Lipid nanoparticles for skin penetration enhancement-correlation to drug localization within the particle matrix as determined by fluorescence and parelectric spectroscopy.

With topical treatment of skin diseases, the requirement of a high and reproducible drug uptake often still is not met. Moreover, drug targeting to specific skin strata may improve the use of agents which are prone to cause local unwanted effects. Recent investigations have indicated that improved uptake and skin targeting may become feasible by means of nanoparticular systems such as solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions (NE). Here we describe techniques to characterize drug loading to carrier systems and skin penetration profiles by using the lipophilic dye nile red as a model agent. Since the mode of drug association with the particle matrix may strongly influence the efficiency of skin targeting, parelectric spectroscopy (PS) was used to differentiate between matrix incorporation and attachment to the particle surface and fluorescence spectroscopy (FS) to solve dye distribution within NLC particles. Nile red was incorporated into the lipid matrix or the covering tensed shell, respectively, of SLN and NLC with all the lipids studied (Compritol, Precirol, oleic acid, Miglyol). In NLC, the dye was enriched in the liquid phase. Next, nile red concentrations were followed by image analysis of vertical sections of pigskin treated with dye-loaded nanoparticular dispersions and an oil-in-water cream for 4 and 8 h in vitro. Following the SLN dispersions, dye penetration increased about fourfold over the uptake obtained following the cream. NLC turned out less potent (相似文献   

Botulinum toxin and medical liability: is the patient sufficiently informed?]

INTRODUCTION: The use of botulinum toxin injection therapy is soaring significantly today, with an ever-wider field of applications despite well-known side effects of the treatment. This article aims at analysing the medicolegal practices of practitioners who use this therapy, especially the information given to patients and finding a common practice for providing that information. METHODS: We sent a questionnaire to 340 practitioners who might use the therapy (physiatrists, neurologists, ophthalmologists, ENT specialists, plastic surgeons) working in hospitals and in physical therapy and rehabilitation centres in France. Besides mentioning the possible side effects of the therapy, the questionnaire focused on how such information was transmitted before the injection. RESULTS: Data collection and analysis were performed by use of a spreadsheet software programme. A total of 124 questionnaires were analysed. We did not analyse the items dealing with side effects. Sixty-five percent of the responders said they did not seek statutory authorisation for injections. Only 31% provided written, detailed information and 12% required a signed consent form. Complaints were rare, approximately 12%, were written or verbal, and were always dismissed. DISCUSSION: Side effects after botulinum toxin injection are clearly described in the medical literature. Therefore, it is of utmost importance for this product to be used therapeutically and only by experienced therapists who will carefully respect the product's standard rules of use and inform their patients to the best of their ability. Issuing a detailed letter of information describing all the side effects seems necessary. We suggest a model information letter such as that provided to the patients in our facility. CONCLUSION: Botulinum toxin is a very worthwhile product for numerous abnormalities but has side effects, often brief, at the site of the injection. Therefore it is our duty to inform patients effectively.     

C-reactive protein, leukocyte count and D-dimer monitoring after orthopedic surgery: early diagnosis of infectious or thromboembolic complications. Part two: does d-dimer measurement contribute to the diagnosis of postoperative venous thromboembolism?]

OBJECTIVES: To determine the modification in postoperative D-dimer level as a function of the surgical act and to assess the relevance of this measure for diagnosing thromboembolism. METHOD: A cohort of 179 patients was followed: group 1 comprised 128 patients undergoing lower limb arthroplasty, group 2 comprised 29 patients undergoing lower limb surgery without implant, and group 3 comprised 22 patients undergoing spinal or upper limb surgery. D-dimer level was systematically measured on admission and then once a week for 4 weeks. Doppler ultrasonography was performed on clinical suspicion of deep vein thrombosis. D-dimer levels were compared between patients with and without deep vein thrombosis. RESULTS: D-dimer levels were constantly elevated postsurgery (2- to 6-fold above normal) and returned to normal by week 4 in groups 2 and 3 but remained elevated in group 1 (3-fold above normal). Deep vein thrombosis was suspected in 45 cases and confirmed by Doppler ultrasonography in 10 cases. D-dimer level was not significantly different between patients with deep vein thrombosis and those without. DISCUSSION AND CONCLUSIONS: In the postoperative period, measurement of D-dimer level does not aid in diagnosing thromboembolism since its constant high level obviates any negative predictive value.     

Preferential liver gene expression with polypropylenimine dendrimers.

Previously, the lower generation (DAB 8-generation 2 and DAB 16-generation 3) polypropylenimine dendrimers have been shown to be effective gene delivery systems in vitro. In the current work, we sought to: (a) test the effect of the strength of the carrier, DNA electrostatic interaction on gene transfer and (b) to study the in vivo gene transfer activity of these low molecular weight (<1687 Da) non-amphiphilic plain and quaternary ammonium gene carriers. Towards this aim, methyl quaternary ammonium derivatives of DAB 4 (generation 1), DAB 8, DAB 16 and DAB 32 (generation 4) were synthesised to give Q4, Q8, Q16 and Q32, respectively. Quaternisation of DAB 8 proved to be critical in improving DNA binding, as evidenced by data from the ethidium bromide exclusion assay and dendrimer-DNA colloidal stability data. This improved colloidal stability had a major effect on vector tolerability, as Q8-DNA formulations were well tolerated on intravenous injection while a similar DAB 8-DNA dose was lethally toxic by the same route. Quaternisation also improved the in vitro cell biocompatibility of DAB 16-DNA and DAB 32-DNA dendrimer complexes by about 4-fold but not that of the lower generation DAB 4-DNA and DAB 8-DNA formulations. In contrast to previous reports with non-viral gene delivery systems, the intravenous administration of DAB 16-DNA and Q8-DNA formulations resulted in liver targeted gene expression as opposed to the lung targeted gene expression obtained with the control polymer-Exgen 500 [linear poly(ethylenimine)] and a lung avoidance hypothesis is postulated. We conclude that the polypropylenimine dendrimers are promising gene delivery systems which may be used to target the liver and avoid the lung and also that molecular modifications conferring colloidal stability on gene delivery formulations have a profound effect on their tolerability on intravenous administration.     

Cyclodextrin formulation of dorzolamide and its distribution in the eye after topical administration.

Due to limited aqueous solubility of dorzolamide at physiologic pH, the pH of Trusopt eye drops (cont. 2% dorzolamide) has to be kept at about 5.65, and to increase the topical bioavailability of the drug from Trusopt the contact time of the drug with the eye surface is increased by increasing the viscosity of the eye drops to 100 cps. This low pH and high viscosity can lead to local irritation. In this study, dorzolamide hydrochloride was formulated as 2% and 4% low viscosity solutions (viscosity 3 to 5 cps) containing randomly methylated beta-cyclodextrin at pH 7.45. These formulations were evaluated in rabbits. The animals were sacrificed at various time points after topical administration of the drug and the dorzolamide concentration determined in the different parts of the eye. Trusopt was used as a reference standard. The topical availability of dorzolamide from the cyclodextrin-containing eye drops appeared to be comparable to that from Trusopt and the drug reached retina and optic nerve to give measurable concentrations for at least 8 h after administration of the eye drops.     

Electron beam therapy for eyelid carcinomas

Forty-six (85%) basal cell and eight (15%) squamous cell carcinomas of the eyelids were treated with electron beams between 1963 and 1983. Lesion sizes ranged from microscopic to 4 cm, with 28 lesions larger than 1 cm. Thirty-eight lesions were treated with radiotherapy after incisional biopsy, and 16 were treated after excisional biopsy (specimens showed positive margins). Doses varied from 45 to 72 Gy, with daily fractions ranging from 2.12 to 4.0 Gy. There were six disease recurrences (10.9%): three in the treatment field and three at the treatment margin. Four of six recurrences were subsequently controlled by limited surgical excision and repair with preservation of the eye, whereas the other two required enucleation. Treatment sequelae such as skin atrophy, telangiectasis, and cosmetic results were evaluated in terms of radiotherapy parameters, pretreatment surgery, and size of the lesion. In 44 patients, the overall cosmetic result was judged as good to excellent, five patients had a mild to modest degree of deformity, and five had significant deformity. Such deformity was usually associated with tumor destruction or previous surgery. No major complications were noted.