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Transdermal Penetration (transdermal + penetration)
Selected AbstractsIn-vitro transdermal penetration of cytarabine and its N4-alkylamide derivativesJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2010Lesetja J. Legoabe Abstract Objectives The aim of this study was to synthesise and determine the transdermal penetration of cytarabine alkylamide derivatives and assess the correlation of flux with physicochemical properties. Methods The alkylamide derivatives of cytarabine were synthesised by acylation at the N4-amino group by the mixed anhydride method. The in-vitro permeation studies were performed using the Franz diffusion cell methodology. Furthermore, partition coefficients (n -octanol,water) and aqueous solubility of the N4-alkylamide derivatives of cytarabine were determined in order to obtain information about their lipophilicity and hydrophilicity. Key findings The N4-alkylamides of cytarabine (acetyl, butanoyl, hexanoyl, octanoyl, and decanoyl derivatives) showed decreased hydrophilicity and increased lipophilicity. The log D values of the alkylamides were higher than that of the parent compound and increased linearly as the alkyl chain lengthened. N4-hexanoyl-4-amino-1-[(2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl] pyrimidin-2-one) showed the highest median steady-state flux (Jss) of 89.0 nmol/cm2 per h in the series, which shows a high statistical difference with the parent compound flux value (3.70 nmol/cm2 per h). Conclusions The prodrug approach appears to be a promising strategy for the enhancement of transdermal penetration of cytarabine. [source] Synthesis and hydrolytic behaviour of 2-mercaptoethyl ibuprofenate,polyethylene glycol conjugate as a novel transdermal prodrugJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2003Soodabeh Davaran ABSTRACT Thiolated derivatives of ibuprofen and its polyethylene glycol ester were synthesized via condensation of 2-mercaptoethyl ibuprofenate with carboxy-terminated polyethylene glycol. The release of ibuprofen from this polymeric prodrug has been studied under conditions simulating those encountered in the skin. The polymeric prodrug of ibuprofen was found to undergo pH-dependent hydrolysis, ranging from negligible hydrolysis at pH 4 to 23.9% hydrolysis at pH 8.5 (15% at pH 7.4) after 48 h at 37 °C. The polymer,drug conjugate was subjected to enzymatic hydrolysis in human plasma. The polymer showed considerable enzymatic hydrolysis (68% after 48 h). The results showed that the polymeric prodrug model of non-steroidal anti-inflammatory drugs (NSAIDs) described here can be used in topical formulations of NSAIDs. It is expected that the novel thiol derivative will have both enhanced transdermal penetration and stability to oxidation which make it a suitable candidate for transdermal formulations. [source] The effects of freezing skin on transdermal drug penetration kineticsJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2007L. A. AHLSTROM This study investigated the effects of freezing canine skin on the penetration kinetics of hydrocortisone. Skin samples from three dogs were used for in vitro penetration studies commencing on the day of skin collection (fresh skin) and again after freezing at ,20 °C for 1, 4, 8 and 12 months. When the data from the dogs was averaged, the pseudo-steady-state flux (Jss) of hydrocortisone through skin frozen for any duration was significantly (P < 0.023) greater than through fresh skin and there was a positive relationship (P < 0.007) between the length of freezing and ,Jss. For all dogs, the lag times (tlag) calculated for hydrocortisone penetration were significantly (P < 0.029) shorter through skin that had been frozen, compared with fresh skin. However, the shapes of the permeation profiles of hydrocortisone appeared similar through the fresh and frozen dog skins and no differences were detected between the groups on histological examination. The results of this study have shown that freezing dog skin at ,20 °C can significantly increase the transdermal penetration of hydrocortisone in vitro, and that the extent of this enhancement can increase with duration of freezing. [source] Gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal delivery of interleukin-4 using ultradeformable cationic liposomeTHE JOURNAL OF GENE MEDICINE, Issue 6 2010Jiong Li Abstract Background Topical transdermal gene delivery to the skin shows great potential for painless, non-invasive administration of vaccines and therapeutic agents. Interleukin (IL)-4 strategies have shown a good antipsoriatic effect in clinic trials. To date, no information has been acquired on the effectiveness of gene therapy for psoriasis in the K14-VEGF transgenic mouse model by topical transdermal penetration of murine IL-4 (mIL-4) using ultradeformable cationic liposome (UCL). Methods In the present study, we synthesized an UCL and determined a suitable formula for transdermally delivering plasmid DNA to mouse skin. We then tested the antipsoriatic efficacy in the K14-VEGF transgenic mouse model by transdermal delivery of mIL-4 using UCL. Results We found that plasmid DNA was transdermally delivered to vicinal sites of epidermis and hair follicles using this optimized formula. Plasmid DNA expression was detected in ear skin. Twenty-four hours after topical application, plasmid DNA was not detected in blood serum and liver, which may decrease the risk of insertion of promoter from plasmid to genomic DNA. Mice treated with UCL/mIL-4 displayed a mild psoriasis phenotype. Histological analysis of pathological score using the Baker scoring system revealed an antipsoriatic effect. Immunohistochemical analysis revealed that hyperplastic and inflamed vessels were suppressed. Conclusions These observations provide evidence of antipsoriatic efficacy by topical transdermal delivery of mIL-4. Therefore, topical transdermal gene transfer is attractive and offers future potential for application in human patients with other dermatogic diseases. Copyright © 2010 John Wiley & Sons, Ltd. [source] | ||||||||||