挥发油含氧单萜成分的透皮吸收促进作用与皮肤细胞毒性比较研究

目的比较中药挥发油含氧单萜成分的透皮吸收促进作用与皮肤细胞毒性。方法以中药挥发油中常见的9种含氧单萜(1,8-桉叶素、4-萜品醇、樟脑、薄荷脑、α-松油醇、香芹酮、芳樟醇、香叶醇和柠檬醛)为研究对象,比较其对布洛芬的透皮吸收促进效果和对人角质形成细胞HaCaT的细胞毒性。结果 9种含氧单萜成分均能显著促进布洛芬的透皮吸收,且皮肤细胞毒性远低于经典的化学合成促渗剂氮酮,其中1,8-桉叶素的效果最好。环状含氧单萜(1,8-桉叶素、4-萜品醇、樟脑、薄荷脑、α-松油醇、香芹酮)的透皮吸收促进效果优于链状含氧单萜(芳樟醇、香叶醇、柠檬醛),皮肤细胞毒性没有显著差异。结论环状含氧单萜更适合作为透皮吸收促进剂进行开发。     

不同吸收促进剂及酶抑制剂对胰岛素体内及体外口腔黏膜渗透性的影响

目的：研究不同的吸收促进剂及酶抑制剂对胰岛素透过口腔黏膜的影响。方法：体外实验中,在不同吸收促进剂及酶抑制剂作用下,测定胰岛素透过仓鼠和家兔口腔黏膜的渗透系数;体内实验中,在胰岛素口腔喷雾剂中加入不同的吸收促进剂及酶抑制剂,考察大鼠经口腔喷入胰岛素后的血糖降低情况。结果：SDCh, Brij78, SLS以及lecithin可以显著增加胰岛素透过口腔黏膜的渗透系数,而aprotinin,bacitracin, 1-menth ol 以及 poloxamer的作用相对较小。胰岛素溶液中加入SDCh, Brij78, SLS以及lecithin 后,正常大鼠口腔喷雾给药,药理生物利用度都有显著的提高,而aprotinin ,b acitracin, 1-menthol 以及 poloxamer对血糖的影响较小。结论：对于考察吸收促进剂及酶抑制剂对胰岛素的促进吸收作用来说,体外实验与体内实验结果是一致的,可以通过体外实验来粗略地筛选吸收促进剂及酶抑制剂,为体内实验结果提供更多的线索和思路。     

Oncogenic extrachromosomal DNA functions as mobile enhancers to globally amplify chromosomal transcription

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盐酸丁卡因凝胶剂经皮渗透作用

目的：制备盐酸丁卡因凝胶剂，并考察不同透皮促进剂对其透皮吸收的影响。方法：配制含不同透皮促进剂的盐酸丁卡因凝胶剂，采用简单扩散小室和紫外分光光度法测定药物透皮吸收量。结果：加1%月桂氮Zhuo酮，加1%，3%，5%薄荷脑或加两者混合透皮促进剂，将药物碱化均可显著增加盐酸丁卡因凝胶剂的透皮吸收量，其累积释药量与时间呈线性关系。结论：单独使用1%月桂氮Zhuo酮对盐酸丁卡因凝胶透皮吸收作用不明显，3%，5%薄荷脑或加1%月桂氮Zhuo酮两者混合透皮保进剂对盐酸丁卡因凝胶透皮吸收作用明显，1%月桂氮Zhuo酮 3%薄荷脑对盐酸丁卡因凝胶透皮吸收作用最明显。     

Disposition and Metabolic Profiling of the Penetration Enhancer Azone. I. In Vivo Studies: Urinary Profiles of Hamster,Rat, Monkey,and Man

Chain-labeled ¹⁴C-Azone was intravenously administered to hamster, monkey, and rat, to compare its metabolic profile with that obtained previously in humans after dermal application. Azone-derived radioactivity was excreted predominantly in the urine for both hamster and monkey, which is similar to the disposition in humans. Metabolic profiling in urine revealed extensive systemic metabolism to occur in all species studied. The main fraction of the metabolites was most polar in man, followed by rat, monkey, and hamster. Traces of the parent compound were detectable only in hamster urine. Although some of the polar major human metabolites were also present in rat urine, the animals were unsuitable for collecting metabolites of Azone observed in humans. In rats, complete cleavage of the dodecyl side chain was ruled out by administering Azone that had been labeled at two distinct positions of the molecule. Additionally, oral administration of Azone to rats resulted in the same metabolic profile as intravenous administration, indicating that gastrointestinal metabolism does not occur or is similar to systemic metabolism.     

Effect of Absorption Enhancers on Ciliated Epithelium: A Novel In Vivo Toxicity Screening Method Using Rotifers

Pharmaceutical Research -     

TARGETED DRUG DELIVERY TO THE SKIN AND DEEPER TISSUES: ROLE OF PHYSIOLOGY, SOLUTE STRUCTURE AND DISEASE

1. Drug delivery through the skin has been used to target the epidermis, dermis and deeper tissues and for systemic delivery. The major barrier for the transport of drugs through the skin is the stratum corneum, with most transport occurring through the intercellular region. The polarity of the intercellular region appears to be similar to butanol, with the diffusion of solutes being hindered by saturable hydrogen bonding to the polar head groups of the ceramides, fatty acids and other intercellular lipids. Accordingly, the permeability of the more lipophilic solutes is greatest from aqueous solutions, whereas polar solute permeability is favoured by hydrocarbon-based vehicles. 2. The skin is capable of metabolizing many substances and, through its microvasculature, limits the transport of most substances into regions below th. dermis. 3. Although the flux of solutes through the skin should be identical for different vehicles when the solute exists as a saturated solution, the fluxes vary in accordance with the skin penetration enhancement properties of the vehicle. It is therefore desirable that the regulatory standards required for the bio-equivalence of topical products include skin studies. 4. Deep tissue penetration can be related to solute protein binding, solute molecular size and dermal bloo. flow. 5. Iontophoresis is a promising area of skin drug delivery, especially for ionized solutes and when a rapid effect i. required. 6. In general, psoriasis and other skin diseases facilitate drug delivery through th. skin. 7. It is concluded that the variability in skin permeability remains an obstacle in optimizing drug delivery by thi. route.     

Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part I

Preclinical efforts to detect and characterize potential cognition enhancers appear to have been dominated by a strategy of demonstrating a wide variety of apparently beneficial behavioral effects with little attention given to the specific psychological mechanisms underlying behavioral enhancement. In particular, the question of whether or not behavioral facilitation is based on relevant mnemonic mechanisms and is independent of the stimulus properties and/or the motivational and attentional components of a task is not often considered. As a result, an overwhelming number of compounds have failed to produce the clinical effects predicted for them on the basis of preclinical research. The available data suggest that a more successful approach requires deductive research strategies rather than the indiscriminate accumulation of apparently beneficial effects in a variety of behavioral tasks and animal models. The first step towards such an approach is a systematic and rigorous evaluation of the different aspects of validity for the models most frequently used in preclinical research. It is concluded that a combination of good construct validity and good face validity represents a necessary condition for screening tests with predictive validity, and that the most popular paradigms fail to fulfil these criteria. Future screening programs for cognition enhancers will probably be characterized by a depreciation of fast and dirty tests in favor of approaches focussing on the validity of the effects of potential cognition enhancers.     

Ex vivo buccal drug delivery of ropinirole hydrochloride in the presence of permeation enhancers: the effect of charge

In the current study, the ex vivo permeation of ropinirole hydrochloride (RH) across porcine buccal mucosa in the presence of three permeation enhancers, namely N-trimethyl chitosan (TMC) (positively charged) a chitosan derivative, sulfobutyl ether-β-cyclodextrin (SBE-β-CD) (negatively charged) and hydroxypropyl-β-cyclodextrin (HP-β-CD) (neutral), was investigated. Buccal permeation studies were conducted using Franz diffusion cells. Cumulative amounts of RH were plotted versus time. The presence of the permeation enhancers significantly increased the transport of the drug across the porcine buccal epithelium compared to its plain congener (RH solution). The rank order effect of the permeation enhancers for the transport of RH across buccal epithelium was TMC?≥?SBE-β-CD?>?HP-β-CD?>?RH solution. The presence of TMC increased 1.34-fold the transport of RH across buccal epithelium, whereas an increase of 1.23- and 1.28-fold was reported in the presence of HP-β-CD and SBE-β-CD, respectively. Infrared spectroscopy (IR) was employed to investigate the interaction of permeation enhancers with the epithelial lipids of porcine buccal mucosa corroborating the permeation results. Finally, light microscopy was performed to assess the histological changes in the porcine epithelium. Formation of vacuoles, spongiosis and acantholysis linear detachment and destruction of the epithelium resulted from the presence of the permeation enhancers. The data suggest that all enhancers tested, and particularly TMC, increase the transport of RH across buccal epithelium.