Microneedles as transdermal delivery systems: combination with other enhancing strategies.

Transdermal drug delivery has exhaustively been studied over the past decades due to its multiple advantages over other administration routes; however, drugs that can be administered by this via are few owe to the stratum corneum permeability properties. Recently, several strategies to bypass the upper-layer skin barrier have been developed. One of the latest advances in this area has been the use of micro-scale needles, which painlessly pierce skin, increasing the passage of drugs with unfavourable skin permeability (i.e., low potent, hydrophilic, high molecular drugs) by several orders of magnitude, by bypassing the stratum corneum. Microneedles have shown to be safe and easy-to-use for drug administration, a nouvelle alternative to hypodermic needle injections, and an array in which drugs can be included to attain a controlled release as to achieve a higher drug delivery. Several works have demonstrated that such devices dramatically increase transdermal delivery of large molecules, thus nowadays microneedles have been regarded as a potential technology approach to be employed alone or with other enhancing methods such as electroporation and iontophoresis, as well as with different drug carriers (e.g., lipid vesicles, micro- and nanoparticles). Hence, this review is mainly focused on presenting the results obtained when combining microneedles with a variety of strategies to ease drug diffusion through skin, including physical enhancers and drug carrier systems.

Residues of organochlorine pesticides in soils from the southern Sonora, Mexico.

Although, the Yaqui and Mayo valleys are the most important agricultural areas in Sonora, there is only limited data of the pesticides residue in soils in these valleys. This study measured the organochlorine pesticides (OCPs) in 234 soil samples (residential and agricultural) from 24 communities. The global results (mean, range) indicated that benzene hexachloride (19.2, ND-938.5 µg g(-1)), endrin (6.6, ND-377.3 µg g(-1)) and DDTs (36.45, ND-679.7 µg g(-1)) were the dominant contaminants. Soil is one of the most important routes of exposure to OCPs in the population of southern Sonora and this study can be used to establish background levels of OCPs.

Determination of poloxamer 188 and poloxamer 407 using high-performance thin-layer chromatography in pharmaceutical formulations.

Poloxamers (PXMs) are amphiphilic non-ionic block polymers commonly used in the cosmetic and pharmaceutical industries. In spite of the wide use of PXMs, few studies have dealt with the analysis of these polymers in pharmaceutical preparations. In this work, high-performance thin-layer chromatography (HPTLC) has been used to quantify both PXM-188 and PXM-407 in pharmaceutical preparations. The separation of these compounds was carried out using reverse phase HPTLC plates with a chloroform-methanol mixture as the mobile phase. Detection was performed densitometrically using the Dragendorff's reagent for the visualization of PXMs. Quality parameters were established, and the detection limits ranged from 24 to 47ng/spot. A good precision (day to day and run to run), with relative standard deviations <11.18%, was obtained. The proposed method was satisfactorily applied to the analysis of laboratory-made and commercial pharmaceutical products.

Skin permeation enhancement by sucrose esters: a pH-dependent phenomenon.

The purpose of the present study was to evaluate the effect of sucrose esters (particularly, sucrose laureate and sucrose oleate in Transcutol) on the percutaneous penetration of a charged molecule as a function of ionization. We have investigated the influence of these sucrose esters on the in vitro diffusion profiles of lidocaine hydrochloride, a weak ionizable base (pKa=7.9), at different pH values, using porcine ear skin as the barrier membrane. As expected, lidocaine flux in the absence of an enhancer, increased from pH 5 to 9 with a corrresponding increase in the level of the unionized base. However, when skin was pretreated with 2% laureate in Transcutol (2% L-TC), drug permeation was higher at pH 5.0 and 7.0 than at 9.0. A different trend was observed in experiments with 2% oleate in Transcutol (2% O-TC), where skin flux was maximal at a more basic pH, when the degree of ionization is low. The results suggest that sucrose laureate enhances the penetration of the ionized form of the drug (12-fold greater flux relative to control), whereas sucrose oleate is more effective in promoting permeation of the unionized species. The structural properties of the sucrose esters as well as the degree of ionization of the drug are important characteristics affecting the transdermal flux of lidocaine.

Assessment of the in vitro and in vivo biological activities of the human follicle-stimulating isohormones.

Gonadotropins are synthesized and released in different molecular forms. In this article, we present evidence that the glycosylation variants of human pituitary FSH exhibit differential and divergent effects at the target cell level and that less sialylated, short-lived variants may exert significant effects in in vivo conditions. Less acidic/sialylated glycoforms (elution pH value 6.60-4.60 as disclosed by high resolution chromatofocusing of anterior glycoprotein extracts), induced higher cAMP release, estrogen production and tissue-type plasminogen activator (tPA) enzyme activity as well as cytochrome P450 aromatase and tPA mRNA expression in cultured rat granulosa cells than the more acidic analogs (pH<4.76). By contrast, the more acidic/sialylated glycoforms induced higher alpha-inhibin subunit mRNA expression than their less acidic counterparts. In cumulus enclosed oocytes isolated from mice ovaries, addition of less acidic isoforms induced resumption of meiosis more efficiently than the more acidic analogs. Interestingly, the least acidic isoform (pH>7.10) behave as a strong antagonist of several FSH-mediated effects. Assessment of the in vivo effects of the isoforms on granulosa cell proliferation in follicles from immature rats, revealed that short-lived isoforms were equally or even more efficient than their more acidic counterparts in maintaining granulosa cell proliferation when administered immediately after hypophysectomy. These results show that the naturally occurring human FSH isoforms may exhibit differential or even unique effects at the target cell level and that factors other than the metabolic clearance rate of the molecule (including receptor-binding affinity and capability of the ligand to activate its receptor and trigger intracellular signaling) also play an important role in determining the net in vivo effects of a particular FSH variant.

[Wood anatomy and uses of 7 tropical tree species from Mexico]. / Anatomía y usos de la madera de siete árboles tropicales de México.

The wood anatomy of Coccoloba cozumelensis Hemsl., Coccoloba spicata Lundell, Gymnanthes lucida Sw., Blomia cupanioides Miranda, Canella winterana (L.) Gaertn., Aspidosperma megalocarpon Müell Arg. and Ehretia tinifolia L., is described. One tree per species was collected in the tropical rain forest of Quintana Roo, Mexico. Their wood has important traditional uses in furniture, tools, rural buildings, posts, fences, railroads and firewood. Macroscopic and microscopic characteristics were described and measured in wood samples, permanent slides and macerated material. These species have diffuse porosity, alternate vessel pits, simple perforation plates, numerous and small rays; libriform fibres are common, as well as ergastic material in gum forms, calcium carbonate and silica crystals. These characteristics explain aesthetical, weight, hardness and resistance (to mechanical and biological damage) characters that fit traditional use by the Maya.