Quantification of 5-FU in skin samples for the development of new delivery systems for topical cancer treatment.

5-Fluorouracil (5-FU) is used for the topical treatment of pre-cancerous skin lesions. However, previous reports focus on 5-FU quantification in plasma samples, failing to provide information about drug quantification in the skin. Therefore, the aim of this work was to develop a simple and reliable analytical method employing HPLC-UV for 5-FU quantification in skin samples. Chromatographic separation was obtained using the commonly available Lichrospher RP-C18 endcapped column. Porcine ear skin matrix-based analytical curves with thymine, as internal standard, were used. 5-FU was eluted at 5.2 min and thymine at 13.0 min. The method was selective, precise and accurate in the linear range from 0.3 to 6 µg/mL. The samples were stable after three cycles of freeze/thawing and extraction efficiency rates above 95% were obtained. In vitro skin penetration studies of an aqueous solution and a commercial cream of 5-FU were performed. The cream improved 5-FU retention into the skin and permeation through the skin compared to the solution. Therefore, the method developed herein can be applied to the study of formulations for topical delivery of 5-FU.

Excised porcine cornea integrity evaluation in an in vitro model of iontophoretic ocular research.

BACKGROUND/AIMS: It is a challenge to adapt traditional in vitro diffusion experiments to ocular tissue. Thus, the aim of this work was to present experimental evidence on the integrity of the porcine cornea, barrier function and maintenance of electrical properties for 6 h of experiment when the tissue is mounted on an inexpensive and easy-to-use in vitro model for ocular iontophoresis. METHODS: A modified Franz diffusion cell containing two ports for the insertion of the electrodes and a receiving compartment that does not need gassing with carbogen was used in the studies. Corneal electron transmission microscopy images were obtained, and diffusion experiments with fluorescent markers were performed to examine the integrity of the barrier function. The preservation of the negatively charged corneal epithelium was verified by the determination of the electro-osmotic flow of a hydrophilic and non-ionized molecule. RESULTS: The diffusion cell was able to maintain the temperature, homogenization, porcine epithelial corneal structure integrity, barrier function and electrical characteristics throughout the 6 h of permeation experiment, without requiring CO(2) gassing when the receiving chamber was filled with 25 mM of HEPES buffer solution. CONCLUSION: The system described here is inexpensive, easy to handle and reliable as an in vitro model for iontophoretic ocular delivery studies.

Iontophoretic delivery of 5-aminolevulinic acid (ALA): effect of pH.

PURPOSE: To examine the iontophoretic delivery of ALA as a function of pH and to determine the principal mechanisms responsible for its electrotransport. METHODS: Anodal iontophoretic transport of ALA was measured as a function of its concentration and pH of the donor solution. Experiments were performed in vitro using skin excised from porcine ears as the membrane. To deduce mechanism, the concomitant transport of the electroosmotic marker, mannitol, was also assessed. RESULTS: ALA iontophoresis at pH 7.4 is a linear function of concentration over the range 1-100 mM. The mechanism was deduced to be electroosmosis. By reducing the pH from 7.4 to 4.0, the dominant mechanism of ALA transport was shifted from electroosmosis to electrorepulsion as the skin's net negative charge was progressively neutralized. However, the total delivery of the compound was not altered by lowering the pH suggesting that the increased electrorepulsive contribution was essentially balanced by the concomitantly reduced electroosmosis. CONCLUSIONS: Significant ALA delivery at pH 7.4 can be achieved by increasing the drug concentration in the anodal formulation to 100 mM. Lowering the pH does not result in increased ALA transport. Alternative strategies are therefore required to maximize and optimize ALA delivery by iontophoresis.

Influence of cyclodextrin complexation on the in vitro permeation and skin metabolism of dexamethasone.

The influence of complexation of a model drug, dexamethasone acetate (DMA), with beta-cyclodextrin (beta-CyD) and hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) on the in vitro permeation through hairless mouse skin and on skin metabolism have been investigated. Complexation with CyDs increased the amount of DMA permeated in the order of 2.0 and 3.0 times for beta-CyD and HP-beta-CyD, respectively. The partition coefficient, between stratum corneum and buffer (K(SC/buffer)), for DMA decreased when the drug was an inclusion complex, being greatest for DMA/HP-beta-CyD complex. Complexation protected the drug against skin metabolism. The increase of skin permeation and stability of the model drug in the skin suggest that the complexation with beta-CyD and HP-beta-CyD is a rational way to improve the physical-chemical properties of drugs for use in transdermal delivery systems.

Clinical health problem: failure to thrive.

Families in which NOFTT is present need interventions that target behaviors and identify stressors that contribute to decreased caloric intake. A holistic approach to the situation is required, to deal with considering the problem which may stem from multiple sources. Maternal perceptions of health and diet can be influenced by the practitioner in a sensitive manner, encouraging balance. Infant feeding difficulties can be identified by the practitioner and appropriate referrals can be made to FTT clinics that are experienced in working with these infants and their caregivers. Public health nurses can be utilized to further assess families, follow up on health teaching, and provide referrals to community resources to alleviate stressors. Management of NOFTT by a practitioner in the primary care setting is feasible and cost-effective.

Reflex sympathetic dystrophy. Timely diagnosis and treatment can prevent severe contractures.

Reflex sympathetic dystrophy is a clinical syndrome consisting of persistent burning pain and varying degrees of vasomotor and trophic changes in an extremity after trauma. Although several mechanisms have been proposed, none have been universally accepted. Historically, treatment has involved sympathetic blockade or sympathectomy to prevent the proposed sympathetic hyperactivity. However, only a limited number of controlled studies have been conducted, and results have been controversial. The cornerstone of treatment is physical therapy to prevent the severe contractures that can result.

Spirocamallanus rebecae sp. n. (Nematoda: Camallanidae) from freshwater fishes in south-eastern Mexico.

Spirocamallanus rebecae sp. n. is described from freshwater cichlids in some lakes of Southeast Mexico. It has 14 spiral bands in the buccal capsule, similar unequal spicules 503-544 and 281-297 long, 3 precloacal and 6 postcloacal pairs of papillae, vulva situated in the middle part of the body. An updated list of the species of the genus is presented.