Showing papers on "Solid lipid nanoparticle published in 2005"

The Impact of Nanobiotechnology on the Development of New Drug Delivery Systems

Abstract: Nanotechnology, or systems/devices manufactured at the molecular level, is a multidisciplinary scientific field undergoing explosive development. A part of this field is the development of nanoscaled drug delivery devices. Nanoparticles have been developed as an important strategy to deliver conventional drugs, recombinant proteins, vaccines and more recently nucleotides. Nanoparticles and other colloidal drug delivery systems modify the kinetics, body distribution and drug release of an associated drug. Other effects are tissue or cell specific targeting of drugs and the reduction of unwanted side effects by a controlled release. Therefore nanoparticles in the pharmaceutical biotechnology sector improve the therapeutic index and provide solutions for future delivery problems for new classes of so called biotech drugs including recombinant proteins and oligonucleotides. This review discusses nanoparticular drug carrier systems with the exception of liposomes used today, and what the potential and limitations of nanoparticles in the field of pharmaceutical biotechnology are.

Polysorbate-stabilized solid lipid nanoparticles as colloidal carriers for intravenous targeting of drugs to the brain: Comparison of plasma protein adsorption patterns

Abstract: Plasma proteins enriched on the surface of drug-delivery-purpose nanoparticles are regarded as key factors for determination of in vivo organ distribution after intravenous injection. Polysorbate 80-coated polybutylcyanoacrylate (PBCA) nanoparticles, preferentially adsorbing apolipoprotein E (apoE) on their surface, have previously been considered to deliver various drugs to the brain. In the present study, in vivo well tolerable solid lipid nanoparticles (SLN) using different types of polysorbates as stabilizers were produced. The influence of the different surfactants on in vitro adsorption of human plasma proteins was investigated using two-dimensional polyacrylamide gel electrophoresis (2-DE). Possible correlations of different amounts of adsorbed apoE to the hydrophilic-lipophilic balance (HLB) of the polysorbates are shown and discussed. Apolipoprotein C-II, albumin and immunoglobulin G, which are also decisive plasma proteins with regard to site-specific drug delivery of intravenously injected carriers to the brain, are compared with regard to adsorption. Moreover, certain similarities to the plasma protein adsorption patterns of previously analysed brain-specific PBCA nanoparticles could be detected. Despite some differences in adsorption behavior of proteins on the surface of polysorbate-stabilized SLN and PBCA nanoparticles, we conclude that in both cases polysorbate 80 might have the highest potential to deliver drugs to the brain.

Solid lipid nanoparticles as drug delivery systems.

Abstract: For a decade, trials have been made to utilize solid lipid nanoparticles (SLNs) as alternative drug delivery systems to colloidal drug delivery systems such as lipid emulsions, liposomes, and polymeric nanoparticles. Various lipid matrices, surfactants, and other excipients used in formulation, preparation methods, sterilization and lyophilization of SLNs are discussed in this article. Entrapment efficiency of drug carrier and its effect on physical parameters, drug release, and release mechanisms of various compositions are reviewed and discussed. Important points in characterization and stability of SLNs are outlined. Various in vitro studies carried out by different research groups are mentioned in addition to in vivo evaluation. Exploitation potential of SLNs to administer by various routes of administration are covered. Passive and active drug targeting using SLNs are presented.

SLN and NLC for topical delivery of ketoconazole.

Abstract: The clinical use of ketoconazole has been related to some adverse effects in healthy adults, specially local reactions, such as severe irritation, pruritus and stinging. The purpose of the present work is the assessment of ketoconazole stability in aqueous SLN and NLC dispersions, as well as the physicochemical stability of these lipid nanoparticles, which might be useful for targeting this drug into topical route, minimizing the adverse side effects and providing a controlled release. Lipid particles were prepared using Compritol®888 ATO as solid lipid. The natural antioxidant α-tocopherol was selected as liquid lipid compound for the preparation of NLC. Ketoconazole loading capacity was identical for both SLN and NLC systems (5% of particle mass). SLN were physically stable as suspensions during 3 months of storage, but the SLN matrix was not able to protect the chemically labile ketoconazole against degradation under light exposure. In contrast, the NLC were able to stabilize the drug, but the aqueous ...

Solid Lipid Nanoparticles (SLN) and Oil-Loaded SLN Studied by Spectrofluorometry and Raman Spectroscopy

Abstract: Recently, colloidal dispersions made of mixtures from solid and liquid lipids have been described to overcome the poor drug loading capacity of solid lipid nanoparticles (SLN). It has been proposed that these nanostructured lipid carriers (NLC) are composed of oily droplets, which are embedded in a solid lipid matrix. High loading capacities and controlled release characteristics have been claimed. It is the objective of the present paper to investigate these new NLC particles in more detail to obtain insights into their structure. Colloidal lipid dispersions were produced by high-pressure homogenization. Particle sizes were estimated by laser diffraction and photon correlation spectroscopy. The hydrophobic fluorescent marker nile red (NR) was used as model drug, and by fluorometric spectroscopy, the molecular environment (polarity) was elucidated because of solvatochromism of NR. The packaging of the lipid nanoparticles was investigated by Raman spectroscopy and by densimetry. The light propagation in lipid nanodispersions was examined by refractometry to obtain further insights into the nanostructural compositions of the carriers. Fluorometric spectroscopy clearly demonstrates that NLC nanoparticles offer two nanocompartments of different polarity to accommodate NR. Nevertheless, in both compartments, NR experiences less protection from the outer water phase than in a nanoemulsion. In conventional SLN, lipid crystallization leads to the expulsion of the lipophilic NR from the solid lipid. Measurements performed by densimetry and Raman spectroscopy confirm the idea of intact glyceryl behenate lattices in spite of oil loading. The lipid crystals are not disturbed in their structure as it could be suggested in case of oil incorporation. Refractometric data reveal the idea of light protection because of incorporation of sensitive drug molecules in NLC. Neither SLN nor NLC lipid nanoparticles did show any advantage with respect to incorporation rate compared to conventional nanoemulsions. The experimental data let us conclude that NLC lipid nanoparticles are not spherical solid lipid particles with embedded liquid droplets, but they are rather solid platelets with oil present between the solid platelet and the surfactant layer.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) -- structural investigations on two different carrier systems.

Abstract: Two different types of colloidal lipid particles are presented and compared as innovative carrier systems. Size distribution and storage stability of formulations produced by hot high pressure homogenisation in lab and medium scale production were investigated by laser diffractometry (LD) and photon correlation spectroscopy (PCS). Nanoparticles were characterised by their melting and recrystallisation behaviour recorded by differential scanning calorimetry (DSC). Electron microscope investigations were also carried out showing the particulate character of these carriers. Reasons for observed differences in loading capacity are discussed and possibilities for dermal application are described.

Skin moisturizing effect and skin penetration of ascorbyl palmitate entrapped in solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) incorporated into hydrogel.

Abstract: This study was performed as a complimentary to our previous study regarding the chemical stability of ascorbyl palmitate (AP) in solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, in nanoemulsion (NE) incorporated into a hydrogel produced by high pressure homogenization. AP is known as an effective antioxidant that protects tissue integrity similar to vitamin C. Recently, its moisturizing activity in conventional topical formulations was found to be high. The aim of the present study was to investigate the moisturizing potential of AP in SLN and NLC incorporated into hydrogel as colloidal carrier systems. It has been known that SLN and NLC have occlusive effects, but AP incorporation moisturized skin significantly better than placebo in short-term (p < 0.001) and long-term trials (p < 0.01) for both SLN and NLC. In the second part of the study, SLN and NLC were found to sustain the penetration of AP through excised human skin about 1/2 and 2/3 times compared to NE (p < 0.001 and p < 0.01), respectively, due to the solid state of Witepsol E85 in the lipid phase.

Nanosuspension Formulations for Low-Soluble Drugs: Pharmacokinetic Evaluation Using Spironolactone as Model Compound

Abstract: Various particle sizes of spironolactone as a model low solubility drug were formulated to yield micro-and nanosuspensions of the type solid lipid nanoparticles and DissoCubes. Seven oral and one i.v. formulations were tested in an in vivo pharmacokinetic study in rats with the aim of characterizing the bioavailability of spironolactone on the basis of its metabolites canrenone and 7-alpha-thiomethylspirolactone. In addition, a dose escalation study was carried out using nonmicronized spironolactone suspension as well as a nanosuspension type DissoCubes. On the basis of AUC as well as Cmax ratios, three groups of formulations were distinguished. The biggest improvement was seen with a solid lipid nanoparticle formulation yielding a 5.7-fold increase in AUC for canrenone and a similar improvement based on the Cmax metric, followed by a group of three formulations containing nanosized, micronized, and coarse drug material and surfactant. The DissoCubes nanosuspension yielded highly significant improvements in bioavailability averaging 3.3-fold in AUC and 3.0-fold in terms of Cmax for canrenone. The third class encompasses all other formulations, which showed very little to no improvement in bioavailability. The results show that the particle size minimization was not the major determining factor in the bioavailability improvement. Rather, the type of surfactant used as stabilizer in the formulations was of greater importance. Improvement in drug solubility in the intestine as well as in dissolution rate of spironolactone are the most likely mechanisms responsible for the observed effect, although additional mechanisms such as permeability enhancement may also be involved.

Solid Lipid Nanoparticles Bearing Flurbiprofen for Transdermal Delivery

Abstract: Topical application of the drugs at the pathological sites offer potential advantages of delivering the drug directly to the site of action and thus producing high tissue concentrations of the drug. The solid lipid nanoparticles (SLN) bearing flurbiprofen were prepared by microemulsion method by dispersing o/w microemulsion in a cold aqueous surfactant medium under mechanical stirring. The SLN gel was prepared by adding SLN dispersion to polyacrylamide gel prepared by using polyacrylamide (0.5%), glycerol (10%), and water (69.5%). Shape and surface morphology was determined by scanning electron microscopy that revealed fairly spherical shape of the formulation. Percent drug entrapment was higher in SLN dispersion in comparison to SLN gel formulations. In vitro drug release, determined using cellophane membrane, showed that SLN dispersion exhibited higher drug release compared with SLN gel formulations. Both the SLN dispersion and SLN-gel formulation possessed a sustained drug release over a 24-hr period, ...

Functionalized solid lipid nanoparticles and methods of making and using same

Abstract: In one aspect, the invention relates to functionalized solid lipid nanoparticles comprising a neutral lipid and a first functionalized polymer comprising at least one ionic or ionizable moiety and methods for providing same. In a further aspect, the invention relates to tumor targeting therapeutic systems, multimodal diagnostic therapeutic systems, thermoresponsive payload delivery systems, magnetic-driven targeting systems, therapeutic diagnostic systems, stabilized ink compositions, and cosmetic formulations comprising the solid lipid nanoparticles of the invention. In a further aspect, the invention relates to methods of delivering at least one biologically active agent, pharmaceutically active agent, magnetically active agent, or imaging agent across the blood-brain barrier, across a cellular lipid bilayer and into a cell, and to a subcellualr structure. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Design and characterization of a new drug nanocarrier made from solid-liquid lipid mixtures.

Abstract: The classical lipid nanoparticles that have been proposed for drug delivery are composed of solid lipids. Due to their composition, these nanoparticles have a limited drug loading and controlled release capacity. The present work was aimed at modifying the inner structure of nanoparticles made of tripalmitin, lecithin, and poly(ethylene glycol) (PEG)-stearate with the incorporation of a liquid lipid (Miglyol 812 oil). The composition and structural organization of the components of the resulting nanoparticles were characterized by 1H NMR spectroscopy. Any possible changes in the crystalline domains of individual components when in the form of the nanoparticles were investigated by differential scanning calorimetry (DSC) and X-ray diffraction spectroscopy. The results of the NMR analysis indicated a significant incorporation of the oil to the solid nanoparticle matrix. Furthermore, the relaxation time constants as well as the peak width of the 1H NMR spectrum of the nanoparticles suggest the presence of the oil in the form of phase-separated liquid nanoreservoirs within the nanoparticles. This conclusion was supported by the observation of restricted diffusion dynamics for the oil molecules. Interestingly, the incorporation of the oil did not interfere with the crystallization of the solid lipids (tripalmitin and PEG-stearate). In conclusion, a new nanostructure consisting of solid lipids and oily nanodomains was developed. This structural modification of the solid lipid nanoparticles may have an effect on their encapsulation capacity and controlled release properties.

Triptolide loaded solid lipid nanoparticle hydrogel for topical application.

Abstract: Triptolide (TP) has been shown to have anti-inflammatory, antifertility, antineoplastic, and immunosuppressive activity. However, its clinical usage is limited to some extent due to its poor water solubility and toxicity. In order to use innovative ways to administer TP and to overcome or alleviate its disadvantages, controlled-release delivery systems such as solid lipid nanoparticle(SLN(s)) have been developed. In the present paper we describe the preparation and some characterization of specialized delivery systems for TP. The transdermal delivery and anti-inflammatory activity were also evaluated. The results indicated that SLN could serve as an efficient promoter of TP penetrating into skin. Furthermore, different formulations were optimized in this study. The best formulation of SLN, consisted of tristearin glyceride, soybean lecithin, and PEG400MS, with a particle size of 123+/-0.9 nm, polydispersity index (PI) of 0.19, and zeta potential of -45 mV. When this SLN dispersion was incorporated into hydrogel, the nanoparticulate structure was maintained, and aggregation and gel phenomena of the particle could be avoided. The cumulative transdermal absorption rate in 12 h was 73.5%, whereas the conventional TP hydrogel was 45.3%. The anti-inflammatory effect is over two-fold higher than that of conventional TP hydrogel. Moreover, this SLN hydrogel consists of pharmaceutically acceptable ingredients, such as soybean lecithin and lipid, and the nanoparticle can improve safety and minimize the toxicity induced by TP.

A novel approach based on lipid nanoparticles (SLN®) for topical delivery of α-lipoic acid

Abstract: This study describes the development, preparation and characterization of solid lipid nanoparticles (SLN®) containing the novel anti-ageing substance α-lipoic acid. Lipoic acid is chemically labile, i.e. the degradation products possess an unpleasant odour. Therefore, the active was encapsulated in SLN. A lipid with low melting point (Softisan®601) was selected for preparation of active-loaded SLN after screening the solubility of α-lipoic acid in physicochemically different lipids. An entrapment efficiency of 90% (UV analysis) was obtained for all developed formulations using Miranol®Ultra C32 as emulsifying agent. Particle size stability was monitored during 3 months storing the samples at 20°C and at 4°C. Results of DSC analysis confirm that these systems are characterized by a solid-like behaviour, although with a very low crystallinity index.

Physicochemical investigations on the structure of drug-free and drug-loaded solid lipid nanoparticles (SLN) by means of DSC and 1H NMR.

Abstract: A solid lipid nanoparticle (SLN) formulation, based on the lipid Imwitor 900, was developed for the incorporation of the poorly water soluble drug RMEZ98. Physicochemical investigations were undertaken to examine the structure and physical stability of the selected lipid as colloidal dispersion in comparison to the bulk material. Using differential scanning calorimetry (DSC) and proton nuclear magnetic resonance (1H NMR) it could be assessed the influence of the incorporated drug on the structure of the lipid matrix. Investigation of mixtures of Imwitor 900 and RMEZ98 showed an increasing effect on the melting/recrystallization behaviour with increasing drug content (5-30%). DSC and 1H NMR results revealed the formation of a crystalline matrix of SLN when prepared by high pressure homogenization excluding, therefore, the phenomenon of supercooled melt. After preparation of RMEZ98-loaded SLN, the drug remained inside the lipid matrix; however, it exhibited only a small effect on the recrystallization behaviour of Imwitor 900 at the lowest payload required for a therapeutic effect (4% m/m with regard to the lipid matrix). Furthermore, the incorporation of RMEZ98 revealed no distinct influence on the particle size distribution. Imwitor 900 proved to be a suitable lipid for the drug RMEZ98, i.e. possessing a sufficient loading capacity and simultaneously physical stability.

Solid Lipid Nanoparticles Containing Tamoxifen Characterization and In Vitro Antitumoral Activity

Abstract: Solid lipid nanoparticles (SLNs) containing tamoxifen, a nonsteroidal antiestrogen used in breast cancer therapy, were prepared by microemulsion and precipitation techniques. Tamoxifen loaded SLNs seem to have dimensional properties useful for parenteral administration, and in vitro plasmatic drug release studies demonstrated that these systems are able to give a prolonged release of the drug in the intact form. Preliminary study of antiproliferative activity in vitro, carried out on MCF-7 cell line (human breast cancer cells), demonstrated that SLNs, containing tamoxifen showed an antitumoral activity comparable to free drug. The results of characterization studies and of in vitro antiproliferative activity strongly support the potential application of tamoxifen-loaded SLNs as a carrier system at prolonged release useful for intravenous administration in breast cancer therapy.

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for application of ascorbyl palmitate.

Abstract: The aim of this study was to improve the chemical stability of ascorbyl palmitate (AP) in a colloidal lipid carrier for its topical use. For this purpose, AP-loaded solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and for comparison, a nanoemulsion (NE) were prepared employing the high pressure homogenization technique and stored at room temperature (RT), 4 degrees C and 40 degrees C. During 3 months, physical stability of these formulations compared to placebo formulations which were prepared by the same production method, was studied including recrystallization behaviour of the lipid with differential scanning calorimetry (DSC), particle size distribution and storage stability with photon correlation spectroscopy (PCS) and laser diffractometry (LD). After evaluating data indicating excellent physical stability, AP-loaded SLN, NLC and NE were incorporated into a hydrogel by the same production method as the next step. Degradation of AP by HPLC and physical stability in the same manner were investigated at the same storage temperatures during 3 months. As a result, AP was found most stable in both the NLC and SLN stored at 4 degrees C (p > 0.05) indicating the importance of storage temperature. Nondegraded AP content in NLC, SLN and NE was found to be 71.1% +/- 1.4, 67.6% +/- 2.9 and 55.2% +/- 0.3 after 3 months, respectively. Highest degradation was observed with NE at all the storage temperatures indicating even importance of the carrier structure.

Preparation and Pharmacokinetic Evaluation of Tashinone IIA Solid Lipid Nanoparticles

Abstract: Tashinone IIA loaded solid lipid nanoparticles (TA-SLN) coated with poloxamer 188 was prepared by emulsification/evaporation. The TA-SLN was characterized by transmission electron microscope and dynamic light scattering (DLS). The results showed that the TA-SLN had an average diameter of 98.7 nm with a zeta potential of - 31.6 mv and the drug loading of 4.6% and entrapment efficiency of 87.7%. In vitro release experiment showed that the release of Tashinone IIA from TA-SLN was in accordance with the Weibull equation. The best model fitting experimental data was a two-compartment open model with first-order. The area under curve of plasma concentration-time (AUC) and mean residence time (MRT) of TA-SLN were much higher than those of Tashinone IIA control solution (TA-SOL). The results of pharmacokinetic studies in rabbits indicated that the formulation of TA-SLN was successful in providing a delivery of slow release of Tashinone IIA.

Characterization and Body Distribution of β-Elemene Solid Lipid Nanoparticles (SLN)

Abstract: Solid lipid nanoparticles (SLN) containing beta-elemene, a volatile oil used for the treatment of cancer, were prepared by the method combining probe sonication and membrane extrusion. Effects of the formulations and procedures on the characteristics of SLN were investigated. Body distribution of beta-elemene SLN in rats after intravenous administration was compared with that of the commercial emulsion. The results showed that dispersing the surfactant in the melted lipid matrix could obtain smaller particles than that dispersing in the water phase. Increasing the ratio of monostearin in the lipid matrix or the concentration of surfactant reduced the mean volume size of the SLN. Optimized formulation was composed of monostearin and precirol ATO 5 at a mass ratio of 3:7, which was quite stable for 8 months at room temperature. In vitro release of beta-elemene from the SLN was slow and stable without obvious burst release and was found to follow the Higuich equation. After intravenous administration, the beta-elemene levels after 5 min injection of SLN formulation were 1.5, 2.9, and 1.4 times higher than those of beta-elemene emulsion in liver, spleen, and kidney, respectively, while the concentrations of beta-elemene were decreased 30% in heart and lung. Therefore, the SLN containing beta-elemene might be an attractive candidate for the treatment of liver cancer.

Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) for Dermal Delivery

Abstract: There are different approaches to modulate the penetration of active ingredients into the skin, i.e., either to increase the penetration or to minimize it. In general, increase in penetration is desired in case of pharmaceutical actives, either focusing the drug in the upper skin layer for local treatment or to achieve permeation of the skin leading to systemic absorption. A classical example for the latter case is nitroglycerine creams, finally leading to the development of transdermal patches. For cosmetic actives, the penetration to only a limited degree is desired to ensure that the active creates only cosmetic effects and do not lead to a pharmaceutical treatment of the skin. In case of sunscreen formulations, the penetration should be minimized to avoid irritations of the skin or other side effects, such as allergic reactions (1,2). Therefore, depending on the purpose of the topical formulation different requirements might be fulfilled by the dermal formulation. A very simple approach to increase penetration is the use of occlusive formulations. Occlusion can be created by placing a plastic foil with low water permeability onto the skin, and—apart from other effects—the drug molecules are expelled in the same way as it is done in modern transdermal patches. Occlusion can also be created using water impermeable hydrocarbon bases, such as petrolatum. However, the aesthetic appearance of these formulations is not appealing. To reduce its fatty character one can produce water-in-oil (w/o) emulsions, realized in highly occlusive cosmetic night creams. Concerning oil-in-water (o/w) emulsions, they possess the desired ‘‘lighter character’’ but are distinctly less occlusive. Another approach to improve penetration of drugs is the use of particulate carriers in the broadest sense, whichmeans covering liposomes and solid particles, such as nanoandmicroparticlesmade frompolymers or naturalmacromolecules. Phospholipid vesicles have already been described in the 20s of the last century (3) and were rediscovered as a dermal carrier system by Bangham (4) about 30 years ago. Despite intensive investigations of the liposomes in the cosmetic and the pharmaceutical area,