Surface Of Solid Lipid Nanoparticles Research Articles

Microfluidic assembly of “Turtle-Like” shaped solid lipid nanoparticles for lysozyme delivery

After two decades of research in the field of nanomedicine, nanoscale delivery systems for biologicals are becoming clinically relevant tools. Microfluidic-based fabrication processes are replacing conventional techniques based on precipitation, emulsion, and homogenization. Here, the focus is on solid lipid nanoparticles (SLNs) for the encapsulation and delivery of lysozyme (LZ) as a model biologic. A thorough analysis was conducted to compare conventional versus microfluidic-based production techniques, using a 3D-printed device. The efficiency of the microfluidic technique in producing LZ-loaded SLNs (LZ SLNs) was demonstrated: LZ SLNs were found to have a lower size (158.05 ± 4.86 nm vs 180.21 ± 7.46 nm) and higher encapsulation efficacy (70.15 ± 1.65 % vs 53.58 ± 1.13 %) as compared to particles obtained with conventional methods. Cryo-EM studies highlighted a peculiar turtle-like structure on the surface of LZ SLNs. In vitro studies demonstrated that LZ SLNs were suitable to achieve a sustained release over time (7 days). Enzymatic activity of LZ entrapped into SLNs was challenged on Micrococcus lysodeikticus cultures, confirming the stability and potency of the biologic. This systematic analysis demonstrates that microfluidic production of SLNs can be efficiently used for encapsulation and delivery of complex biological molecules.

Curcumin-Loaded Chitosan Nanoparticle Preparation and Its Protective Effect on Celecoxib-induced Toxicity in Rat isolated Cardiomyocytes and Mitochondria.

Curcumin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory and tissue protective. In here we hypothesized that curcumin-loaded chitosan-coated solid lipid nanoparticles (CuCsSLN) are able to increase its overall bioavailability and hence its antioxidant and mitochondria;/lysosomal protective properties of curcumin. CuCsSLN were prepared using solvent diffusion technique for formation of solid lipid nanoparticles (SLNs) and electrostatic coating of positive-charged chitosan to negative surface of SLNs. CuCsSLN showed the encapsulation efficiency of 91.4±2.7%, the mean particle size of 208±9 nm, the polydispersity index of 0.34±0.07, and the zeta potential of+53.5±3.7 mV. The scanning electron microscope (SEM) images of nanoparticles verified their nanometric size and also spherical shape. Curcumin was released from CuCsSLN in a sustain release pattern up to 24 hours. Then isolated cardiomyocytes and mitochondria were simultaneously treated with (1) control (0.05% ethanol), (2) celecoxib (20 µg/ml) treatment, (3) celecoxib (20 µg/ml)+++CuCsSLN (1 µg/ml) treatment, (4) CuCsSLN (1 µg/ml) treatment, (5) celecoxib (20 µg/ml)+++curcumin (10 µM) treatment and (6) curcumin (10 µM) treatment for 4 h at 37°C. The results showed that celecoxib (20 µg/ml) induced a significant increase in cytotoxicity, reactive oxygen species (ROS) formation, mitochondria membrane potential (ΔΨm) collapse, lipid peroxidation, oxidative stress and mitochondrial swelling while CuCsSLN and curcumin reverted the above toxic effect of celecoxib. Our data indicated that the effect of CuCsSLN in a number of experiments, is significantly better than that of curcumin which shows the role of chitosan nanoparticles in increasing effect of curcumin.

Effects of Chitosan Drug Loaded Nanoparticles on Migration Activity of Retinal Pigment Epithelial Cells

ABSTRACTMethazolamide (MET) was used as a model drug. Chitosan (Chi), which had the advantages of biodegradation, non-toxicity and biocompatibility, was used to modify the surface of solid lipid nanoparticles (SLNs) to construct a stable and targeted drug carrier for eyes. Chi modified MET SLNs were prepared by emulsion evaporation low-temperature curing method. Then, the samples were characterized by infrared spectroscopy and X-ray diffraction. Its effect on hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells was analyzed. Meanwhile, the effect of the prepared nanoparticles (NPs) on the migration of retinal microvascular endothelial cells was analyzed. The results showed that the optimal formulation of Chi modified MET SLNs was as follows: 35 mg MET, 80 mg glyceryl monostearate (GMS), 15 mg phospholipid, and 10 ml anhydrous ethanol, which were heated and dissolved at 80 °C to form an organic phase. Besides, 20 ml solution composed of 1% Tween80 and 2% Polyethylene glycogen (PEG) 400 was used as the internal aqueous phase. Under hypoxia condition, the up-regulation of HIF-1α and VEGF expression was significantly inhibited; the RPE cells treated with prepared NPs migrated to the center, so as to inhibit the migration of vascular endothelial cells. The average inhibition rate was 44%.

Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles.

Background: The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoadhesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuroblastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery.

Targeting Solid Lipid Nanoparticles with Anisamide for Docetaxel Delivery to Prostate Cancer: Preparation, Optimization, and In-vitro Evaluation.

The purpose of the current study was to prepare and characterize the targeted solid lipid nanoparticles (SLNs) containing docetaxel (DTX) for prostate cancer treatment. The goal has been achieved by locating anisamide (Anis) ligand on the surface of SLNs, which can interact with the overexpressed sigma receptor on the prostate cancer cells. DTX loaded SLNs were prepared by high shear homogenization and ultra-sonication method and optimized by applying experimental design. The average particle size and the entrapment efficiency of the optimum DTX-SLN were 174 ± 9.1 nm and 83 ± 3.34%, respectively. The results of differential scanning calorimetry showed that DTX had been dispersed as amorphous in the nanocarriers. Scanning electron microscopy (SEM) images confirmed the nanoscale size and spherical shape of the nanoparticles. The cytotoxicity studies have demonstrated that IC50 of free drug, DTX-SLN and DTX-SLN-Anis was 0.25 ± 0.01, 0.23 ± 0.02, 0.12 ± 0.01 nM on PC3 cell line and 20.9 ± 3.89, 18.74 ± 7.43, and 14.68 ± 5.70 nM on HEK293 cell line, respectively. Targeted DTX-SLN-Anis was acted more effectively on prostate cancer cells in comparison to DTX-SLN and free drug. The results of this study have depicted that the anti-cancer drug loaded in targeted SLNs can be a promising way for cancer treatment. In addition, performing in-vivo studies will be complementary to these findings.

Inhalable solid lipid nanoparticles for intracellular tuberculosis infection therapy: macrophage-targeting and pH-sensitive properties.

Mycobacterium tuberculosis (MTB) is one of the most threatening pathogens for its latent infection in macrophages. The intracellular MTB isolated itself from drugs and could spread via macrophages. Therefore, a mannose-modified macrophage-targeting solid lipid nanoparticle, MAN-IC-SLN, loading the pH-sensitive prodrug of isoniazid (INH), was designed to treat the latent tuberculosis infection. The surface of SLNs was modified by a synthesized 6-octadecylimino-hexane-1,2,3,4,5-pentanol (MAN-SA) to target macrophages, and the modified SLNs showed a higher cell uptake in macrophages (97.2%) than unmodified SLNs (42.4%). The prodrug, isonicotinic acid octylidene-hydrazide (INH-CHO), was synthesized to achieve the pH-sensitive release of INH in macrophages. The INH-CHO-loaded SLNs exhibited a pH-sensitive release profile and accomplished a higher accumulated release in pH5.5 media (82.63 ± 2.12%) compared with the release in pH7.4 media (58.83 ± 3.84%). Mycobacterium smegmatis was used as a substitute for MTB, and the MAN-IC-SLNs showed a fourfold increase of intracellular antibiotic efficacy and enhanced macrophage uptake because of the pH-sensitive degradation of INH-CHO and MAN-SA in SLNs, respectively. For the in vivo antibiotic efficacy test, the SLNs group displayed an 83% decrease of the colony-forming unit while the free INH group only showed a 60% decrease. The study demonstrates that macrophage targeting and pH-sensitive SLNs can be used as a promising platform for the latent tuberculosis infection. Graphical Abstract Table of contents: Macrophage-targeting and pH-sensitive solid lipid nanoparticles (SLN) were administrated to the lung via nebulization. Macrophage targeting was achieved by appropriate particle size and surface mannose modification with synthesized MAN-SA. After being swallowed by macrophages, the prodrug, Isonicotinic acid octylidene-hydrazide (INH-CHO), quickly released isoniazid, which was triggered by the intracellular acid environment. The SLNs exhibited higher intracellular antibiotic efficacy due to their macrophage-targeting and pH-sensitive properties.

Curcumin Containing PEGylated Solid Lipid Nanoparticles for Systemic Administration: A Preliminary Study.

Curcumin (CUR) has a wide range of pharmacological properties, including anti-inflammatory and antioxidant activities, and it can be considered a good candidate for the potential treatment of central nervous system (CNS) pathologies, although its use in clinical practice is compromised due to its high lipophilicity. Solid lipid nanoparticles (SLNs) are well-known nanocarriers representing a consolidated approach for the delivery of lipophilic compounds, but their systemic use is limited due their short half-life. The formulation of stealth SLNs (pSLNs) could be a valid strategy to overcome this limit. Curcumin-loaded-pSLNs were prepared by the solvent evaporation method. Formulation was characterized for their mean size, zeta potential, size distribution, and morphology. Drug antioxidant activity was evaluated by Oxygen Radical Absorbance Capacity (ORAC) assay. Finally, the obtained formulations were analyzed in terms of long-term stability. Curcumin-loaded-pSLNs showed good technological parameters with a mean particle size below 200 nm, as confirmed by TEM images, and a zeta potential value around −30 mV, predicting good long-term stability. Differential Scanning Calorimetry (DSC) analysis confirmed that PEG micelles interacted with the SLN surface; this suggests the location of the PEG on the pSLN surface. Therefore, these preliminary studies suggest that the produced formulation could be regarded as a promising carrier for the systemic administration.

Interfacial and colloidal characterization of oil-in-water emulsions stabilized by interface-tunable solid lipid nanoparticles

We evaluated the correlation between the interfacial characteristics of solid lipid nanoparticles (SLNs) and the interfacial/colloidal stability of SLN-stabilized emulsions. Herein, the interfacial properties of SLNs, particularly the surface load (Γs) of emulsifiers, were tuned by controlling the type/concentration of emulsifier used to prepare the SLNs. Increasing the Γs decreased the contact angle at the oil–water interface, which enhanced the displacement free energy of the SLNs at the interface. Moreover, the Γs of emulsifiers bound to the surface of SLNs covering oil droplets was linearly correlated with the SLN-own Γs. The size/ζ-potential of emulsions stabilized by SLNs covered by the highest concentration of emulsifiers was unchanged for 1 month, indicating good emulsion stability. The interfacial/colloidal stability of SLN-stabilized emulsions was thus enhanced by increasing the emulsifier concentration used to produce the SLNs. This study provides baseline data for developing SLN-stabilized emulsions for the food, cosmetic, and pharmaceutical industries.

Hesperidin-Loaded Solid Lipid Nanoparticles: Development and Physicochemical Properties Evaluation.

Although nanocarrier systems have been investigated to function as therapeutic delivery agents to specific sites of the body, the drug encapsulation method is not always well elucidated. In this work, solid lipid nanoparticles (SLN) composed by stearic acid or cetostearyl alcohol were prepared by a hot homogenization method using poly(vinyl alcohol) or polysorbate as surfactant and loaded with hesperidin, a bioflavonoid that possesses many pharmacological properties. The obtained SLN were characterized by several physicochemical techniques to identify interactions between the constituents and to evaluate the drug incorporation into the nanoparticles. According to scanning electron microscopy and dynamic light scattering the hesperidin-loaded and unloaded SLN have spherical shapes, sizes ranging from 300 to 600 nm, zeta potentials varying from -35 to -20 mV, polydispersity indexes between 0.240 and 0.445, and entrapment efficiencies higher than 88%. X-ray diffraction showed the hesperidin amorphization due to its encapsulation in SLN, and also showed crystallization degree and polymorphic modification of the lipids after the SLN preparation. FTIR, Raman and Photoacoustic spectroscopy revealed no chemical reactions between drug and lipids, however, these results indicated that the drug was incorporated differently into nanoparticles based on the SLN composition. The analysis showed that stearic acid-based SLN prepared with polysorbate were more efficient to enclosure the hesperidin while the glycosydic part of the hesperidin was not entrapped in the cetostearyl alcohol-based SLN; instead, the hesperidin remained on the SLN surface due to lipid crystallization. The physicochemical characterization allowed identifying different types of hesperidin incorporation into the SLN, which can interact in a varied manner as targeted drug delivery systems.

Cost Comparison of Integrative and Complementary Practices Specialized Unit In SUS

CAB51, a compact antibody against human epithelial growth receptor 2 (HER2, ErbB2), has been linked to cationic Solid Lipid Nanoparticles (SLN) via streptavidin-biotin interaction and their targeting potential evaluated against breast cancer cells. The amount of streptavidin and biotinylated antibody was optimised by monitoring the mean complex size (intensity weighed average diameter), polydispersity index and immediate stability in phosphate buffer saline (PBS). The effect on MCF-7 and BT-474 cells was evaluated at concentrations of 0.01 mg/mL and 0.1 mg/mL (counted as solid lipid). Streptavidin adsorption onto SLN surface had no influence on cell viability. Linking the antibody showed a synergistic effect on cell viability at lowest concentration tested (0.01 mg/mL) which was lower than that observed after exposure to SLN alone or antibody alone. At the higher tested concentration (0.1 mg/mL), the observed toxicity was entirely governed by the inherent toxicity of the SLN themselves. Streptavidin adsorption had no effect on accumulation in cells, while the antibody-containing complexes showed clearly increased internalisation in both cell lines. In HER2/neu positive BT-474 higher internalisation was observed than in HER2/neu negative MCF-7.

Surface-tailored anti-HER2/neu-solid lipid nanoparticles for site-specific targeting MCF-7 and BT-474 breast cancer cells

CAB51, a compact antibody against human epithelial growth receptor 2 (HER2, ErbB2), has been linked to cationic Solid Lipid Nanoparticles (SLN) via streptavidin-biotin interaction and their targeting potential evaluated against breast cancer cells. The amount of streptavidin and biotinylated antibody was optimised by monitoring the mean complex size (intensity weighed average diameter), polydispersity index and immediate stability in phosphate buffer saline (PBS). The effect on MCF-7 and BT-474 cells was evaluated at concentrations of 0.01 mg/mL and 0.1 mg/mL (counted as solid lipid). Streptavidin adsorption onto SLN surface had no influence on cell viability. Linking the antibody showed a synergistic effect on cell viability at lowest concentration tested (0.01 mg/mL) which was lower than that observed after exposure to SLN alone or antibody alone. At the higher tested concentration (0.1 mg/mL), the observed toxicity was entirely governed by the inherent toxicity of the SLN themselves. Streptavidin adsorption had no effect on accumulation in cells, while the antibody-containing complexes showed clearly increased internalisation in both cell lines. In HER2/neu positive BT-474 higher internalisation was observed than in HER2/neu negative MCF-7.

Design of multifunctional peptide collaborated and docetaxel loaded lipid nanoparticles for antiglioma therapy

Glioblastoma multiforme (GBM) is one of the most encountered gliomas of the central nervous system. The chemotherapeutic drugs used in the treatment of GBM suffer from poor blood brain barrier penetration, severe systemic toxicities and lack of specificity towards tumor cells. There is an urgent need to explore novel drug delivery systems specifically designed for targeting GBM. Solid lipid nanoparticles (SLN) are biocompatible vehicle with less toxicity issues compared to other drug delivery systems and serve the purpose of obviating the limitations posed by existing anti-cancer drugs for GBM. In this study, angiopep-2, a ligand for the lipoprotein receptor related protein 1 (LRP 1) receptor over expressed in endothelial cells of both brain and glioma, was grafted on the surface of solid lipid nanoparticles for the delivery of docetaxel. The peptide grafted nanoparticles (A-SLN) showed increased cytotoxicity, enhanced cellular internalization and prominent apoptosis than that of unconjugated nanoparticles against U87MG human glioblastoma and GL261 mouse glioma cells. A significant dual targeting effect of A-SLN (p < 0.0001) was confirmed in in-vivo studies by real time fluorescence imaging studies in glioblastoma induced C57BL/6 mice model. Pharmacokinetic and tissue distribution studies showed selective targeting with higher accumulation of A-SLN in brain compared to Taxtotere, a marketed formulation of docetaxel. After treatment with A-SLN, the mean animal survival time of the animals was significantly enhanced to 39 days from 24 days of plain docetaxel. Collectively, this study indicated that solid lipid nanoparticles decorated with angiopep-2 can be an excellent option as targeted drug delivery system for antiglioma therapy.

Optimization of linalool-loaded solid lipid nanoparticles using experimental factorial design and long-term stability studies with a new centrifugal sedimentation method

Linalool (C10H18O), also known as 3, 7-dimethyl-1, 6-octadien-3-ol, is the most common acyclic monoterpene tertiary alcohol present in essential oils of several aromatic plant species. Previous studies indicate that linalool is a valuable compound with a wide range of therapeutic properties. The promising therapeutic effects of linalool are however limited by its poor water solubility and volatility. Recently, the encapsulation of linalool in drug delivery systems, such as solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) has demonstrated to overcome linalool physicochemical limitations. The present study aimed the production and optimization of linalool encapsulation in SLN applying the experimental full factorial design. The estimation of the long-term stability of the produced linalool-loaded SLN was carried out using a new centrifugal sedimentation method, LUMiSizer®. SLN dispersions were produced by the hot high pressure homogenization (HPH) method. The influence of the independent variables, surfactant and lipid concentrations on linalool-loaded SLN particle size, polydispersity index (PI) and zeta potential (ZP) was evaluated by a 22 factorial design composed of 2 variables which were set at 2-levels each. For each of the three dependent variables, analysis of the variance (ANOVA) was performed using a 95% confidence interval. The concentration of surfactant, as well as, the interaction between the different concentrations of lipid and surfactant, hada statistically significant effect on the particle size and PI. Experimental factorial design has been successfully employed to develop an optimal SLN dispersion, requiring a minimum of performed experiments. Based on the obtained results, the optimal linalool-loaded SLN dispersion was composed of 1% (w/v) linalool 2% (w/v) of solid lipid and 5% (w/v) of surfactant. Furthermore, the stability analysis revealed that the produced linalool-loaded SLN dispersions have limited storage stability which can be easily overcome through the assembly of a polymeric coating on the SLN surface. LUMiSizer® has been successfully used in the kinetic analysis of linalool-SLN during accelerated storage time.

Solid lipid-polymer hybrid nanoparticles prepared with natural biomaterials: A new platform for oral delivery of lipophilic bioactives

In this study, an innovative oral delivery system, solid lipid-polymer hybrid nanoparticles (SLPN), was prepared from all-natural biomaterials without use of synthetic surfactants, toxic chemicals, or organic solvents. SLPN were comprised of three components, solid lipid nanoparticles (SLN) as the inner core, bovine serum albumin (BSA)-dextran (BD) conjugate obtained through Maillard reaction as natural emulsifier anchored on the surface of SLN, and pectin as the secondary polymeric coating. Six types of solid lipids, including two glycerides and four saturated fatty acids, were comprehensively tested for their applicability to prepare SLN core and their compatibility with polymeric shells to form SLPN. SLPN prepared with glycerides exhibited superior colloidal properties, including smaller particle size, narrower size distribution, and better stability under simulated gastrointestinal fluids, compared to those prepared with fatty acids. Hydrophobic interactions were the driving force to form SLPN with BD conjugate, while pectin coating afforded greater surface hydrophilicity responsible for exceptional colloidal stability under gastrointestinal conditions. SLPN demonstrated high encapsulation efficiency and controlled release of curcumin, with glycerides as lipid core being more desirable than those prepared with fatty acids. Fluorescence microscope images revealed that encapsulation in SLPN significantly facilitated cellular uptake of curcumin by Caco-2 cells without any cytotoxicity. Collectively, this study provides a promising strategy to develop safe and effective oral delivery platform for lipophilic bioactives, which may open new avenues in functional foods.

Control of the gastrointestinal digestion of solid lipid nanoparticles using PEGylated emulsifiers

We prepared solid lipid nanoparticles (SLNs) with tristearin and various emulsifiers which had different chain length PEGs (10–100 times-repetition of ethylene glycol) to control their digestion fate in the gastrointestinal tract. Fabricated SLNs after acidic/high-ionic-strength media treatment were stable regardless of the ζ-potential (ZP) disappearance. Additionally, highly PEGylated SLNs successfully hindered the adsorption of both bile acid (BA) and lipase on the SLN surface, while lowly PEGylated SLNs interrupted that of only lipase. In simulated small intestinal fluid, lipolysis of highly PEGylated SLNs increased with decrease of the emulsifier density on the SLNs, whereas lipolysis of lowly PEGylated SLNs increased with decrease of the particle size. These results suggested that high PEGylation was more efficient than low PEGylation to hinder the lipolysis initiated from the competitive replacement of the SLN-covering emulsifiers with BAs. Consequently, the SLN digestion could be controlled by choosing the length and concentration of PEGylated emulsifiers.

Solid lipid nanoparticles surface modified with anti-Contactin-2 or anti-Neurofascin for brain-targeted delivery of medicines

Multiple sclerosis (MS) is a chronic central nervous system (CNS) inflammation. Efficient drug delivery to brain is however hampered by blood–brain barrier (BBB). In order to have highly efficient and safe delivery of drugs to brain, solid lipid nanoparticles (SLNs) have indicated promising potentials as smart carriers that can pass the blood–brain barrier and deliver therapeutic biomolecules to the brain. In this study, PEGylated SLNs surface modified using anti-Contactin-2 or anti-Neurofascin, two axo-glial-glycoprotein antigens located in node of Ranvier, were prepared. These targeting moieties are considered as the main targets of autoimmune reaction in MS. The targeted SLNs were then characterized and their in vitro release profile together with their cell viability and uptake were studied. Their brain uptakes were also probed following injections in MS-induced mice. It was found that the targeted PEGylated SLNs had no significant cytotoxicity on U87MG cells although their cellular uptake was increased 4- and 8-fold when surface modified with anti-Contactin-2 or anti-Neurofascin, respectively, compared to control. Brain uptake results demonstrated higher uptake of surface-modified SLNs in the brain tissue compared with the PEGylated SLNs. The results of this report will help scientist to design more efficient nanocarriers for treatment of MS.

ApoE-modified solid lipid nanoparticles: A feasible strategy to cross the blood-brain barrier

Solid lipid nanoparticles (SLN) are colloidal drug delivery systems characterized by higher entrapment efficiency, good scalability of the preparation process and increased sustained prolonged release of the payload compared to other nanocarriers. The possibility to functionalize the surface of SLN with ligands to achieve a site specific targeting makes them attractive to overcome the limited blood-brain barrier (BBB) penetration of therapeutic compounds. SLN are prepared for brain targeting by exploiting the adaptability of warm microemulsion process for the covalent surface modification with an Apolipoprotein E-derived peptide (SLN-mApoE). Furthermore, the influence of the administration route on SLN-mApoE brain bioavailability is here evaluated. SLN-mApoE are able to cross intact a BBB in vitro model. The pulmonary administration of SLN-mApoE is related to a higher confinement in the brain of Balb/c mice compared to the intravenous and intraperitoneal administration routes, without inducing any acute inflammatory reaction in the lungs. These results promote the pulmonary administration of brain-targeted SLN as a feasible strategy for improving brain delivery of therapeutics.

Preparation and investigation of solid lipid nanoparticles for drug delivery

Solid lipid nanoparticles (SLN), a promising drug delivery vehicle, offer an alternative system to traditional colloidal carriers. In our study 12 new SLN formulations were fabricated via the “microemulsion (ME) method”, each leading to a different SLN size and composition. This method is a relatively easy technique and involves biocompatible conditions. Stearic acid has been used as lipid material of which the ratio is kept under 4% to prevent particle growth. Particle size and surface properties of the synthesized SLNs were controlled using various combinations of emulsifiers such as lithocholic acid, Pluronic F127, Tween 20, lecithin and butanol. Furthermore, the mean size of the particles was adjusted by changing the ME:water ratio in the dilution step which is independent from composition. It was found that most of the SLNs were in the colloidal size range (below 100nm) and spherical in shape, which provides high surface area to exploit, as an alternative adsorptive drug carrier system. Also, the surface charge density values of SLNs were calculated by considering size and zeta potential values which then helps in understanding the surface potential of particles. MB was chosen as a model molecule and entrapped on the surface of SLNs after the preparation, to determine the loading capacities and release efficiencies. As such, SLNs have been successfully produced which have controllable drug entrapment efficiency and release capacity according to the chosen combination of emulsifiers and dilution ratio. Thus, this study contributes to the improvement of alternative drug delivery systems with biocompatible and stable newly formulated SLNs.

Modification and stabilizing effects of PEG on resveratrol-loaded solid lipid nanoparticles

Resveratrol-loaded solid lipid nanoparticles (SLNs) modified by polyethylene glycol (PEG2000) (RES–PEG–SLNs) were prepared to study the stabilizing influences of PEG2000 on SLNs properties including loading capacity, particle size, photostability, and release. The micromorphology, particle size distribution, drug–lipid–modifier interaction and crystalline structure were characterized to elucidate stabilizing effects of PEG2000 on SLNs. Compared with ordinary SLNs, SLNs modified by PEG2000 at relatively low amounts of [m(PEG2000):m(lipids) = 1:10] exhibit high drug loading, steady nanoparticle size distributions, photostability and sustained release. According to characterizations, RES–PEG–SLNs formation is dependent on the physical interactions of drug–lipid–modifier. Since PEG2000 is doped into lipid matrix in a non-crystalline state, the lipids crystalline arrangement is disrupted. Additionally, RES–PEG–SLNs are crystallized in a PEG2000/lipid eutectic mixture rather than a simple mixture, inhibiting the lipid polymorphism transformation from α- to β-form, and therefore preventing drug exclusion from the lipid matrix. The PEG2000/lipid matrix contains lattice defects, which allow for the incorporation of more resveratrol and preventing it from photodegradation effectively. In contrast to the burst release of SLNs modified without PEG2000, resveratrol is released more slowly from the lattice defects in lipid matrix of RES–PEG–SLNs, resulting in a sustained release fitted by a two-stage exponential kinetic equation. PEG2000 is distributed on the RES–PEG–SLNs surface, increasing repulsion between nanoparticles and avoiding particles aggregation. These results confirm that both matrix doping effects and surface steric hindrance produced by the presence of PEG2000 play important roles in maintaining high loadings, nanoparticle size, photostability and sustained release.

Conjugation of melanotransferrin antibody on solid lipid nanoparticles for mediating brain cancer malignancy.

Solid lipid nanoparticles (SLNs) comprising complex internal lipids were conjugated with melanotransferrin antibody (MA) to carry anticancer etoposide across the blood-brain barrier (BBB) for managing glioblastoma multiforme (GBM). MA was crosslinked on the surface of etoposide-loaded SLNs (ETP-SLNs) to target human brain-microvascular endothelial cells (HBMECs) and U87MG cells. The experimental evidences showed that an increase in the tripalmitin weight percentage in lipids enhanced the particle size and viability of U87MG cells, however decreased the etoposide loading efficiency, MA conjugation efficiency, and permeability coefficient for etoposide across the BBB. A high level of MA on the particle surface increased the atomic ratio of nitrogen to phosphorus and permeability coefficient for propidium iodide and etoposide across the BBB, however reduced the MA conjugation efficiency, transendothelial electrical resistance, and viability of U87MG cells. Based on immunochemical staining, we found that MA on ETP-SLNs triggered the melanotransferrin-mediated transcytosis and promoted the growth-inhibitory efficacy to U87MG cells. MA-conjugated ETP-SLNs can be a promising colloidal delivery system for malignant GBM pharmacotherapy. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 32:480-490, 2016.