Effects of rufloxacin in Salmonella typhimurium infection in mice.

This study was undertaken to investigate the efficacy of rufloxacin, a new quinolone which is interesting due to its pharmacokinetics characterized by a long plasma half-life, in the treatment of systemic salmonella infections in the mouse typhoid model. Innately susceptible BALB/c and resistant CBA mice were used to investigate the efficacy of rufloxacin in controlling systemic salmonella infections when given for brief or prolonged periods. The present study shows that rufloxacin is not only very effective on both mouse strains, but can completely eradicate the salmonellae from livers and spleens when given early in the infection of CBA resistant mice.     

Modern drug delivery strategies applied to natural active compounds

Introduction: Colloidal drug delivery systems (CDDSs) are innovative carriers that have been studied in pharmaceutical field from many years to overcome unfavorable physical and chemical features of synthetic drugs. Recently the use of CDDS as carriers for phytochemicals has seen an exponential increase which, in some cases, has led to the rediscovery of ancient and forgotten natural molecules.

Area covered: This article focuses on the main features of CDDS, particularly micro- and nanoemulsions, vesicular carriers and micro- and nanoparticles, loaded with natural active compounds. A detailed review of the literature is presented, introducing the importance of these systems in terms of their capability to optimize the stability of phytochemicals, their absorption through biological membranes and their bioavailability.

Expert opinion: The delivery of phytochemicals is problematic due to poor solubility, poor permeability, low bioavailability, instability in biological milieu and extensive first-pass metabolism. Global research efforts investigating nanotechnology have attempted to overcome these limitations rediscovering and, in some cases, ‘discovering ex novo’ unexpected virtues and benefits associated to these compounds. The ‘nanotechnological approach’ can definitely enhance the pharmacokinetics and therapeutic index of natural active compounds and improve their performance in therapy.     

Evaluation of in-vivo topical anti-inflammatory activity of indometacin from liposomal vesicles

The aim of this study was to evaluate the in-vivo drug release profile of indometacin-loaded liposomes into the skin. Large unilamellar vesicles (LUVs), composed of dipalmitoyl-L-alpha-phosphatidylcholine and cholesterol (9:1), were obtained using the extrusion method and then incorporated in hydrogels (LUV-A and LUV-B). The delivery of indometacin from the liposomal system was evaluated by determining its in-vivo local anti-inflammatory activity after cutaneous application of liposomal gel formulations; the anti-inflammatory activity is directly proportional to the amount of drug that actually crosses the skin. UVB-induced erythema on healthy human volunteers was chosen as the inflammatory model and the extent of erythema was monitored by the non-invasive technique of reflectance spectrophotometry. The results showed that LUV dispersions containing indometacin provided a high percentage of entrapped drug (approximately 84%). Furthermore, in-vivo findings revealed that the anti-inflammatory effect was more prolonged when indometacin was delivered from a liposomal gel formulation rather than from a gel formulation without liposomes. In particular, the indometacin-loaded gel formulation LUV-A showed a sustained effect, probably related to an interaction between LUV lipids and stratum corneum lipid structure. This interaction produces a depot in the stratum corneum that ensures sustained release of the drug to deeper skin layers.     

Role of Salmonella enteritidis lipopolysaccharide on anti-HSV activity of macrophages from different anatomical sites

It is generally agreed that endotoxins from Gram-negative bacteria play a modulatory role on several macrophage functions. The intrinsic activity versus herpes simplex virus type 1 and type 2 of Kupffer cells, peritoneal and alveolar macrophages, harvested from normal and tumour-bearing rats, was evaluated. Moreover, the effects of different intravenous treatments with S. enteritidis endotoxin were investigated. The antiviral activity of peritoneal, alveolar macrophages and Kupffer cells from tumour-bearing rats is definitely impaired but it appears to be positively modulated by in-vivo administration of S. enteritidis lipopolysaccharide (LPS).     

Evaluation of percutaneous absorption of the repellent diethyltoluamide and the sunscreen ethylhexyl p‐methoxycinnamate‐loaded solid lipid nanoparticles: an in‐vitro study

Objectives Diethyltoluamide and ethylhexyl p‐methoxycinnamate (OMC) are two active ingredients in insect repellent and sunscreen products, respectively. The concurrent application of these two substances often increases their systemic absorption, compromising the safety and efficiency of the cosmetic product. In this study, diethyltoluamide and OMC were incorporated into solid lipid nanoparticles, a colloidal drug delivery system, to reduce percutaneous absorption and avoid toxic effects and also maintain the efficacy of the two active compounds on the skin surface for a long duration. Methods Solid lipid nanoparticles were prepared based on an ultrasonication technique and characterized by differential scanning calorimetry (DSC) analyses. In‐vitro studies determined the percutaneous absorption of diethyltoluamide and OMC. Key findings DSC data carried out on unloaded and diethyltoluamide‐ and/or OMC‐loaded solid lipid nanoparticles highlighted that diethyltoluamide and OMC modified the temperature and the enthalpy change associated to the calorimetric peak of solid lipid nanoparticles. The concurrent presence of the two compounds in the solid lipid nanoparticles caused a synergic effect, indicating that the lipid matrix of nanoparticles guaranteed a high encapsulation of both diethyltoluamide and OMC. Results from the in‐vitro study demonstrated that the particles were able to reduce the skin permeation of the two cosmetic ingredients in comparison with an oil‐in‐water emulsion. Conclusions This study has provided supplementary evidence as to the potential of lipid nanoparticles as carriers for topical administration of cosmetic active compounds.     

Naproxen 1-Alkylazacycloalkan-2-one esters as dermal prodrugs: in vitro evaluation

1-Alkylazacycloalkan-2-one esters of naproxen were synthesized and assayed to determine their stability in phosphate buffer and isopropyl myristate, susceptibility to undergoing in vitro enzymatic hydrolysis and flux through excised human skin. 1-Methylazacycloalkan-2-one esters of naproxen (I–IV) proved poorly stable both in aqueous media and isopropylmyristate while 1-ethylazacycloalkan-2-one esters (V–VIII) were much more stable. Esters V–VIII were readily hydrolyzed in vitro by porcine esterase and esters V–VI penetrated excised human skin better than the parent drug from aqueous suspensions. On the basis of the results obtained, 1-ethylpyrrolidone and 1-ethylvalerolactam appear to be suitable promoieties for obtaining naproxen dermal prodrugs.     

Synthesis and pharmacologic activity of 2-arylethenylthiazol-4-acetic and 4-carboxylic acids

Two new series of 2-aryletenylthiazolo-4-acetic (IV-XII) and 4-carboxylic (XIII-XXI) acids substituted with alkoxy groups in the benzene ring were synthesized. The compounds were subjected to comparative tests of antiinflammatory, analgesic and antipyretic activity.     

Vehicle effects on in vitro skin permeation of and stratum corneum affinity for model drugs caffeine and testosterone

The effects of Labrasol (LBS) (glycolysed ethoxylated C₈/C₁₀ glycerides), Labrafil (LBF) (glycolysed ethoxylated glycerides), Transcutol (TSC) (diethylene glycol monoethyl ether) and DPPG (propylene glycol dipelargonate) on the flux across excised human skin of the lipophilic testosterone (TST) and the hydrophilic caffeine (CAF) and on the affinity of the human stratum corneum for these drugs are compared taking propylene glycol (PG) and liquid petrolatum (LP) as reference vehicles. DPPG and LBF enhance CAF flux relative to PG while LBS and TSC increase the stratum corneum affinity for TST relative to LP. However, the materials tested enhance neither the flux of nor the stratum corneum affinity for both drugs with respect to either reference. On the other hand, a saturated solution of DPPG in PG enhances both properties for both drugs relative to PG. Such effects are ascribed to the ability of DPPG to interact with the lipid bilayers and to that of PG to promote DPPG penetration into stratum corneum and to create interaction sites in such a tissue.     

Antiallergic and antihistaminic effect of two extracts of Capparis spinosa L. flowering buds

The antiallergic properties of two lyophilized extracts obtained from Capparis spinosa L. flowering buds (capers) by methanol extraction, carried out at room temperature (CAP-C) or with heating at 60 degrees C (CAP-H), were investigated.The protective effects of CAP-H and CAP-C, orally administered (14.28 mg[sol ]kg), were evaluated against Oleaceae antigen challenge-induced and histamine-induced bronchospasm in anaesthetized guinea-pigs. Furthermore, the histamine skin prick test was performed on humans, applying a gel formulation containing 2% CAP-C (the only extract able to protect against histamine-induced bronchospasm) on the skin for 1 h before histamine application and monitoring the erythema by reflectance spectrophotometry.The CAP-H showed a good protective effect against the bronchospasm induced by antigen challenge in sensitized guinea-pigs; conversely, a significant decrease in the responsiveness to histamine was seen only in CAP-C pretreated animals. Finally, the CAP-C gel formulation possessed a marked inhibitory effect (46.07%) against histamine-induced skin erythema.These two caper extracts displayed marked antiallergic effectiveness; however, the protective effect of CAP-H was very likely due to an indirect mechanism (for example, inhibition of mediator release from mast cells or production of arachidonic acid metabolites); conversely, CAP-C is endowed with direct antihistaminic properties. The different mechanisms of action of CAP-H and CAP-C may be related to a difference in the extraction procedure and, thus, in their qualitative[sol ]quantitative chemical profile.     

Characterization of indomethacin-loaded lipid nanoparticles by differential scanning calorimetry

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) are interesting nanoparticulate delivery systems produced from solid lipids. Both carrier types are submicron size particles but they can be distinguished by their inner structure. In the present paper, indomethacin (IND)-loaded SLN and NLC were prepared and the organization and distribution of the different ingredients originating each type of nanoparticle system were studied by differential scanning calorimetry (DSC) technique. Furthermore, mean particle size and percentage of drug encapsulation were also determined. From the results obtained, NLC lipid organization guaranteed an increased indomethacin encapsulation in comparison with SLN. DSC static and dynamic measurements performed on SLN and NLC showed that oil nanocompartments incorporated into NLC solid matrix drastically influenced drug distribution inside the nanoparticle system. Controlled release from NLC system could be explained considering both drug partition between oil nanocompartments and solid lipid and a successive partition between solid lipid and water.