Size Of Solid Lipid Nanoparticles Research Articles

Cyclosporine A-Loaded Solid Lipid Nanoparticles: Ocular Tolerance and In Vivo Drug Release in Rabbit Eyes

Purpose: To determine the in vivo efficacy of cyclosporine A-loaded solid lipid nanoparticles (SLNs) in rabbit eyes.Methods: SLNs were prepared and administered to the cul-de-sac of rabbits, and the drug amount in aqueous humor was detected by high performance liquid chromatography (HPLC). The irritation was evaluated by modified Draize testing.Results: The particle size of SLNs was detected as 225.9 ± 5.5 nm with a negative surface charge. Aqueous humor drug levels reached 50.53 ng/mL, and there was no serious irritation in rabbit eyes.Conclusions: Topical ophthalmic efficacy of cyclosporine A was enhanced via administration of SLNs.

The effect of cetyl palmitate crystallinity on physical properties of gamma-oryzanolencapsulated in solid lipid nanoparticles

This present study was aimed at investigating the effect of the crystallinity of cetylpalmitate based solid lipid nanoparticles (SLNs) on the physical properties ofγ-oryzanol-loaded SLNs. SLNs consisting of varying ratios of cetyl palmitate andγ-oryzanol were prepared. Their hydrodynamic diameters were inthe range 210–280 nm and the zeta potentials were in the range−27 to−35 mV. The size of SLNs increased as the amount of cetyl palmitate decreased whereas no significantchange of zeta potentials was found. Atomic force microscopy pictures indicated the presenceof disc-like particles. The crystallinity of SLNs, determined by differential scanning calorimetryand powder x-ray diffraction, was directly dependent on the ratio of cetyl palmitate toγ-oryzanol and decreased with decreasing cetyl palmitate content in the lipidmatrix. Varying this ratio in the lipid mix resulted in a shift in the meltingtemperature and enthalpy, although the SLN structure remained unchanged as anorthorhombic lamellar lattice. This has been attributed to a potential inhibition byγ-oryzanol during lipid crystal growth as well as a less ordered structure of the SLNs. Theresults revealed that the crystallinity of the SLNs was mainly dependent on the solid lipid,and that the crystallinity has an important impact on the physical characteristics ofactive-loaded SLNs.

Cyclosporine A Loaded Solid Lipid Nanoparticles: Optimization of Formulation, Process Variable and Characterization

Solid lipid nanoparticles (SLNs) loaded with Cyclosporine A using glyceryl monostearate (GMS) and glyceryl palmitostearate (GPS) as lipid matrices were prepared by melt-homogenization using high-pressure homogenizer. Various process parameters such as homogenization pressure, homogenization cycles and formulation parameters such as ratio of drug: lipid, emulsifier: lipid and emulsifier: co-emulsifier were optimized using particle size and entrapment efficiencies as the dependent variables. The mean particle size of optimized batches of the GMS SLN and GPS SLN were found to be 131 nm and 158 nm and their entrapment efficiencies were 83 +/- 3.08% and 97 +/- 2.59% respectively. To improve the handling processing and stability of the prepared SLNs, the SLN dispersions were spray dried and its effect on size and reconstitution parameters were evaluated. The spray drying of SLNs did not significantly alter the size of SLNs and they exhibited good redispersibility. Solid state studies such as Infra Red Spectroscopy and Differential Scanning Calorimetry indicated absence of any chemical interaction between Cyclosporine A and the lipids. Scanning Electron Microscopy of optimized formulations showed spherical shape with smooth and non porous surface. In vitro release studies revealed that GMS based SLNs released the drug faster (41.12% in 20 hours) than GPS SLNs (7.958% in 20 hours). Release of Cyclosporine A from GMS SLN followed Higuchi equation better than first order while release from GPS SLN followed first order better than Higuchi model.

Effect of Solid Lipid Nanoparticles Formulation Compositions on Their Size, Zeta Potential and Potential for In Vitro pHIS-HIV-Hugag Transfection

This work was conducted to determine model equations describing the effect of solid lipid nanoparticles (SLN) formulation compositions on their size and zeta potential using the face-centered central composite design and to determine the effect of SLN formulation compositions on the potential for in vitro pHIS-HIV-hugag transfection. SLN were prepared by the hot high pressure homogenization technique using cetylpalmitate as lipid matrix at varying concentrations of Tween 80 and Span 85 mixture, dimethyldioctadecyl ammonium bromide (DDAB) and cholesterol. Size and zeta potential used as responses of the design were measured at pH 7.0. The model equations were accepted as statistical significance at p value of less than 0.05. Ability of SLN to form complex with pHIS-HIV-hugag was evaluated by electrophoretic mobility shift assay. In vitro cytotoxicity of SLN was studied in HeLa cells using alamar blue bioassay. The potential of SLN for in vitro pHIS-HIV-hugag transfection was also determined in HeLa cells by western blot technique. SLN possessed diameter in a range of 136-191 nm and zeta potential 11-61 mV depending on the concentrations of surfactant mixture, DDAB and cholesterol. The regression analysis showed that the model equations of responses fitted well with quadratic equations. The ability of SLN to form complex with pHIS-HIV-hugag was also affected by formulation compositions. In vitro cytotoxicity results demonstrated that HeLa cells were not well tolerant of high concentrations of SLN but still survived in a range of 100-200 microg/ml of SLN in culture medium. The results of transfection study showed ability of SLN to use as a vector for in vitro pHIS-HIV-hugag transfection. However, their potential for in vitro transfection was lower than the established transfection reagent. Size and zeta potential of SLN could be predicted from their quadratic model equations achieved by combination of three variables surfactant, DDAB and cholesterol concentrations. In addition, these variables also affected the potential of SLN as a vector for in vitro pHIS-HIV-hugag transfection. The results here provide the framework for further study involving the SLN formulation design for DNA delivery.

Influence of the Formulation for Solid Lipid Nanoparticles Prepared with a Membrane Contactor

Solid lipid nanoparticles (SLN) were introduced in the 1990s as an alternative to microemulsions, polymeric nanoparticles, and liposomes. The SLN are reported to have several advantages, i.e., their biocompatibility and their controlled and targeted drug release. In this paper, we present a new process for the preparation of SLN using a membrane contactor to allow large scale production. The lipid phase is pressed, at a temperature above the melting point of the lipid, through the membrane pores allowing the formation of small droplets. The lipid droplets are then detached from the membrane pores by the aqueous phase flowing tangentially to the membrane surface. The SLN are formed by the following cooling of the preparation below the lipid melting point. The influence of the aqueous phase and lipid phase formulations on the lipid phase flux and on the SLN size are studied. It is shown that SLN are obtained with a lipid phase flux between 0.21 and 0.27 m3/h.m2, SLN size between 175 and 260 nm. The advantages of this new process are demonstrated to be its facility of use and its scaling-up ability.

Pharmacokinetics, tissue distribution and bioavailability of nitrendipine solid lipid nanoparticles after intravenous and intraduodenal administration

Purpose: The aim of this research was to study whether the bioavailability of nitrendipine (NDP) could be improved by administering nitrendipine solid lipid nanoparticles (SLN) duodenally to rats.Methods: Nitrendipine was incorporated into SLN prepared by hot homogenization followed by ultrasonication method. SLN were produced using various triglycerides (trimyristin, tripalmitin and tristearin), soy phosphatidylcholine 95%, poloxamer 188 and charge modifiers (dicetyl phosphate, DCP and stearylamine, SA). Particle size and charge measurements were made with a Malvern Zetasizer. Pharmacokinetics of nitrendipine SLNs (NDP-SLNs) after intravenous (i.v.) and intraduodenal (i.d.) administration to conscious male Wistar rats were studied. Tissue distribution studies of NDP-SLNs were carried out in Swiss albino mice after i.v. administration and compared to nitrendipine suspension (NDP-Susp).Results: Average size and zeta potential of SLNs of different lipids, with and without charge modifiers ranged from 101.9 ± 3.0 to 123.5 ± 3.0 nm and − 35.1 ± 0.5 to +34.6 ± 2.3 mV, respectively. AUC(0–∞) was increased (up to 4.51-folds) and clearance was decreased (up to 4.54-folds) after i.v. administration of NDP-SLNs with and without charge modifiers compared to NDP-Susp. Effective bioavailability of NDP-SLNs were 2.81–5.35-folds greater after i.d. administration in comparison with that of NDP-Susp. In tested organs, the AUC and MRT of NDP-SLNs were higher than those of NDP-Susp especially in brain, heart and reticuloendothelial cells containing organs.Conclusions: SLN are suitable drug delivery systems for the improvement of bioavailability of nitrendipine. Negatively and positively charged SLN were better taken up by the liver and brain, respectively.

Preparation of solid lipid nanoparticles using a membrane contactor

Solid lipid nanoparticles (SLN) were introduced at the beginning of the 1990s, as an alternative to solid nanoparticles, emulsions and liposomes in cosmetic and pharmaceutical preparations. The present study investigates a new process for the preparation of SLN using a membrane contactor. The lipid phase is pressed, at a temperature above the melting point of the lipid, through the membrane pores allowing the formation of small droplets. The aqueous phase circulates inside the membrane module, and sweeps away the droplets forming at the pore outlets. SLN are formed by the following cooling of the preparation to room temperature. The influence of process parameters (aqueous phase and lipid phase temperatures, aqueous phase cross-flow velocity and lipid phase pressure, membrane pore size) on the SLN size and on the lipid phase flux is investigated. It is shown that the membrane contactor allows the preparation of SLN with a lipid phase flux between 0.15 and 0.35 m 3/h m 2, and a mean SLN size between 70 and 215 nm. The advantages of this new process are its facility of use, the control of the SLN size by an appropriate choice of process parameters, and its scaling-up abilities.

Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration

Clozapine, a lipophilic effective atypical antipsychotic drug, has very poor oral bioavailability (< 27%) due to first pass effect. Clozapine solid lipid nanoparticles have been developed using various triglycerides (trimyristin, tripalmitin and tristearin), soylecithin 95%, poloxamer 188 and stearylamine as a positive charge inducer by hot homogenization followed by ultrasonication method. Particle size and charge measurements were made with Malvern Zetasizer. Pharmacokinetics of clozapine incorporated in solid lipid nanoparticles (SLNs), after intravenous (i.v.) administration to conscious male Wistar rats were studied. The aim of this research was to find out whether the bioavailability of clozapine can be improved by administering clozapine SLN duodenally to rats. Tissue distribution studies of clozapine SLN and suspension were carried out in Swiss albino mice. Average size and zeta potential of SLNs of different lipids with stearylamine ranged from 96.7 ± 3.8 to 163.3 ± 0.7 nm and 21.3 ± 1.3 to 33.2 ± 0.6 mV, respectively. AUC (0–∞) was increased (up to 2.91-fold) and clearance was decreased (up to 2.93-fold) when clozapine entrapped in SLNs with stearylamine were administered intravenously. Bioavailability of clozapine SLNs were 2.45- to 4.51-fold after intraduodenal administration compared with that of clozapine suspension. In tested organs, the AUC and MRT of clozapine SLNs were higher than those of clozapine suspension especially in brain and reticuloendothelial cell-containing organs. These results indicate that SLN are suitable drug delivery system for the improvement of bioavailability of lipophilic drugs such as clozapine.

5-Fluorouracil과 그 유도체를 함유하는 Solid Lipid Nanoparticles 제조와 평가

Solid lipid nanoparticles(SLNs) are particulate systems for parenteral drug administration and have good biocompatibility and stability. SLNs were prepared with lauric acid, as the lipid core. Tween 20 and tween 80 were used as surfactant. 5-fluorouracil and l-benzoyl-5-fluorouracil were used as model drugs. Drug-loaded SLNs were prepared by the hot homogenization technique in order to evaluate the physical stability, entrapment efficiency of drugs as well as release profile. The particle size of SLNs was nm. By increasing speed, the mean particle size of SLNs was decreased. And entrapment efficiency in the case of using 1-Benzoyl-5-fluorouracil was higher than using 5-Fluorouracil. The higher surfactant concentration, the faster release rate at the range of .

Cosmetic applications for solid lipid nanoparticles (SLN)

Solid lipid nanoparticles (SLN) are novel delivery systems for pharmaceutical and cosmetic active ingredients. This paper highlights advantages of SLN for cosmetic applications. The dependence of the occlusive effect on the particle size of SLN due to film formation is presented by in vitro data. An in vivo study showed that addition of 4% SLN to a conventional o/w cream lead to an increase of skin hydration of 31% after 4 weeks. The application of SLN as physical sunscreens and as active carriers for molecular sunscreens has also been investigated. The amount of molecular sunscreen could be decreased by 50% while maintaining the protection level compared to a conventional emulsion.

Formulation parameters determining the physicochemical characteristics of solid lipid nanoparticles loaded with all-trans retinoic acid.

Solid lipid nanoparticles (SLNs) have gained attention as a colloidal drug carrier, particularly for drugs with limited solubility. The poor aqueous solubility of all-trans retinoic acid (ATRA) has been a limiting factor in its clinical use. This study was undertaken to overcome the solubility limitation of ATRA by loading in SLNs. The physicochemical characteristics of ATRA-loaded SLNs were investigated by particle size analysis, zeta potential measurement, thermal analysis and HPLC determination of ATRA content. The mean particle size of ATRA-loaded SLNs could be reduced (1) by mixing EggPC and Tween 80 as a surfactant and (2) by increasing the total surfactant amount. The smallest mean particle size of SLNs was obtained with 50 mg/g surfactant mixture composed of 54:46% (w/w) EggPC:Tween 80 (154.9 nm). The zeta potential of SLNs could be increased by mixing EggPC, Tween 80 and DSPE-PEG in the surfactant mixture. The zeta potential of SLNs prepared with 50 mg/g surfactant mixture composed of 48:6:46% (w/w) of EggPC:DSPE-PEG:Tween 80 was -38.18 mV. ATRA could be loaded at 2.4% (percentage of lipid matrix) on these SLNs without impairing their physical stability. After freeze-drying, the mean particle size and polydispersity index of ATRA-loaded SLNs were only slightly increased (181.8 vs. 265.2 nm, 0.173 vs. 0.200). Furthermore, no significant change was observed in the SLN-loaded concentration of ATRA and the zeta potential of SLNs after freeze-drying. Taken together, SLN formulation of ATRA with similar characteristics to those of parenteral emulsions could be obtained even after freeze-drying.

Effect of lipid matrix and size of solid lipid nanoparticles (SLN) on the viability and cytokine production of macrophages

Solid lipid nanoparticles (SLN) interact with mononuclear cells following intravenous injection. Little is known about the interaction of SLN with these cells, including cytotoxic effects and a possible up-regulation of pro-inflammatory cytokines. Therefore, we investigated the influence of lipid matrix, concentration, and size of SLN on murine peritoneal macrophages (mφ). mφ were incubated with SLN consisting of different lipid matrices and coated with the same surfactant. Cytotoxicity as assessed by MTT test was found to be concentration-dependent and was dramatically influenced by the lipid matrix. Marked cytotoxic effects were observed when cells were incubated with SLN consisting of stearic acid (STE) or dimethyl-dioctadecylammonium bromide (DDA) at concentrations of 0.01%, whereas SLN consisting of triglycerides, cetylpalmitate or paraffin did not exert major cytotoxic effects at the same concentrations. Cytotoxic effects were most likely caused by products of enzymatic degradation including free stearic acid. Analysis of cytokine production by mφ following incubation with SLN revealed concentration-dependent decreases in IL-6 production. These decreases seemed to be associated with cytotoxic effects. IL-12 and TNF-α production was neither detected in supernatants of mφ treated with SLN at any concentration nor in those of untreated cells. The size of SLN did neither affect cytotoxicity of SLN nor resulted in induction or digression of cytokine production by mφ. In conclusion, results of the present study revealed that the nature of the lipid matrix and the concentration of SLN dramatically impact cytotoxicity of SLN on mononuclear cells. Lipid matrices of SLN should therefore be carefully chosen and tested for later intravenous use.

Surfactant, but not the size of solid lipid nanoparticles (SLN) influences viability and cytokine production of macrophages

After intravenous (i.v.) injection, solid lipid nanoparticles (SLN) interact with mononuclear cells. Murine peritoneal macrophages were incubated with SLN formulations consisting of Dynasan 114 coated with different surfactants. The present study was performed to examine the impact of surfactants, which are important surface defining components of SLN, on viability and cytokine production by macrophages. Cytotoxicity, as assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test, was strongly influenced by the surfactant used being marked with cetylpyridinium chloride- (CPC-) coated SLN at a concentration of 0.001% and further increased at SLN concentrations of 0.01 and 0.1%. All other SLN formulations — containing Poloxamine 908 (P908), Poloxamer 407 (P407), Poloxamer 188 (P188), Solutol HS15 (HS15), Tween 80 (T80), Lipoid S75 (S75), sodium cholate (SC), or sodium dodecylsulfate (SDS) — when used at the same concentrations reduced cell viability only slightly. None of the SLN formulations tested induced cytokine production but a concentration-dependent decrease of IL-6 production was observed, which appeared to be associated with cytotoxic effects. IL-12 and TNF-α were detected neither in supernatants of macrophages treated with SLN at any concentration nor in those of untreated cells. In contrast to the type of surfactant, the size of SLN was found neither to affect cytotoxicity of SLN nor to result in induction or digression of cytokine production by macrophages. In conclusion, testing the effects of surfactants on SLN on activity of macrophages is a prerequisite prior to in vivo use of SLN.

Solid lipid nanoparticles (SLN) for controlled drug delivery II. drug incorporation and physicochemical characterization

Solid lipid nanoparticles (SLN) are a colloidal carrier system for controlled drug delivery. The lipophilic model drugs tetracaine and etomidate were incorporated to study the maximum drug loading, entrapment efficacy, effect of drug incorporation on SLN size, zeta potential (charge) and long-term physical stability. Drug loads of up to 10% could be achieved whilst simultaneously maintaining a physically stable nanoparticle dispersion. Incorporation of drugs showed no or little effect on particle size and zeta potential compared to drug-free SLN. The optimized production parameters previously established for drug-free SLN dispersions can therefore be transferred to drug-loaded systems to facilitate product development.

Solid lipid nanoparticles in lymph and plasma after duodenal administration to rats.

To evaluate the uptake and transport of solid lipid nanoparticles (SLN), which have been proposed as alternative drug carriers, into the lymph and blood after duodenal administration in rats. Single doses of two different concentrations of aqueous dispersions of unlabelled and labelled SLN (average diameter 80 nm) were administered intraduodenally to rats. At different times, samples of lymph were withdrawn by cannulating the thoracic duct and blood was sampled from the jugular vein. Monitoring continued for 45 and 180 minutes, for unlabelled and labelled SLN respectively. The biological samples were analysed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM) and gamma-counting. TEM analysis evidenced SLN in lymph and blood after duodenal administration to rats: the size of SLN in lymph did not change markedly compared to that before administration. The labelled SLN confirmed the presence of SLN in lymph and blood. The uptake and transport of SLN in the lymph, and to a lesser extent in the blood, were evidenced. The in vivo physical stability of SLN may have important implications in designing drug-carrying SLN.