Showing papers on "Solid lipid nanoparticle published in 2006"

A new polymer-lipid hybrid nanoparticle system increases cytotoxicity of doxorubicin against multidrug-resistant human breast cancer cells.

Abstract: This work is intended to develop and evaluate a new polymer–lipid hybrid nanoparticle system that can efficiently load and release water-soluble anticancer drug doxorubicin hydrochloride (Dox) and enhance Dox toxicity against multidrug-resistant (MDR) cancer cells. Cationic Dox was complexed with a new soybean-oil-based anionic polymer and dispersed together with a lipid in water to form Dox-loaded solid lipid nanoparticles (Dox–SLNs). Drug loading and release properties were measured spectrophotometrically. The in vitro cytotoxicity of Dox–SLN and the excipients in an MDR human breast cancer cell line (MDA435/LCC6/MDR1) and its wild-type line were evaluated by trypan blue exclusion and clonogenic assays. Cellular uptake and retention of Dox were determined with a microplate fluorometer. Dox–SLNs were prepared with a drug encapsulation efficiency of 60–80% and a particle size range of 80–350 nm. About 50% of the loaded drug was released in the first few hours and an additional 10–20% in 2 weeks. Treatment of the MDR cells with Dox–SLN resulted in over 8-fold increase in cell kill when compared to Dox solution treatment at equivalent doses. The blank SLN and the excipients exhibited little cytotoxicity. The biological activity of the released Dox remained unchanged from fresh, free Dox. Cellular Dox uptake and retention by the MDR cells were both significantly enhanced (p < 0.05) when Dox was delivered in Dox–SLN form. The new polymer–lipid hybrid nanoparticle system is effective for delivery of Dox and enhances its efficacy against MDR breast cancer cells.

Artemisia arborescens L essential oil-loaded solid lipid nanoparticles for potential agricultural application: Preparation and characterization.

Abstract: The aim of this study was to formulate a new delivery system for ecological pesticides by the incorporation of Artemisia arborescens L essential oil into solid lipid nanoparticles (SLN). Two different SLN formulations were prepared following the high-pressure homogenization technique using Compritol 888 ATO as lipid and Poloxamer 188 or Miranol Ultra C32 as surfactants. The SLN formulation particle size was determined using Photon correlation spectroscopy (PCS) and laser diffraction analysis (LD). The change of particle charge was studied by zeta potential (ZP) measurements, while the melting and recrystallization behavior was studied using differential scanning calorimetry (DSC). In vitro release studies of the essential oil were performed at 35°C. Data showed a high physical stability for both formulations at various storage temperatures during 2 months of investigation. In particular, average diameter of Artemisia arborescens L essential oil-loaded SLN did not vary during storage and increased slightly after spraying the SLN dispersions. In vitro release experiments showed that SLN were able to reduce the rapid evaporation of essential oil if compared with the reference emulsions. Therefore, obtained results showed that the studied SLN formulations are suitable carriers in agriculture.

Preparation, characterization and physico-chemical properties of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC): their benefits as colloidal drug carrier systems.

Abstract: Solid lipid nanoparticles (SLN) have attracted increasing attention by various research groups and companies since the early 1990s. Their advantages over existing traditional carriers have been clearly documented. In addition, modified SLN have been described which are nanostructured lipid carriers (NLC) composed of liquid lipid blended with a solid lipid to form a nanostructured solid particle matrix. NLC combine controlled release characteristics with some advantages over SLN. This paper reviews the production techniques, characterization and physical stability of these systems including destabilizing factors and principles of drug loading, then considers aspects and benefits of SLN and NLC as colloidal drug carriers.

Development and evaluation of topical formulation containing solid lipid nanoparticles of vitamin A.

Abstract: The purpose of this research was to investigate novel particulate carrier system such as solid lipid nanoparticles (SLN) for topical application of vitamin A palmitate and to study its beneficial effects on skin. Topical gels enriched with SLN of vitamin A were prepared. The solid lipid nanoparticulate dispersion was prepared using high-pressure homogenization technique and was incorporated into polymeric gels of Carbopol, Pemulen, Lutrol, and Xanthan gum for convenient application. The nanoparticulate dispersion and its gels were evaluated for various parameters such as particle size, in vitro drug release, in vitro penetration, in vivo skin hydration, and skin irritation. The solid lipid nanoparticulate dispersion showed mean particle size of 350 nm. Differential scanning calorimetry studies revealed no drugexcipient incompatibility. In vitro release profile of vitamin A palmitate from nanoparticulate dispersion and its gel showed prolonged drug release up to 24 hours, which could be owing to embedment of drug in the solid lipid core. In vitro penetration studies showed almost 2 times higher drug concentration in the skin with lipid nanoparticle-enriched gel as compared with conventional gel, thus indicating better localization of the drug in the skin. In vivo skin hydration studies in albino rats revealed increase in the thickness of the stratum corneum with improved skin hydration. The developed formulation was nonirritant to the skin with no erythema or edema and had primary irritation index of 0.00. Thus it can be concluded that SLN represents a promising particulate carrier having controlled drug release, improved skin hydration, and potential to localize the drug in the skin with no skin irritation.

Polymorphic behaviour of Compritol888 ATO as bulk lipid and as SLN and NLC.

Abstract: CompritolR888 ATO (glycerol behenate) is widely used as a pharmaceutical excipient in the field of solid dosage forms due to its lubricating properties. It is an amphiphilic material with a high melting point (approximately 70 degrees C) and, therefore, it can also be used to prepare aqueous colloidal dispersions. The aim of this paper is to study the suitability of CompritolR888 ATO for the production of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for the entrapment of a lipophilic model drug. This study assesses the crystalline structure of the bulk lipid, as well as the changes that occur in its crystal lattice with the addition of 'impurities', such as oil (alpha-tocopherol) and drug (ketoconazole), using DSC and X-ray diffraction analysis before and after thermal stress. Aqueous SLN and NLC dispersions were produced using an appropriate surfactant/co-surfactant system and their physicochemical stability was assessed by PCS, LD, DSC and by WAXS. It was found that the crystalline lattice of CompritolR888 ATO is composed of very small amounts of the unstable alpha polymorphic form characteristic of triacylglycerols, which disappears after thermal stress of bulk lipid. Mixing oils and drug molecules which are soluble in this lipid decreased its lattice organization and, thus, was revealed to be suitable for production of lipid nanoparticles containing ketoconazole. However, particle growth could not be avoided during shelf life.

Investigation of the factors influencing the incorporation of clotrimazole in SLN and NLC prepared by hot high-pressure homogenization.

Abstract: Clotrimazole, a fungicidal effective for the local treatment of cutaneous and mucosal infections, was incorporated into solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC). The aim was to increase its dermal bioavailability and to control drug release, thereby potentially reducing its side effects. Prior to the release studies, the carrier was optimized and characterized by using different techniques. Laser diffractometry (LD), photon correlation spectroscopy (PCS) and scanning electron microscopy (SEM) indicated that SLN were spherical in shape with a mean size of approximately 400 nm. Some aggregation phenomena occurred during preparation of SEM samples due to the lipid character of the carriers. No physico-chemical instability of the drug-loaded lipid nanoparticles was detected during 2 years of storage at different temperatures. X-ray and DSC results suggested that during storage time the drug remained molecularly dispersed in the lipid matrix. Drug associated to SLN and NLC in its crystal form could be excluded.

Tamoxifen Citrate Loaded Solid Lipid Nanoparticles (SLN™): Preparation, Characterization, In Vitro Drug Release, and Pharmacokinetic Evaluation

Abstract: Solid lipid nanoparticles (SLN) were prepared by emulsification and high pressure homogenization technique and characterized by size analysis and differential scanning calorimetry. The influence of experimental factors such as homogenization pressure, time, and surfactant concentration on the nanoparticle size and distribution were investigated to optimize the formulation. Homogenization at 15,000 psi for 3 cycles was found to be optimum and resulted in smaller sized nanoparticles. In case of tristearin SLN (TSSLN), tripalmitin SLN (TPSLN), and glycerol behenate SLN (GBSLN), the relatively smaller sized nanoparticles were obtained with 3% sodium tauroglycocholate. The SLN were loaded with an anticancer agent, tamoxifen citrate (TC). The TC-loaded TSSLN shown lower entrapment efficiency (78.78%) compared to the TPSLN (86.75%) and GBSLN (98.64%). Short term stability studies indicated a significant increase in size of nanoparticles when stored at 500C, compared to those stored at 30 degrees C and 4 degrees C. The particle destabilization upon storage in case of all the types of nanoparticles studied was in the order of day light > artificial light > dark. An ultraviolet (UV) spectrophotometric method of estimation of tamoxifen in rat plasma was developed and validated. The TC-loaded TSSLN was administered to the rats intravenously and the pharmacokinetic parameters in the plasma were determined. The t(1/2) and mean residence time of TC-loaded TSSLN in plasma was about 3.5-fold (p < 0.001) and 3-fold (p < 0.001) higher, respectively, than the free tamoxifen, indicating the potential of TC-loaded TSSLN as a long circulating system in blood. Thus the above mentioned solid lipid nanoparticles can be a beneficial system to deliver tamoxifen to cancer tissues through enhanced permeability and retention (EPR) effect.

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

Abstract: 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 ...

Screening of Lipid Carriers and Characterization of Drug-Polymer-Lipid Interactions for the Rational Design of Polymer-Lipid Hybrid Nanoparticles (PLN)

Abstract: Purpose. The thermodynamics and solid state properties of components and their interactions in a formulation for polymer-lipid hybrid nanoparticles (PLN) were characterized for screening lead lipid carriers and rational design of PLN. Methods. Verapamil HCl (VRP) was chosen as a model drug and dextran sulfate sodium (DS) as a counter-ionic polymer. Solubility parameters of VRP, VRP-DS complex, and various lipids were calculated and partition of VRP and VRP-DS in lipids was determined. Thermodynamics of VRP binding to DS was determined by isothermal titration calorimetry (ITC). The solid state properties of individual components and their interactions were characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Results. Dodecanoic acid (DA) was identified as the best lipid carrier among all lipids tested based on the solubility parameters and partition coefficients. VRP-DS complexation was a thermodynamically favorable process. Maximum binding capacity of DS and the highest drug loading capacity of DA were obtained at an equal ionic molar ratio of DS to VRP. In the PLN formulation, DA remained its crystal structure but had a slightly lower melting point, while VRP-DS complex was in an amorphous form. Conclusions. Drug loading efficiency and capacity of a lipid matrix depend on the VRP-DS binding and the interactions of the complex with the lipid. A combined analysis of solubility parameters and partition coefficients is useful for screening lipid candidates for PLN preparation.

The use of SLN and NLC as topical particulate carriers for imidazole antifungal agents.

Abstract: Two different imidazole antifungal agents have been used as model drugs to be incorporated into solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), once they are very well established as anti-mycotics for the treatment of topical fungal infections. Because of the high mucoadhesive properties and the strong in situ gelling properties of polyacrylic acid polymers, hydrogels prepared with those macromolecules might be a promising vehicle for imidazole-loaded lipid nanoparticles, such as the above-mentioned SLN and NLC. Thus, in this study Carbopol 934 has been selected for the preparation of semi-solid formulations based on SLN and NLC. Formulations have been stored at three different temperatures before and after particle incorporation into polyacrylate hydrogels. The particle size and the chemical stability of incorporated model drugs have been monitored by HPLC analysis for two years. On the day of production 91.7% and 98.7% of clotrimazole, but only 62.1% and 70.3% of ketoconazole have been recovered from SLN and NLC, respectively. More than 95% of clotrimazole but less than 30% of ketoconazole were detected in the developed formulations after a shelf life of two years. Those values showed to be higher than those obtained with reference emulsions of similar composition and droplet sizes. By rheological measurements a pseudoplastic behaviour with thixotropic properties has been characterized for all semi-solid systems.

Methotrexate loaded solid lipid nanoparticles (SLN) for effective treatment of carcinoma.

Abstract: Solid Lipid Nanoparticles (SLN) containing Methotrexate (MTX), an anticancer drug for intravenous administration was formulated and characterized. The SLN dispersions with MTX, stearic acid, and soya lecithin in the ratio of 1:4:1, 1:4:1.5, and 1:4:2, sodium taurodeoxycholate and distilled water were prepared by micro emulsification solidification method. The results show that the prepared MTX-SLN particles (with MTX-Stearic acid-Soya lecithin--1:4:2) have an average size of 270 nm with 51.3% drug entrapment. The in-vitro release was attained up to 15th h. The pharmacokinetic study reveals that the half-life and MRT of SLNs were higher than MTX solution. The life span of EAC (Ehrlich Ascite Carcinoma) bearing mice was increased when treated with MTX-SLNs (Methotrexate nanoparticles). These results clearly indicate that SLNs are a promising sustained release drug targeting system for lipophilic antitumour drugs.

Pharmaceutical compositions for lipophilic drugs

Abstract: Stable solutions of lipophilic drugs, such as cyclosporin, forming a polar lipid self-emulsifying drug delivery system. The solutions can include lipophilic drugs, such as cyclosporin, dissolved in a polar lipid, such as having a C 6 -C 12 fatty acid monoglyceride content of at least about 50%, surfactants and triglycerides. The composition forms a fine emulsion on exposure to water. The encapsulated dosage form of this composition needs neither a hydrophilic component nor air-tight blister packaging, and is particularly suitable for oral administration.

Influence of the formulation for solid lipid nanoparticles prepared with a membrane contactor.

Abstract: 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 advantag...

Solid lipid nanoparticles (SLN)--effects of lipid composition on in vitro degradation and in vivo toxicity

Abstract: Solid lipid nanoparticles (SLN) composed of two different lipid matrices were produced to assess their in vivo toxicity in mice. Matrix substances were (i) Compritol (glycerol behenate), a physiological lipid with GRAS status (generally recognized as safe [FDA]), and (ii) cetyl palmitate, a less physiological compound. Physicochemical data proved the suitability of SLN batches for intravenous administration. To assess the in vivo toxicity of produced batches, 400 microl SLN dispersion (lipid content 10% [m/m]) were administered to mice via a bolus injection for six times within a period of 20 days (high dose administration). Additionally, a multiple low dose administration was performed with Compritol-SLN as well (200 microl SLN dispersion, lipid content 2.5% [m/m]). Hepatic and splenic tissues were analysed histologically. In vivo results were dependent on the lipid matrix, as well as on the dose administered. For cetyl palmitate containing SLN no pathological results were obtained, while high dosed Compritol containing formulations led to accumulation of the lipid in liver and spleen and subsequently to pathological alterations. These alterations were found to be partially reversible within six weeks after completing intravenous administration. Liver architecture was nearly recovered. In contrast, low dosed Compritol SLN were well tolerated. Lipid accumulation and pathological alterations of high dosed Compritol SLN were attributed to the slow degradation of the Compritol matrix which could be shown by performing in vitro studies in human plasma.

Paclitaxel-Loaded Lipid Nanoparticles Prepared by Solvent Injection or Ultrasound Emulsification

Abstract: Lipid nanoparticles were fabricated as an injectable carrier system for paclitaxel. The components for the lipid matrix were based on phospholipids, and sucrose fatty acid ester was used as an emulsifier. Formulation prepared with solvent injection has a slightly larger particle size (187.6 nm) than the formulation (147.7 nm) prepared with ultrasound emulsification. Differential scanning calorimetry results indicated that paclitaxel entrapped in the lipid nanoparticles existed in an amorphous state in the lipid matrix. In vitro drug release was rather slow; only 12.5-16.5% of the drug released from the formulations within 14 days. Lipid nanoparticles demonstrated their potential as a promising pharmaceutical formulation of paclitaxel.

In situ evading of phagocytic uptake of stealth solid lipid nanoparticles by mouse peritoneal macrophages.

Abstract: Stealth solid lipid nanoparticles (SSLN) were prepared and evaluated for the effect of evading phagocytic uptake by mouse peritoneal macrophages in situ. Fluorescent SSLNs were prepared by emulsion/evaporation with rhodamine B as the fluorescent marker and polyoxyethylene stearate as stealth agent in a stearic acid matrix. Macrophages were induced chemically through intraperitoneally injecting 1% sodium thioglycolate. After 4 days of cultivation, SSLNs suspension was injected intraperitoneally and phagocytosis taken out in situ. At definite time intervals, peritoneal fluid was drawn out and analyzed by flow cytometer. Maximum uptake by macrophages was observed at 2 hr after injection of nanoparticles. At all time intervals, phagocytic uptake of Solid lipid nanoparticles (SLNs) was better than SSLNs. Longer and dense polyethylene glycol chains led to reduced uptake by macrophages. Both SSLNs and SLN had uptake by macrophages to some extent, and the in situ model was suitable for evaluating interactions between cells and nanoparticles.

Solid Lipid Nanoparticles

Abstract: In the last decade of the last century, solid lipid nanoparticles (SLN) have been introduced to the literature as a novel carrier system for cosmetic active ingredients and pharmaceutical drugs. SLN consist of biodegradable physiological lipids or lipidic substances and stabilisers which are generally recognised as safe (GRAS) or have a regulatory accepted status. Compared to other delivery systems such as liposomes, microemulsions and polymeric nanoparticles, SLN possess various advantages. Examples are production without organic solvents, long time physical stability and the possibility of protection of chemically labile actives inside the particles. This chapter describes the composition, production procedures, characterisation of quality and stability of SLN dispersions and describes possibilities for application of this colloidal carrier system.

Preparation of oridonin-loaded solid lipid nanoparticles and studies on them in vitro and in vivo

Abstract: Oridonin, a lipophilic Chinese medicine, has very low oral bioavailability due to its poor solubility. Solid lipid nanoparticle (SLN) delivery systems of oridonin have been formed using stearic acid, soybean lecithin and pluronic F68 in our studies to overcome this problem. Emulsion evaporation–solidification at low temperature was used to prepare SLN dispersions. The particle size and morphology were examined by transmission electron microscopy (TEM), and the zeta potential was measured by a television micro-electrophoresis apparatus. Process and formulation variables have been studied and optimized on the basis of entrapment efficiency. Differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD) studies were performed to characterize the state of the drug. In vitro release studies were performed in phosphate-buffer solution (PBS) (pH 7.4). The tissue distribution in mice and the pharmacokinetics in rabbits were studied to evaluate the tissue targeted property of SLNs. Stable SLN formulations of oridonin having a mean size range of 15–35 nm and mean zeta potential −45.07 mV were developed. More than 40% oridonin was entrapped in SLNs. DSC and PXRD analysis showed that oridonin is dispersed in SLNs in an amorphous state. The release pattern of the drug was analysed and found to follow the Higuchi equations. In vivo studies demonstrated that oridonin-loaded SLNs obviously increased the concentration of oridonin in liver, lung and spleen, while its distribution in heart and kidney decreased.