Development of a controlled release formulation based on SLN and NLC for topical clotrimazole delivery

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are colloidal carrier systems providing controlled release profiles for many Substances. Clotrimazole-loaded SLN and NLC were prepared by the hot high pressure homogenization technique in order to evaluate the physical stability of these particles, as well as the entrapment efficiency of this lipophilic drug and its in vitro release profile. The particle size was analyzed by PCS and LD showing that the particles remained in their colloidal state during 3 months of storage at 4, 20 and 40degreesC. For all tested formulations the entrapment efficiency was higher than 50%. The obtained results also demonstrate the use of these lipid nanoparticles as modified release formulations for lipophilic drugs over a period of 10 h

Linseed essential oil - Source of Lipids as Active Ingredients for Pharmaceuticals and Nutraceuticals

Linseed - also known as flaxseed -, is known for its beneficial effects on animal health attributed to its composition, comprising omega-6 (linoleic) and omega-3 (α-linolenic) fatty acids, various dietary fibers and lignans, which have health benefits in reducing the risk of cancer and cardiovascular diseases, lowering the levels of LDL-cholesterol and relaxing the smooth muscle cells in arteries increasing the blood flow. Essential fatty acids from flax participate in several metabolic processes of the cell, not only as structuring components of the cell membrane, but also as storage lipids. Flax is consumed in the form of seeds (whole, milled or roasted), as an oil and as flour to provide basic nutrition. Flax can be considered a functional food. Several formulations containing flax are available on the market in the form of e.g. capsules and microencapsulated powders having potential as nutraceuticals for their beneficial effects on health. This paper revises the different lipid classes found in flaxseeds and their genomics. It also discusses the beneficial effects of flax and flaxseed oil and their biological advantages as ingredients in pharmaceuticals and in nutraceuticals products.info:eu-repo/semantics/publishedVersio

Preparation of Polymeric Nanoparticles by Polymerization of Monomers - Part I

Polymeric nanoparticles obtained from synthetic polymers such as copolymers of methacrylic acid, acrylic esters or metacrylics, have been widely used in pharmaceuticals for encapsulation of drugs. These nanoparticles have the advantages of drug protection, controlled release, improved bioavailability and lower toxicity, resulting in greater comfort to patients and compliance to the treatment. The production of nanoparticles (nanospheres and nanocapsules) by polymerization of monomers is reviewed and discussed in this article, highlighting the technological parameters that affect the physicochemical characteristics of nanoparticles, e.g. drug solubility, phase volume, pH of polymerization, molecular weight and monomer concentration, and the nature and concentration of the surfactant.2219610

Comparative study between the viscoelastic behaviors of different lipid nanoparticle formulations

Application of drug substances to the skin for systemic absorption or action in a particular layer of the skin is a rather old approach. However, over the last years it has received much more attention, as a consequence of the development of new membrane-moderated and matrix reservoir devices. As new reservoir systems, solid lipid nanoparticles (SLN(TM)) and nanostructured lipid carriers (NLC(TM)) have been successfully tested for dermal application of different physicochemical substances. The knowledge obtained from theological investigations of these systems may be highly Useful for the characterization of the newly developed topical formulation. In the present study, an oscillation frequency sweep test was used for the evaluation of storage modulus (G'), loss modulus (G"), and complex viscosity (eta*) of twelve different SLN and NLC formulations, over a frequency range from 0 to 10 Hz. The lipiclic aqueous dispersions were prepared using three different solid lipids (Softisan(R)138, Compritol(R)888, and stearyl alcohol) as matrix material. Miglyol(R)812, tocopherol, sunflower oil, and long-chain triacylglycerols were the chosen liquid lipids for NLC preparation. The objective of the present work was to investigate the effect of these different liquid lipids on the theological properties of aqueous dispersions of NLC as model systems. It was found that the liquid oil component of the formulation has a strong influence on the viscoelastic parameters, which are dependent on the particle size, zeta potential, and crystallinity of the lipid particles, as well as on the solid lipid used

Evaluation of the physical stability of SLN and NLC before and after incorporation into hydrogel formulations

Aqueous dispersions of lipid nanoparticles are being investigated as drug delivery systems for different therapeutic purposes. One of their interesting features is the possibility of topical use, for which these systems have to be incorporated into commonly used dermal carriers, such as creams or hydrogels, in order to have a proper semisolid consistency. For the present investigation four different gel-forming agents (xanthan gum, hydroxyethylcellulose 4000, Carbopol(R)943 and chitosan) were selected for hydrogel preparation. Aqueous dispersions of lipid nanoparticles-solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)-made from tripalmitin were prepared by hot high pressure homogenization and then incorporated into the freshly prepared hydrogels. NLC differ from SLN due to the presence of a liquid lipid (Miglyol(R)812) in the lipid matrix. Lipid nanoparticles were physically characterized before and after their incorporation into hydrogels. By means of rheological investigations it could be demonstrated that physical properties of the dispersed lipid phase have a great impact on the rheological properties of the prepared semisolid formulations. By employing an oscillation frequency sweep test, significant differences in elastic response of SLN and NLC aqueous dispersions could be observed

Epigallocatechin-3-gallate PEGylated poly(lactic-co-glycolic) acid nanoparticles mitigate striatal pathology and motor deficits in 3-nitropropionic acid intoxicated mice

AIM:To compare free and nanoparticle (NP)-encapsulated epigallocatechin-3-gallate (EGCG) for the treatment of Huntington’s disease (HD)-like symptoms in mice. MATERIALS & METHODS: EGCG was incorporated into PEGylated poly(lactic-co-glycolic) acid NPs with ascorbic acid (AA). HD-like striatal lesions and motor deficit were induced in mice by 3-nitropropionic acid-intoxication. EGCG and EGCG/AA NPs were co-administered and behavioral motor assessments and striatal histology performed after 5 days. RESULTS: EGCG/AA NPs were significantly more effective than free EGCG in reducing motor disturbances and depression-like behavior associated with 3-nitropropionic acid toxicity. EGCG/AA NPs treatment also mitigated neuroinflammation and prevented neuronal loss. CONCLUSION: NP encapsulation enhances therapeutic robustness of EGCG in this model of HD symptomatology. Together with our previous findings, this highlights the potential of EGCG/AA NPs in the symptomatic treatment of neurodegenerative diseases

Dual-drug loaded nanoparticles of Epigallocatechin-3-gallate (EGCG)/Ascorbic acid enhance therapeutic efficacy of EGCG in a APPswe/PS1dE9 Alzheimer's disease mice model

Epigallocatechin-3-gallate (EGCG) is a candidate for treatment of Alzheimer's disease (AD) but its inherent instability limits bioavailability and effectiveness. We found that EGCG displayed increased stability when formulated as dual-drug loaded PEGylated PLGA nanoparticles (EGCG/AA NPs). Oral administration of EGCG/AA NPs in mice resulted in EGCG accumulation in all major organs, including the brain. Pharmacokinetic comparison of plasma and brain accumulation following oral administration of free or EGCG/AA NPs showed that, whilst in both cases initial EGCG concentrations were similar, long-term (5–25 h) concentrations were ca. 5 fold higher with EGCG/AA NPs. No evidence was found that EGCG/AA NPs utilised a specific pathway across the blood-brain barrier (BBB). However, EGCG, empty NPs and EGCG/AA NPs all induced tight junction disruption and opened the BBB in vitro and ex vivo. Oral treatment of APPswe/PS1dE9 (APP/PS1) mice, a familial model of AD, with EGCG/AA NPs resulted in a marked increase in synapses, as judged by synaptophysin (SYP) expression, and reduction of neuroinflammation as well as amyloid β (Aβ) plaque burden and cortical levels of soluble and insoluble Aβ(1-42) peptide. These morphological changes were accompanied by significantly enhanced spatial learning and memory. Mechanistically, we propose that stabilisation of EGCG in NPs complexes and a destabilized BBB led to higher therapeutic EGCG concentrations in the brain. Thus EGCG/AA NPs have the potential to be developed as a safe and strategy for the treatment of AD

Development and optimisation of spironolactone nanoparticles for enhanced dissolution rates and stability

Stable solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) formulations to enhance the dissolution rates of poorly soluble drug spironolactone (SP) were being developed. Probe ultra-sonication method was used to prepare SLNs and NLCs. All NLCs contained stearic acid (solid lipid carrier) and oleic acid (liquid lipid content), whereas, SLNs were prepared and optimised by using the solid lipid only. The particles were characterised in terms of particle size analysis, thermal behaviour, morphology, stability and in vitro release. The zeta sizer data revealed that the increase in the concentration of oleic acid in the formulations reduced the mean particle size and the zeta potential. The increase in concentration of oleic acid from 0 to 30% (w/w) resulted in a higher entrapment efficiency. All nanoparticles were almost spherically shaped with an average particle size of about ∼170 nm. The DSC traces revealed that the presence of oleic acid in the NLC formulations resulted in a shift in the melting endotherms to a higher temperature. This could be attributed to a good long-term stability of the nanoparticles. The stability results showed that the particle size remained smaller in NLC compared to that of SLN formulations after 6 months at various temperatures. The dissolution study showed about a 5.1- to 7.2-fold increase in the release of the drug in 2 h compared to the raw drug. Comparing all nanoparticle formulations indicated that the NLC composition with a ratio of 70:30 (solid:liquid lipid) is the most suitable formulation with desired drug dissolution rates, entrapment efficiency and physical stability

Comparative Anatomical Analyses of the Forearm Muscles of Cebus libidinosus (Rylands et al. 2000): Manipulatory Behavior and Tool Use

The present study describes the flexor and extensor muscles in Cebus libidinosus' forearm and compares them with those from humans, chimpanzees and baboons. The data is presented in quantitative anatomical indices for similarity. The capuchin forearm muscles showed important similarities with chimpanzees and humans, particularly those that act on thumb motion and allow certain degree of independence from other hand structures, even though their configuration does not enable a true opposable thumb. The characteristics of Cebus' forearm muscles corroborate the evolutionary convergence towards an adaptive behavior (tool use) between Cebus genus and apes