Stable Nanostructured Lipid Carriers Research Articles

Effect of surfactant concentration and solidification temperature on the characteristics and stability of nanostructured lipid carrier (NLC) prepared from rambutan (Nephelium lappaceum L.) kernel fat

Nanostructured lipid carrier (NLC) was fabricated from rambutan (Nephelium lappaceum L.) kernel fat stabilized with Tween 80 in this present work. The influence of the Tween 80 concentration (0.025, 0.05, 0.1, 0.2, 0.5 and 1.0wt%) and solidification temperature (5 and 25°C) on the characteristics and stability of the NLC were investigated. The results showed that an increase in the Tween 80 concentration caused decreased zeta-potential (ζ-potential) and particle size (Z-average) with no significant effect on the polydispersity index (PDI). Lipid particles in the NLC at all Tween 80 concentrations had a tendency to grow and the PDI tended to increase due to Ostwald ripening upon storage over 28days. At least 0.2wt% Tween 80 concentrations could be used to stabilize 1wt% rambutan NLC. The solidification temperature affected the microstructure, melting behavior and stability of rambutan NLC. Pre-solidification at 5°C could create stable NLC with monodispersed-spherical lipid particles. Consequently, these stable NLC particles produced from rambutan kernel fat may serve as useful carriers for the delivery of bioactive lipophilic nutraceuticals.

Tacrolimus-loaded nanostructured lipid carriers for oral delivery – Optimization of production and characterization

Tacrolimus (TL), which is currently the mainstay of immunosuppressive therapy faces significant hurdles subsequent to its oral administration attributable to its poor aqueous solubility and extensive intestinal and hepatic first pass metabolism. Therefore, the present study aimed to design the stable nanostructured lipid carrier (NLC) of TL that would be able to overcome such hurdles. Capmul MCMC8 and Compritol 888ATO in 3:2 were selected as binary lipid phase on the basis of solubility study. An exhaustive screening of surfactants is done by aqueous titration to select the surfactant with best emulsifying potential and to optimize the concentration of lipids and surfactants in NLC. Different methods of preparation were explored and compared to optimize NLC which could have the best characteristic properties. TL-NLC was characterized for particle size, drug entrapment efficiency, crystal state, surface morphology and drug release. The obtained particle size, PDI and % drug entrapment efficiency of optimized formulations i.e., NLC-C2 and NLC-N2 were 70±5.42nm, 98±7.52nm; 0.43±0.081, 0.2±0.029 and 87±2.34%, 94±3.18%, respectively. The results of in vitro release studies showed significantly increased (***p<0.001) and sustained release of TL from NLC dispersions as compared to drug suspension (95.73% from NLC-C2, 99.86% from NLC-N2 and 9.27% drug suspension in pH 1.2 in 24h; 93.11% from NLC-C2, 96.65% from NLC-N2 and 10.2% drug suspension in pH 6.8 in 24h). The study demonstrated that proper selection of excipients (by aqueous titration) and modification of method of preparation (by inclusion of cold step) would lead to production of NLC with best characteristic properties.

α-Tocopherol을 함유한 Nanostructured Lipid Carriers의 특성과 안정화 효과

Loading of hydrophobic α-tocopherol into nanostructured lipid carrier (NLC) was performed for improving its oxidative stability. First, various NLCs with different constituents and mixing ratios were prepared and their characteristics were investigated. While the stable NLCs were made when cetyl palmitate (CP) or glyceryl monosterate (GMS) was used as a solid lipid, the phase separation occurred in the NLCs consisting of stearic acid. Particle sizes of the NLCs were several hundreds of nanometers and the size decreased with increasing the ratio of solvent to lipid. It was examined from DSC thermogram and anisotropy test that the degree of crystallinity of the lipid phase decreased and the lipid matrix became less ordered when octyldodecanol, a long chain fatty alcohol, was added into the solid lipid. The oxidative stability of α -tocopherol in NLC was remarkably improved compared to that in solution or emulsion under high temperature (45 °C) and UV radiation, which was verified through DPPH test and peroxide value measurement.

The controlled aggregation and tunable viscosity of nanostructured lipid carrier dispersions

Abstract Applications of solid lipid nanoparticles (SLNs) in drug delivery and the encapsulation of bioactive, lipophilic compounds have been hindered by the tendency of SLN suspensions to undergo uncontrolled aggregation due to polymorphic transformation of the lipid crystals. Second generation lipid nanoparticle systems have been developed by mixing liquid lipid with solid lipid to form more stable nanostructured lipid carriers (NLCs). In this study, we investigated the effect of chemical formulation on the aggregation behavior and rheology of NLC dispersions. We found that NLC suspension viscosity could be modified by an order of magnitude by controlling particle aggregation with different surfactant and/or oil concentrations. The viscosity could be tuned by decreasing the amount of surfactant and/or oil to achieve a desired level of particle aggregation. Oscillatory sweep tests showed that non-aggregated and aggregated dispersions exhibited typical behaviors of a viscoelastic liquid and a viscoelastic solid, respectively. Modeling results suggested a stronger particle–particle bonding force and a higher aggregation efficiency as the amount of surfactant and/or oil was decreased. Both experimental and modeling results indicated that aggregated samples had an interconnected network structure, while no indication of network formation was observed for non-aggregated samples. Collectively these results suggest that controlled NLC aggregation can be exploited to develop dispersions with tunable viscosity for applications such as rheology modification.

Curcumin-loaded nanostructured lipid carriers (NLCs) for nasal administration: design, characterization, and in vivo study

Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as a carrier for curcumin (CRM). The CRM-loaded NLC developed as a particle with the size of 146.8 nm, a polydispersity index of 0.18, an entrapment efficiency (EE) of 90.86%, and the zeta potential (ZP) of −21.4 mV. Besides, the increased cytotoxicity of CRM-NLC than that of CRM to astrocytoma-glioblastoma cell line (U373MG) in the cancer cell lines was observed. Results of biodistribution studies showed higher drug concentration in brain after intranasal administration of NLCs than PDS. The results of the study also suggest that CRM-NLC is a promising drug delivery system for brain cancer therapy.

Preparation and characterization of a nanostructured lipid carrier for a poorly soluble drug

The aim of this study was to prepare a stable nanostructured lipid carrier (NLC) with biocompatible lipids and surfactants (Pluronic F68 and Cremophor EL) by high-pressure homogenization (HPH). Surface tension measurements were used to choose the suitable ratio between Pluronic F68 and Cremophor EL. Hydrophobic anticancer drug docetaxel (DTX) was used as an active pharmaceutical ingredient (API). The mean particle size of docetaxel loaded nanostructured lipid carrier (DTX-NLC), as determined by dynamic light scattering (DLS), was between 120nm and 250nm during the storage period of 30 days, with the entrapment efficiency decreasing from (60.5±5.0)% to (55.3±4.5)%, while zeta potential was slightly changed from (−43.19±3.6)mV to (−40.12±4.3)mV. Transmission electron microscopy (TEM) showed that some of DTX-NLCs have elongated shape. Small angle neutron scattering (SANS) demonstrated that DTX-NLC in solution contained dense core with perfectly smooth surface, while blank NLC had dense core but rough surface. The blank NLC and DTX-NLC showed cubic crystalline structure according to small angle X-ray scattering (SAXS). Wide angle X-ray diffraction (XRD) showed that adding of DTX increased the crystallinity of the NLC. Cytotoxicity was studied by MTT assay against Hela cells. The data suggested that blank NLC was biocompatible with HeLa cells while the DTX-NLC was more cytotoxic than pure DTX at the same drug concentration. DTX-NLC could be taken up into the cells more than pure DTX, which could be attributed to the better solubility of DTX after loading into NLC.

The effect of oil type on the aggregation stability of nanostructured lipid carriers

Second generation lipid systems for the delivery of bioactive compounds have been developed by mixing a liquid carrier oil with a solid lipid to form so-called nanostructured lipid carriers (NLCs). In this study, we investigated the effect of different liquid carrier oils on the crystallization and aggregation behavior of tristearin NLC dispersions. We found that NLC suspension stability was strongly affected by the type and amount of the carrier oil. As the oil concentration was increased, the crystallization and melting temperatures decreased, the polymorphic transformation rate increased, the particles became more spherical, and suspension stability was enhanced. These results suggest that oil trapped within the growing crystal matrix accelerated polymorphic transformation but retarded the large shape change normally associated with the transformation. We also found that considerably less surfactant was necessary to produce stable NLC suspensions than was required to stabilize solid lipid nanoparticle (SLN) suspensions without a carrier oil. Based on preliminary simulation results, we hypothesized that improved NLC suspension stability was attributable to both reduced particle shape change, which created less new surface area to be covered by surfactant, and increased mobility of surfactant molecules, which resulted in available surfactant being more efficient at covering created surface area.

Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: Characterization, stability assessment and cytotoxicity

Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines.

Development of thermodynamically stable nanostructured lipid carrier system using central composite design for zero order permeation of Econazole nitrate through epidermis

The investigation was aimed at developing thermodynamically stable topical delivery system of nanostructured lipid carrier of econazole nitrate (EN) for the treatment of deep seated fungal infection by improving its permeability. Fifteen formulations (F1–F15) of nanostructured lipid carriers (NLCs) were prepared by solvent injection technique using central composite design and characterized for particle size and % entrapment efficiency. Closeness in the results, guided the selection of five NLC formulations which were formulated as hydrogels (G1–G5) using Carbopol 934. The permeation studies of gels demonstrated G3 with flux rate of 3.21 ± 0.03 µg/cm2/min (> target flux of 1.46 µg/cm2/min) as the best formulation that exhibited zero order permeation. The amount of drug/unit area demonstrated linear dependency on flux rate. Confocal laser scanning microscopy demonstrated penetration of rhodamine red till the stratum basale due to hydration of stratum corneum. Hydrogel G3 containing NLC formulation (F5) was selected as the optimized topical gel. TEM of F5 revealed spherical particles that presented low recrystallization index of 72.35%. Stability profile for 90 days revealed insignificant change (p < 0.05) in the particle size and zeta potential indicating substantial stability of the system. Thus, EN-loaded NLC indicated better permeability and thermodynamic stability as effective topical delivery system for deep seated fungal infection.

Optimization of nanostructured lipid carriers for lutein delivery

Nanostructured lipid carrier (NLC) systems were developed using response surface methodology to optimize the concentrations of lipophilic and hydrophilic surfactants based on the size of the resulting NLC. From preliminary experiments, a formulation composed of Precirol, Myverol, and Pluronic formed a stable NLC dispersion. Concentrations of the surfactants, Myverol and Pluronic, were optimized by a central composite design and response surface methodology. Lutein (phylloquinone) was used as a lipophilic drug in the NLC system. The particle size and polydispersion index of the NLC were measured using photon correlation spectroscopy. The ultrasonication duration and drug load were found to significantly impact the particle size of the NLCs prepared. The prepared NLCs were examined by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and transmission electron microscopy (TEM) and found to have an imperfect crystalline lattice and a spherical morphology. The lutein-loaded NLCs had high release rates of the drug in simulated intestinal fluid compared to simulated gastric fluid using modified Franz diffusion cells. Sustained-release lutein delivery was achieved using NLC technology.

Effect of surfactants on the formation and characterization of a new type of colloidal drug delivery system: Nanostructured lipid carriers

Nanostructured lipid carriers (NLC) consisted of solid lipid and liquid lipid are a new type of colloidal drug delivery system, which offer the advantage of improved drug loading capacity and release properties. Surfactants play important roles in the formation and characterization of NLC. In order to investigate the influence of surfactants on properties of NLC, four types of surfactants and their mixtures were used in the absence of model drugs thereby avoiding the interaction between surfactants and drugs. The hot high-pressure homogenization method was employed to produce NLC and the physicochemical properties of NLC, such as particle size distribution, zeta potential and DSC analysis were investigated. The results indicated that ionic surfactants such as sodium deoxycholate (SDC), showed obviously low emulsification efficiency in the preparation. However, it increased the zeta potential of nanoparticles leading to improve the physical stability of the system. Non-ionic emulsifier, especially Poloxamer 188, offered additional steric stabilization effect avoiding aggregation of the nanoparticles in the colloidal system. The formulation in the study combined four types of additives including ionic surfactant (SDC), non-ionic emulsifier (Poloxamer 188 and Tween-80), and Lecithin to obtain favorably stable NLC drug delivery system, which could stabilize for more than 1 year without phase separation at 4 °C.