Forgot your password?
New user?
New Window Opens on the Secret Life of Microbes: Scientists Develop First Microbial Profiles of Ecosystems
CAS announces the release of SciFinder Scholar for Mac OS X
Press Releases
Press Releases
| Check out our New Publishers' Select for Free Articles |
Advanced Drug Delivery Reviews (v.59, #6)
Lipid nanoparticles: perspectives and challenges by Maria Rosa Gasco (pp. 377-378).
Sustained release; SLN; Drug delivery system
Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering by Heike Bunjes; Tobias Unruh (pp. 379-402).
Differential scanning calorimetry and X-ray diffraction play a prominent role in the characterization of lipid nanoparticle (LNP) dispersions. This review shortly outlines the measurement principles of these two techniques and summarizes their applications in the field of nanodispersions of solid lipids. These methods are particularly useful for the characterization of the matrix state, polymorphism and phase behavior of the nanoparticles which may be affected by, for example, the small particle size and the composition of the dispersions. The basics of small angle X-ray and neutron scattering which are also very promising methods for the characterization of LNPs are explained in some more detail. Examples for their use in the area of solid LNPs regarding the evaluation of particle size effects and the formation of superstructures in the nanoparticle dispersions are given. Some technical questions concerning the use of the different characterization techniques in the field of LNP research are also addressed.
Keywords: Colloidal drug carriers; Glycerides; Cholesterol esters; Fatty acids; Physicochemical characterization
Structure and dynamics of drug-carrier systems as studied by parelectric spectroscopy by T. Blaschke; L. Kankate; K.D. Kramer (pp. 403-410).
In the field of topical application without or with little systemic side-effects to reach anti-inflammatory or anti-androgeneous effects, nanoparticles as carriers for drugs as beta-methason-17-valerate, prednicarbate, prednisolone, RU 58841-myristate or cyproterone acetate have proven to enhance the transdermal delivery. This enhancement is closely connected to the interaction of the drug molecules with the lipid carrier systems, i.e. incorporation into the carriers or attachment to their surfaces. Whereas the techniques to measure the penetration profiles in the cutaneous region of the skin are well established in the case of fluorescence microscopy applied to thin slices of epidermis or being established in the case of multiphoton microscopy to monitor this fluorescence, the methods for the investigation of the type of interaction between drugs and carrier systems are relatively new: in the case of electron spin resonance the sample volumes have to be restricted to capillary sizes to avoid parelectric losses in the microwave cavities, in the case of the novel method of parelectric spectroscopy we are free from such restrictions. The application of the latter method will be presented here in detail concerning the underlying theory, the experimental aspects as well as the algorithms to extract the parameters of interest from the measured samples. As samples we restrict ourselves to solid lipid nanoparticles coated with different surfactants as carriers for drug-, dye- or spin label molecules.
Keywords: Parelectric spectroscopy; Lipid nanoparticles; Drug targeting; Topical application
Stability of lipid excipients in solid lipid nanoparticles by Anna Radomska-Soukharev (pp. 411-418).
The paper is devoted to the investigation of chemical stability of lipids used as excipients in the production of Solid Lipid Nanoparticles (SLN). Different lipids and amounts of surfactants were considered. Most of the formulations were produced using identical binary surfactant mixtures and concentrations to analyze the effect of the chemical nature of the lipids on their stability in SLN. In some formulations, surfactants were exchanged or their concentration was increased to assess the contribution of surfactants on stability of lipids particles. Solid Lipid Nanoparticles were characterized by photon correlation spectroscopy, laser diffractometry, zeta potential determination and differential scanning calorimetry. Potential effects of lipid crystallinity and modifications were assessed. A gas chromatography (GC) analysis in combination with a method for lipid extraction from aqueous SLN dispersions was used to investigate the chemical stability of the lipid excipients forming the particle matrix. All formulations were produced by the hot homogenization technique. The production process of SLN itself did not affect the chemical stability of lipid excipient forming the particle matrix. The formulations where lipids consisted of trigylicerides showed a negligible decomposition of the structure during incubation at 25 °C. Dynasan 118 showed the highest chemical stability (loss<4%) within two years.
Keywords: Solid lipid nanoparticles; SLN; Physico-chemical stability; Lipid excipients; High pressure homogenization; Surfactants
Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug by A. Hanafy; H. Spahn-Langguth; G. Vergnault; P. Grenier; M. Tubic Grozdanis; T. Lenhardt; P. Langguth (pp. 419-426).
An increasing number of newly developed drugs show bioavailability problems due to poor water solubility. Formulating the drugs as nanosuspensions may help to overcome these problems by increasing saturation solubility and dissolution velocity. In the present study the bioavailability of the poorly soluble fenofibrate following oral administration was investigated in rats. Four formulations were tested: a nanosuspension type DissoCube®, one solid lipid nanoparticle (SLN) preparation and two suspensions of micronized fenofibrate as reference formulations, one suspension in sirupus simplex and a second in a solution of hydroxyethy-cellulose in physiological saline. Both colloidal drug delivery systems showed approximately two-fold bioavailability enhancements in terms of rate and extent compared to the reference formulations. No significant differences were found in AUC0–22 h as well as in Cmax and tmax between the two colloidal delivery systems. In conclusion, nanosuspensions may be a suitable delivery system to improve the bioavailability of drugs with low water solubility.
Keywords: Absorption; Bioavailability enhancement; Oral drug delivery; Nanosuspension; Rat; Nanomedicine; Nanotechnology
Lipid nanoparticles for improved topical application of drugs for skin diseases by Monika Schäfer-Korting; Wolfgang Mehnert; Hans-Christian Korting (pp. 427-443).
Due to the lower risk of systemic side effects topical treatment of skin disease appears favourable, yet the stratum corneum counteracts the penetration of xenobiotics into viable skin. Particulate carrier systems may mean an option to improve dermal penetration. Since epidermal lipids are found in high amounts within the penetration barrier, lipid carriers attaching themselves to the skin surface and allowing lipid exchange between the outermost layers of the stratum corneum and the carrier appear promising. Besides liposomes, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) have been studied intensively. Here we describe the potential of these carrier systems and compare the dermal uptake from SLN and NLC to the one of alternative vehicle systems. A special focus is upon the interactions of active ingredients and the lipid matrix as well as the quantification of dermal penetration.
Keywords: Solid lipid nanoparticles; Nanostructured lipid carriers; Skin; Topical use; Active pharmaceutical ingredient (API); API-carrier interactions; Drug-carrier interactions; Topical glucocorticoids; Benefit/risk ratio
Production of solid lipid nanoparticle suspensions using supercritical fluid extraction of emulsions (SFEE) for pulmonary delivery using the AERx system by P. Chattopadhyay; B.Y. Shekunov; D. Yim; D. Cipolla; B. Boyd; S. Farr (pp. 444-453).
The aims of the current work included: development of a new production method for nanoparticles of water-insoluble drugs in combination with lipids, characterization of the nanoparticles and development of lipid nanosuspension formulations, and investigation of the feasibility of delivering the nanosuspensions as aerosols for inhalation using Aradigm's AERx® Single Dose Platform (SDP) with micron-sized nozzles and the all mechanical AERx Essence™ with sub-micron-sized nozzles. The continuous SFEE method was used for particle precipitation of solid lipid nanoparticles (SLN). The method allowed for production of stable particulate aqueous suspensions of a narrow size distribution, with a volume mean diameter below 30 nm (D99% cumulative volume below 100 nm). Thus the particle size obtained was significantly smaller than previously has been achieved by other techniques. The residual solvent content in the final suspension was consistently below 20 ppm. Drug loading values between 10–20% w/w drug were obtained for model compounds ketoprofen and indomethacin in formulation with lipids such as tripalmitin, tristearin and Gelucire 50/13. It was observed that the loading capacity achieved was higher than the thermodynamic limit of the solubility of the drugs in molten lipids. Lipid nanosuspension formulations were successfully aerosolized using both of the AERx systems. As measured by both cascade impactor and laser diffraction, the aerosol fine particle fraction (FPF) was comparable to drug solution formulations typically used in these devices; i.e., greater than 90% of the aerosol mass resided in particles less than 3.5 μm aerodynamic diameter.
Keywords: Solid lipid nanoparticles (SLN); Nanosuspensions; Water-insoluble drugs; Encapsulation; Inhalers
Solid lipid nanoparticles for targeted brain drug delivery by Paolo Blasi; Stefano Giovagnoli; Aurélie Schoubben; Maurizio Ricci; Carlo Rossi (pp. 454-477).
The present review discusses the potential use of solid lipid nanoparticles for brain drug targeting purposes. The state of the art on surfactant-coated poly(alkylcyanoacrylate) nanoparticles specifically designed for brain targeting is given by emphasizing the transfer of this technology to solid lipid matrices. The available literature on solid lipid nanoparticles and related carriers for brain drug targeting is revised as well. The potential advantages of the use of solid lipid nanoparticles over polymeric nanoparticles are accounted on the bases of a lower cytotoxicity, higher drug loading capacity, and best production scalability. Solid lipid nanoparticles physicochemical characteristics are also particularly regarded in order to address the critical issues related to the development of suitable brain targeting formulations. A critical consideration on the potential application of such technology as related to the current status of brain drug development is also given.
Keywords: CNS drug delivery; Brain targeting; Blood-brain barrier (BBB); Solid lipid nanoparticles (SLN); NLC; LDC; Polymeric nanoparticles; Polysorbate 80 (Tween® 80)
Solid lipid nanoparticles as a drug delivery system for peptides and proteins by António J. Almeida; Eliana Souto (pp. 478-490).
Solid lipid particulate systems such as solid lipid nanoparticles (SLN), lipid microparticles (LM) and lipospheres have been sought as alternative carriers for therapeutic peptides, proteins and antigens. The research work developed in the area confirms that under optimised conditions they can be produced to incorporate hydrophobic or hydrophilic proteins and seem to fulfil the requirements for an optimum particulate carrier system. Proteins and antigens intended for therapeutic purposes may be incorporated or adsorbed onto SLN, and further administered by parenteral routes or by alternative routes such as oral, nasal and pulmonary. Formulation in SLN confers improved protein stability, avoids proteolytic degradation, as well as sustained release of the incorporated molecules. Important peptides such as cyclosporine A, insulin, calcitonin and somatostatin have been incorporated into solid lipid particles and are currently under investigation. Several local or systemic therapeutic applications may be foreseen, such as immunisation with protein antigens, infectious disease treatment, chronic diseases and cancer therapy.
Keywords: Solid lipid nanoparticles; Solid lipid microparticles; Proteins; Peptides; Vaccines; Drug incorporation
Chemotherapy with anticancer drugs encapsulated in solid lipid nanoparticles by Ho Lun Wong; Reina Bendayan; Andrew M. Rauth; Yongqiang Li; Xiao Yu Wu (pp. 491-504).
The prospect of improved cancer chemotherapy using solid lipid nanoparticles (SLN) as a drug delivery system is promising. Several obstacles frequently encountered with anticancer compounds, such as normal tissue toxicity, poor specificity and stability and a high incidence of drug-resistant tumor cells, are at least partially overcome by delivering them using SLN. The emergence of the newer forms of SLN such as polymer–lipid hybrid nanoparticles, nanostructured lipid carriers and long-circulating SLN may further expand the role of this versatile drug carrier in cancer treatment. This review focuses on the current use of SLN for the encapsulation and delivery of cytotoxic anticancer compounds. It also discusses more recent trends in the use of SLN as vehicles for delivery of chemosensitizers and cytotoxic therapeutic molecules. It is anticipated that, in the near future, SLN will be further improved to deliver anticancer compounds in a more efficient, specific and safer manner.
Keywords: Abbreviations; ATRA; all-; trans; retinoic acid; AUC; area-under-the-curve; BRCP; breast cancer resistance protein; EPR; enhanced permeability and retention; 5-FU; 5-fluorouracil; FuDR; 3′,5′-dioctanoyl-5-fluoro-2′-deoxyuridine; GG918; Elacridar; hMLH1; human mutL homolog 1; LDC; lipid drug conjugate; MDR; multidrug resistance; MRP; multidrug resistance associated protein; NLC; nanostructured lipid carrier; PEG; poly[ethylene glycol]; P-gp; P-glycoprotein; PLN; polymer-lipid hybrid nanoparticles; RES; reticuloendothelial system; SLN; solid lipid nanoparticles; SN38; 7-ethyl-10-hydroxy-20(S)-camptothecinSolid lipid nanoparticles; Polymer–lipid hybrid nanoparticles; Chemotherapy; Anticancer drug delivery; Chemosensitizers; Overcoming multidrug resistance
Parasitic diseases: Liposomes and polymeric nanoparticles versus lipid nanoparticles by Abhijit A. Date; Medha D. Joshi; Vandana B. Patravale (pp. 505-521).
Parasitic diseases such as malaria, leishmaniasis, and trypanosomiasis represent a significant global burden and pose a great challenge to drug discovery and delivery scientists due to their intracellular nature and disseminated locations. Moreover, poor rate of discovery in the anti-parasitic segment seen in last few decades has necessitated effective management of existing drugs by modulating their delivery. The review focuses on the biological and biopharmaceutical issues to be considered in the design of delivery strategy for treating parasitic infections such as malaria, leishmaniasis, and trypanosomiasis. Also, it describes the role of the colloidal carriers liposomes, polymeric nanoparticles, lipid nanoparticles including lipid drug conjugate (LDC) nanoparticles in optimizing the delivery of anti-malarial, anti-leishmanial and anti-trypanosomial agents. Furthermore, the review emphasizes especially the potential of solid lipid nanoparticles (SLN) in the treatment of parasitic infections with the help of recent reports and our own experience.
Keywords: Parasitic diseases; Malaria; Leishmaniasis; Trypanosomiasis; Liposomes; Nanoparticles; Solid lipid nanoparticles (SLNs); Nanostructured lipid carriers (NLCs)
Nanostructured lipid carriers (NLC) in cosmetic dermal products by R.H. Müller; R.D. Petersen; A. Hommoss; J. Pardeike (pp. 522-530).
The first generation of lipid nanoparticles was introduced as solid lipid nanoparticles (SLN), the second, improved generation as nanostructured lipid carriers (NLC). Identical to the liposomes, the lipid nanoparticles (NLC) appeared as products first on the cosmetic market. The article gives an overview of the cosmetic benefits of lipid nanoparticles, that means enhancement of chemical stability of actives, film formation, controlled occlusion, skin hydration, enhanced skin bioavailability and physical stability of the lipid nanoparticles as topical formulations. NLC are on the market as concentrates to be used as cosmetic excipients, special formulation challenges for these products are discussed. NLC appeared also in a number of finished cosmetic products world-wide. An overview of these products is provided including their special effects due to the lipid nanoparticles, lipids used for their production and incorporated cosmetic actives.
Keywords: Lipid nanoparticles; Nanostructured lipid carriers; NLC; Cosmetic products; Skin bioavailability; NanoLipid; Nanorepair; IOPE