotechnology in the treatment of non-small cell lung cancer. By using nanoparticles, it is possible to sensitise tumour cells to cytostatics to which they are normally resistant. In addition, literature data confirm the safety of solid lipid nanoparticle application.

Solid lipid nanoparticles affect microbial colonization and enzymatic activity throughout the decomposition of alder leaves in freshwater microcosms

Solid lipid nanoparticles (SLNs) are used as carriers for drug delivery, and are high biocompatible and designed to endure in the host organism. Despite its current industrial production is low, many of these substances are available on the market, and much more are in the production pipeline. As a result, many of them will end in aquatic systems raising the question whether they can pose a risk to aquatic biota and the associated ecological processes. Microbial decomposers of plant litter, play a key role in forested streams being responsible for the energy flow between terrestrial and aquatic environments. Here, we investigated the effects of SLNs on alder leaf litter decomposition by aquatic microbes. Alder leaves were immersed in a stream of Northeast Portugal to allow microbial colonization before being exposed in microcosms of two types of SLNs at two concentrations for 42 days. Results showed that rates of leaf decomposition decreased with exposure to SLNs. Bacterial biomass was not inhibited by SLNs, and cultivable fungi densities remained constant (SLN-A) or increased (SLN-C) compared with control microcosms. The type and concentration of SLNs influenced differently the leaf colonization by fungi as well as fungal sporulation rate. These effects were accompanied by changes in the community extraenzymatic profile: the activities of alkaline phosphatase, acidic phosphatase, Naphthol-AS-BI-phosphohydrolase (P cycle) and lipases increased in the SLNs microcosms. This study provided the first evidence of the adverse effects of the release of SLNs to streams on leaf litter decomposition. Those effects seem to depend on the composition and concentration of SLNs, as well on the microbial target group, or enzyme. Thus, prior to massive industrial production of these nanomaterials, some measures should be taken to avoid environmental impact affecting the microbial communities responsible for detritus decomposition.

Tissue distribution of borneol-modified ganciclovir-loaded solid lipid nanoparticles in mice after intravenous administration

The main purpose of this research was to prepare borneol-modified and non-borneol ganciclovir-loaded solid lipid nanoparticles (SLNs) to study whether borneol could enhance the transport of ganciclovir (GCV) incorporated in SLN to the brain in mice after their intravenous administration. Ganciclovir injection (GCV-inj) was selected as a control. The SLNs were prepared using a modified microemulsion method. Pharmacokinetic and biodistribution studies were conducted in kunming mice after intravenous administration of GCV-inj, GCV solid lipid nanoparticles without borneol (GCV-SLN), and three types of GCV solid lipid nanoparticles containing different ratios of borneol (GCVb-SLN). It was found that, in plasma, the area under the concentration–time curve (AUC0∼t) for GCVb-SLN and GCV-SLN was greater than that for the GCV-inj. In the brain, the AUC0∼t of GCVb-SLN was significantly increased compared with that of a GCV-inj and GCV-SLN. In the other mouse tissues, the peak concentration of GCV achieved was always lower after the injection of any of the four types of SLN than after the commercial injection. These results indicate that GCV-SLN modified with borneol enhances the transport of ganciclovir to the brain. Therefore, SLN modified with borneol is a potential delivery system for transporting drugs to the central nervous system (CNS).

Idebenone-loaded solid lipid nanoparticles for drug delivery to the skin: In vitro evaluation

Idebenone (IDE), a synthetic derivative of ubiquinone, shows a potent antioxidant activity that could be beneficial in the treatment of skin oxidative damages. In this work, the feasibility of targeting IDE into the upper layers of the skin by topical application of IDE-loaded solid lipid nanoparticles (SLN) was evaluated. SLN loading different amounts of IDE were prepared by the phase inversion temperature method using cetyl palmitate as solid lipid and three different non-ionic surfactants: ceteth-20, isoceteth-20 and oleth-20. All IDE loaded SLN showed a mean particle size in the range of 30–49nm and a single peak in size distribution. In vitro permeation/penetration experiments were performed on pig skin using Franz-type diffusion cells. IDE penetration into the different skin layers depended on the type of SLN used while no IDE permeation occurred from all the SLN under investigation. The highest IDE content was found in the epidermis when SLN contained ceteth-20 or isoceteth-20 as surfactant while IDE distribution into the upper skin layers depended on the amount of IDE loaded when oleth-20 was used as surfactant. These results suggest that the SLN tested could be an interesting carrier for IDE targeting to the upper skin layers.

Characterization and Stability of Nanostructured Lipid Carriers as Drug Delivery System

Recently more focus has been put to the development of innovative drug-delivery systems that includes polymer nanoparticles, emulsions and liposomes and solid lipid nanoparticles (SLNs). The SLNs have been proposed to be an alternative colloidal drug delivery system. The aim of this study was preparation and characterization of solid lipid nanoparticle (SLN) using varieties of emulsifier for encapsulation of the drug with poor water solubility. In these study four types of solid lipid nanoparticles were prepared based on different compositions of palm oil (S154) and lecithin (Lipoid 100) using the high pressure homogenization method. The SLN formulation had the following (palm oil+lecithin) compositions: SLN-01 (90 + 10%, respectively), SLN-02 (80 + 20%, respectively), SLN-03 (70 + 30%, respectively) and SLN-04 (60 + 40%, respectively). The SLNs were characterized and the optimum stability factors for one year storage determined. The parameters used to characterize the SLNs were particle size and polydispersity index (particle sizer), zeta potential (zetasizer), crystallinity (differential scanning calorimetry and wide angle X-ray diffraction), ultrastructure (transmission electron microscopy). Varying the palm oil and lecithin compositions resulted in SLNs of variable sizes and zeta potentials. The particle sizes of SLN-01, SLN-02, SLN-03 and SLN-04 were 298.40 +/- 11.80, 255.40 +/- 3.20, 145.00 +/- 3.39 and 273.00 +/- 86.50 nm, respectively, while the zeta potentials were -19.44 +/- 60.00, -19.50 +/- 1.80, -17.83 +/- 10.00 and -13.33 +/- 2.30 mV, respectively. Thermoanalysis and X-ray diffraction analysis showed that the SLNs had lower crystallinity than bulk lipid. The SLNs were generally round and uniform in shape under transmission electron microscopy. The SLN dimensional data suggested they had high quality physicochemical characteristics, which are conducive for the loading of poor water solubility drugs.

Development of nanoparticle-based magnetic resonance colonography

This study was to develop a novel method of nanoparticle-based MR colonography. Two types of solid lipid nanoparticles (SLNs) were synthesized with loading of (a) gadolinium (Gd) diethylenetriaminepenta acetic acid to construct Gd-SLNs as an MR T1 contrast agent and (b) otcadecylamine-fluorescein-isothiocyanate to construct Gd-fluorescein isothiocyanate (FITC)-SLNs for histologic confirmation of MR findings. Through an in vitro experiment, we first evaluated the size distribution and gadolinium diethylenetriaminepenta acetic acid entrapment efficiency of these SLNs. The SLNs displayed a size distribution of 50-300 nm and a gadolinium diethylenetriaminepenta acetic acid entrapment efficiency of 56%. For in vivo validation, 30 mice were divided into five groups, each of which was administered a transrectal enema using: (i) Gd-SLNs (n=6); (ii) Gd-FITC-SLNs (n=6); (iii) blank SLNs (n=6); (iv) gadolinium diethylenetriaminepenta acetic acid (n=6); and (v) water (n=6). T1-weighted fluid-attenuated inversion-recovery MRI was then performed on mice after transrectal infusion of Gd-SLNs or Gd-FITC-SLNs, which demonstrated bright enhancement of the colonic walls, with decrease in T1 relaxation time. When Gd-FITC-SLNs were delivered, green fluorescent spots were visualized in both the extracelluar space and the cytoplasm through colonic walls under confocal microscopy and fluorescence microscopy. This study establishes the "proof-of-principle" of a new imaging technique, called "nanoparticle-based MR colonography," which may provide a useful imaging tool for the diagnosis of colorectal diseases.

Preparation and Cytotoxicity of Imiquimod-Loaded Solid Lipid Nanoparticles

Based on the experience with pure hard fats SLN, a new type of solid lipid nanoparticles (SLN) has been developed by mixturing monoglyceride with semisolid lipid. Imiquimod, as a water-insoluble drug model, was incorporated into SLN (IMQD-SLN). Particle size measured by photo correlation spectroscope (PCS) was found to be 133±6 nm with a polydispersity index 0.348±0.05. Differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies were performed to explore the state of lipid modification and drug. The cytotoxicity of SLN was researched by MTT method. DSC and PXRD analysis showed that imiquimod was dispersed in SLN in an amorphous state. No cytotoxicity which could suggest that IMQD-SLNs have no irritation to skin was found in MTT experiment. It could be concluded that the IMQD-SLN might be a promiseful transdermal delivery system for imiquimod.

Duodenal administration of solid lipid nanoparticles loaded with different percentages of tobramycin

Three types of solid lipid nanoparticles (SLN) containing three different percentages of tobramycin (1.25, 2.50, 5.00%) were prepared (Tobra-SLN), and the in vitro tobramycin diffusion through a hydrophilic/lipophilic membrane was determined. A variable quantity of each of the three SLN types was placed in the donor compartment to achieve the same amount of tobramycin in each case. Tobramycin diffusion varied with the percentage of drug incorporated in SLN: the higher the percentage of tobramycin incorporated, the greater the amount of the drug diffused. In vivo uptake and transport were determined after administering a fixed dose of tobramycin (5mg/kg) in each of the three types of SLN intraduodenally to rats. At fixed times, blood was sampled from the jugular vein and lymph from the thoracic duct. Lymph and blood were examined by transmission electron microscopy (TEM) analysis to detect the presence, sizes, and shape of SLN. The pharmacokinetic parameters varied considerably with the type of Tobra-SLN: the area under the curve of plasma concentration versus time (AUC) of 1.25% Tobra-SLN was more than five times higher than that of 5.00% Tobra-SLN; the longest residence time was obtained with 1.25% Tobra-SLN; and the clearence of 5.00% Tobra-SLN was fivefold than that of 1.25% Tobra-SLN. This behavior may be related to the differences among the three types of SLN; namely, the number of SLN administered and the mean diameter, the total surface area, and the drug content in each nanoparticle. TEM analysis showed that Tobra-SLNs were targeted to the lymph. Tobra-SLN may act as a reservoir of the drug in the lymphatic system, thereby favoring its sustained release.

Intravenous Administration to Rabbits of Non-stealth and Stealth Doxorubicin-loaded Solid Lipid Nanoparticles at Increasing Concentrations of Stealth Agent: Pharmacokinetics and Distribution of Doxorubicin in Brain and Other Tissues

The pharmacokinetics and tissue distribution of doxorubicin incorporated in non-stealth solid lipid nanoparticles (SLN) and in stealth solid lipid nanoparticles (SSLN) (three formulations at increasing concentrations of stearic acid-PEG 2000 as stealth agent) after intravenous administration to conscious rabbits have been studied. The control was the commercial doxorubicin solution. The experiments lasted 6 h and blood samples were collected at fixed times after the injections. In all samples, the concentration of doxorubicin and doxorubicinol were determined. Doxorubicin AUC increased as a function of the amount of stealth agent present in the SLN. Doxorubicin was still present in the blood 6 h after the injection of SLN or SSLN, while no doxorubicin was detectable after the i.v. injection of doxorubicin solution. Tissue distribution of doxorubicin was determined 30 min, 2 and 6 h after the administration of the five formulations. Doxorubicin was present in the brain only after the SLN administration. The increase in the stealth agent affected the doxorubicin transported into the brain; 6 h after injection, doxorubicin was detectable in the brain only with the SSLN at the highest amount of stealth agent. In the other rabbit tissues (liver, lungs, spleeen, heart and kidneys) the amount of doxorubicin present was always lower after the injection of any of the four types of SLN than after the commercial solution. In particular, all SLN formulations significantly decreased heart and liver concentrations of doxorubicin.

Characterisation of a novel solid lipid nanoparticle carrier system based on binary mixtures of liquid and solid lipids

A drug carrier of colloidal lipid particles with improved payloads and enhanced storage stability was investigated. Based on the experiences with hard fats nanoparticles, a new type of solid lipid nanoparticles (SLN) has been developed by incorporating triglyceride containing oils in the solid core of said particle. The structure and mixing behaviour of these particles were characterised and practical implications on controlled release properties tested. Nanoparticles were characterised by their melting and recrystallisation behaviour as recorded by differential scanning calorimetry (DSC). Polymorphic form and bilayer arrangement were assigned by wide-angle X-ray scattering (WAXS) and small-angle X-ray scattering (SAXS). Size distribution and storage stability were investigated by laser diffractometry (LD). Release properties were studied by drug release model according to Franz. A medium chain triglyceride oil was incorporated successfully in a matrix of a solid long chain glyceride. The crystal order was greatly disturbed, however, the carrier remained solid. The oil inside the particle remained in a liquid state and induced a slight shift form the β′ polymorph to the β i form. Long spacings varied within 0.1 nm with increasing oil loads. Nanoparticles with low oil concentrations showed sustained release properties. Improved drug load levels were encapsulated by lipid particles supplemented with oily constituents. Thus, the presented carrier adds additional benefits to the well-known opportunities of conventional SLN and is suited for topical use.

Solid lipid nanoparticles as carriers of hydrocortisone and progesterone complexes with β-cyclodextrins

Inclusion complexes of hydrocortisone and progesterone were formed with β-cyclodextrin or 2-hydroxypropyl-β-cyclodextrin. The formation of the complexes was confirmed by differential scanning calorimetry (DSC). The inclusion complexes were incorporated in two types of solid lipid nanoparticles (SLN). In the presence of the complexes the sizes of SLN remained below 100 nm. DSC analysis showed that hydrocortisone and progesterone are dispersed in SLN in an amorphous state. Using the β-cyclodextrin complexes the incorporation of the more hydrophilic drug, hydrocortisone, was higher than that of progesterone. Release of hydrocortisone and progesterone from SLN was lower when they were incorporated as inclusion complexes than as free molecules.