The state-of-the-art of atmospheric pressure plasma for transdermal drug delivery

Plasma-enhanced transdermal drug delivery(TDD) presents advantages over traditional methods,including painless application, minimal skin damage, and rapid recovery of permeability. To harness its clinical potential, factors related to plasma’s unique properties, such as reactive species and electric fields, must be carefully considered.This review provides a concise summary of conventional TDD methods and subsequently offers a comprehensive examination of the current state-of-the-art in plasma-enhanced TDD. This includes an analysis of the impact of plasma on HaCaT human keratinocyte cells, ex vivo/in vivo studies, and clinical research on plasma-assisted TDD. Moreover, the review explores the effects of plasma on skin physical characteristics such as microhole formation, transepidermal water loss(TEWL), molecular structure of the stratum corneum(SC), and skin resistance. Additionally, it discusses the involvement of various reactive agents in plasma-enhanced TDD, encompassing electric fields,charged particles, UV/VUV radiation, heat, and reactive species. Lastly, the review briefly addresses the temporal behavior of the skin after plasma treatment, safety considerations, and potential risks associated with plasma-enhanced TDD.

Outcomes of long-acting injectable antipsychotics use in pregnancy:A literature review

BACKGROUND Women with a history of serious psychotic disorders are at increased risk of disease relapse during pregnancy.Long-acting injectable(LAI)antipsychotics have been widely used to improve adherence and prevent relapse in patients with various severe psychotic disorders,but there is a lack of high-quality data from previous research on the safety of LAI antipsychotics during pregnancy.AIM To summarize relevant data on maternal,pregnancy,neonatal,and developmental outcomes from published cases of LAI antipsychotic use in pregnancy.METHODS A literature search was performed through November 11,2023,using three online databases:PubMed/MEDLINE,Scopus,and Web of Science.Case reports or case series that reported information about the outcomes of pregnancy in women who used LAI antipsychotics at any point in pregnancy,with available full texts,were included.Descriptive statistics,narrative summation,and tabulation of the extracted data were performed.RESULTS A total of 19 publications satisfied the inclusion criteria:3 case series,15 case reports,and 1 conference abstract.They reported the outcomes of LAI antipsychotic use in 74 women and 77 pregnancies.The use of secondgeneration LAI antipsychotics was reported in the majority(n=47;61.0%)of pregnancies.First-generation LAI antipsychotics were administered during 30 pregnancies(39.0%).Most of the women(approximately 64%)had either satisfactory control of symptoms or no information about relapse,while approximately 12%of them had developed gestational diabetes mellitus.A minority of cases reported adverse outcomes such as stillbirth,spontaneous abortion,preterm birth,low birth weight,congenital anomalies,and neurological manifestations in newborns.However,there were no reports of negative long-term developmental outcomes.CONCLUSION Currently available data seem reassuring,but further well-designed studies are required to properly evaluate the risks and benefits of LAI antipsychotic use during pregnancy.

Ultrasound-mediated transdermal drug delivery of fluorescent nanoparticles and hyaluronic acid into porcine skin in vitro

Transdermal drug delivery （TDD） can effectively bypass the first-pass effect. In this paper, ultrasound-facilitated TDD on fresh porcine skin was studied under various acoustic parameters, including frequency, amplitude, and exposure time. The delivery of yellow-green fluorescent nanoparticles and high molecular weight hyaluronic acid （HA） in the skin samples was observed by laser confocal microscopy and ultraviolet spectrometry, respectively. The results showed that, with the application of ultrasound exposures, the permeability of the skin to these markers （e.g., their penetration depth and concentration） could be raised above its passive diffusion permeability. Moreover, ultrasound-facilitated TDD was also tested with/without the presence of ultrasound contrast agents （UCAs）. When the ultrasound was applied without UCAs, low ultrasound frequency will give a better drug delivery effect than high frequency, but the penetration depth was less likely to exceed 200 p.m. However, with the help of the ultrasound-induced microbubble cavitation effect, both the penetration depth and concentration in the skin were significantly enhanced even more. The best ultrasound-facilitated TDD could be achieved with a drug penetration depth of over 600 p.m, and the penetration concentrations of fluorescent nanoparticles and HA increased up to about 4-5 folds. In order to get better understanding of ultrasound-facilitated TDD, scanning electron microscopy was used to examine the surface morphology of skin samples, which showed that the skin structure changed greatly under the treatment of ultrasound and UCA. The present work suggests that, for TDD applications （e.g., nanoparticle drug carriers, transdermal patches and cosmetics）, protocols and methods presented in this paper are potentially useful.

Control Effect of Slow-release, Long-acting and Multi-functional New Pesticides on Sugarcane Borders and Woolly Aphids

In order to select the long-acting,low toxic,low-risk and multi-functional new pesticides for the control of sugarcane borders and woolly aphids and precise and efficient application technology,the control effect of 10% monosultap · thiamethoxam granular formulation and 1% Bt · clothianidin granular formulation on sugarcane borders and woolly aphids were studied.The results showed that 10% monosultap·thiamethoxam GR and 1% Bt·clothianidin GR had good control effects on sugarcane borders and woolly aphids.They were ideal slow-release,long-acting,low toxic and multi-functional new pesticides used to control sugarcane borders and woolly aphids.They could be used alternately with other pesticides to delay the emergence and development of pest resistance to pesticides.The best dosage of the two pesticides in the field was 45 kg/hm^2.They could be mixed with fertilizer( 1200-1800 kg/hm^2),scattered in sugarcane ditches or at the base of sugarcane plants,and covered with soil or film from January to July.The control effect on dead heart seedlings damaged by borers could be up to above 79.2%,and the control effect on sugarcane woolly aphids could reach more than 98.8%.In comparison with the control group,the actual yield and sugar content of sugarcane increased by above 41 555 kg/hm^2 and 6.5% respectively.The application of slow-release,long-acting,strong systemic and multi-functional new agents with fertilizer around roots is convenient,precise and efficient,labor-saving,time-saving and environmentally friendly,and is worthy of being widely applied in sugarcane areas.

Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect

Delays in infected wound healing are usually a result of bacterial infection and local inflammation,which imposes a significant and often underappreciated burden on patients and society.Current therapies for chronic wound infection generally suffer from limited drug permeability and frequent drug administration,owing to the existence of a wound biofilm that acts as a barrier restricting the entry of various antibacterial drugs.Here,we report the design of a biocompatible probiotic-based microneedle(MN)patch that can rapidly deliver beneficial bacteria to wound tissues with improved delivery efficiency.The probiotic is capable of continuously producing antimicrobial substances by metabolizing introduced glycerol,thereby facilitating infected wound healing through long-acting antibacterial and anti-inflammatory effects.Additionally,the beneficial bacteria can remain highly viable(>80%)inside MNs for as long as 60 days at 4℃.In a mouse model of Staphylococcus aureus-infected wounds,a single administration of the MN patch exhibited superior antimicrobial efficiency and wound healing performance in comparison with the control groups,indicating great potential for accelerating infected wound closure.Further development of live probiotic-based MN patches may enable patients to better manage chronically infected wounds.

基质组成对抗肿瘤药物白藜芦醇可溶性微针成型及其穿透性的影响

目的评估微针基质组成对白藜芦醇可溶性微针(Res-DMNs)成型性及穿透性能的影响,以提高抗肿瘤药物白藜芦醇的经皮递送效率。方法采用多步减压扩散法制备Res-DMNs,以成膜性、平整度、气泡数和含针率为考察指标,对聚乙烯醇(PVA)不同聚合度的单一基质材料(PVA-0488、PVA-0588、PVA-1788)以及PVA与聚乙烯吡咯烷酮(PVP-K30)混合体系进行成型性评价,以确定最佳混合比例,并对制得的可溶性微针的形貌、溶解性能、机械性能、体外穿刺性能和离体皮肤穿刺效率进行全面评价。结果采用PVA-0588与PVP-K30混合基质(2∶1,体积比)制备的Res-DMNs,其含针率可达90%以上,针长约为720μm,针尖距离约800μm;在刺入皮肤后10 min内,微针几乎完全溶解;通过固定皮肤组织测量,Res-DMNs的刺入深度平均为(535.23±87.24)μm,且刺入率达到92.4%。结论可溶性微针的成型性和穿透性能是其临床应用成功的关键,本研究确定了适宜的基质材料组成,为保证Res-DMNs治疗效果提供了基础。

化妆品中两种典型美白剂的经皮渗透规律

采用离体猪腹部皮肤通过Franz扩散池法对不同剂型化妆品(水、精华液、面霜)中烟酰胺和苯乙基间苯二酚进行了经皮渗透研究。采用高效液相色谱串联-质谱法对接收液和皮肤中的美白剂进行定量分析,并计算美白剂的累积渗透率和皮肤滞留率等指标。同时对3种化妆品的美白功效分别进行了人体评价。结果表明:在3种化妆品中,烟酰胺的渗透率都超过60%,苯乙基间苯二酚的渗透率都低于30%,烟酰胺的经皮吸收能力明显优于苯乙基间苯二酚;2种美白剂在面霜中的渗透率最低。另一方面,脂溶性较强的苯乙基间苯二酚,其皮肤滞留率与累积渗透率的比值更高,表明其更倾向滞留在皮肤中。人体评价结果显示3个样品都具有美白功效,表明添加量与功效之间并非是简单的正相关。

消痛贴膏中润湿剂的透皮促透作用研究

目的评价消痛贴膏中润湿剂的透皮促透作用。方法选择消痛贴膏中主药独一味所含木犀草素为模型药物，采用离体扩散池法，以高效液相色谱测定接受液中木犀草素的含量。含量测定采用Platisil C18色谱柱（4．6mm×250mm，5μm，迪马公司）；乙腈：0．1％磷酸（35：65）为流动相；检测波长为350nm；流速1．0ml·min^-1。结果木犀草素进样量在0．04088～2．044μg范围内与峰面积线性关系良好，r=0．9998。与对照组渗透系数0．3732相比，加润湿剂组渗透系数3．97，渗透系数增加10．63倍。结论该润湿剂能增加消痛贴膏中木犀草素的渗透速率和累积透过量。

伊维菌素长效透皮剂的研制及含量测定

为了研制伊维菌素长效透皮吸收剂,依据伊维菌素的理化特性,以高效渗透促进剂氮酮、无水乙醇、N,N-二甲基甲酰胺、丙二醇、α-吡咯烷酮等为赋型剂进行多种溶剂系统组合与筛选,成功研制出含伊维菌素分别为0.5%、1.0%、1.5%的伊维菌素长效透皮剂。稳定性试验结果表明,-20、4、40℃等条件下,以18%无水乙醇、2%氮酮、50%N,N-二甲基甲酰胺、30%α-吡咯烷酮为溶剂制成的伊维菌素长效透皮剂稳定性最好;高效液相色谱法测定结果表明,0.5%、1.0%、1.5%伊维菌素长效透皮剂的日内精密度和日间精密度均小于1%,回收率均在90%左右,3个批次的伊维菌素含量在99.23%~108.02%(1个批次1.5%制剂为122.48%除外),1.0%、1.5%制剂的3次测定和平均含水量均在1%以下。

透皮促进剂对肤康祛斑凝胶体外透皮吸收的影响

目的考察透皮促渗剂对肤康祛斑凝胶的主药熊果苷体外经皮渗透的影响。方法对优化后的肤康祛斑凝胶处方,以大鼠离体皮肤作为渗透屏障,用高效液相色谱法测定凝胶中熊果苷经皮透入接收液含量。考察氮酮、氮酮-薄荷油、氮酮-冰片作为促渗剂对熊果苷透皮吸收的影响。结果肤康祛斑凝胶中熊果苷的体外累积渗透率符合Weibull分布,以氮酮-薄荷油作为促渗剂的处方中,熊果苷累积渗透率最高,渗透促进剂的促透效果为:氮酮-薄荷油>氮酮-冰片>氮酮。结论以氮酮-薄荷油作为促渗剂,对熊果苷有较好的促渗作用。

不同含量伊维菌素长效透皮制剂在家兔体内的药代动力学研究

研究制备伊维菌素含量分别为0.5%、1.0%、1.5%的长效透皮剂,进行3组相同药量不同体积伊维菌素长效透皮剂在家兔体内的药代动力学试验,研究其代谢过程。优化高效液相色谱-荧光检测器测定血浆中伊维菌素含量的方法,通过绘制标准曲线、对精密度、回收率、检测限和定量限的测定,表明该方法符合生物样品的分析要求。对家兔外耳廓单次均匀喷洒给药,通过血浆中伊维菌素质量浓度随时间的数据变化表明,药物可快速经皮肤吸收入血,发挥效应。伊维菌素含量为0.5%、1.0%、1.5%的伊维菌素长效透皮剂依次记为1、2、3组,通过PKSolver药动学处理软件对数据分析发现,1、2、3组吸收半衰期分别为0.52、0.35和0.75 d;达峰时间分别为1.47、1.13和1.23 d;峰质量浓度分别为91.09、37.61和69.53μg·L^-1;消除半衰期分别为3.55、4.95和4.61 d;平均滞留时间依次为9.995、11.902和6.995 d。药时曲线面积分别为7578.33、5530.75和2542.20μg·d·L^-1。3组药物在家兔血浆内均符合有吸收一室开放模型,且第2组吸收半衰期和达峰时间最短,平均滞留时间最长,效果最好。结果表明,本研究制备的伊维菌素长效透皮剂在家兔体内的血药质量浓度变化平稳,释药时间较长,在体内维持有效药物质量浓度时间长达35 d,有明显的长效作用。

伊维菌素长效透皮剂和普通注射剂在家兔体内的药代动力学比较研究

为比较研究制备的伊维菌素长效透皮制剂与普通伊维菌素注射剂药物代谢及药效时间,本研究制备伊维菌素含量分别为0.5%、1.0%和1.5%的长效透皮制剂,采用高效液相色谱法检测不同药量相同体积伊维菌素长效透皮制剂和普通伊维菌素注射剂(1.0%)在家兔体内的药代动力学,并通过PKSolver药代动力学处理软件对数据进行分析。结果显示,0.5%、1.0%、1.5%伊维菌素长效透皮剂和1.0%普通注射剂吸收半衰期分别为0.81、0.52、1.02和0.12 d;达峰时间为1.55、0.97、1.62和0.42 d;峰浓度为47.36、72.02、115.30和99.53 ng/mL;消除半衰期为3.61、5.92、5.59和1.79 d;平均滞留时间为5.27、7.37、5.13和2.16 d;药时曲线面积为1488.70、3081.98、3161.20和480.00 ng·d/mL,伊维菌素长效透皮剂体内维持有效药物浓度的时间长达35 d,普通注射剂仅为9 d。结果表明,伊维菌素长效透皮剂效果稳定,可进行更深入的研究。

苦参碱制剂的研究进展

查阅近年来国内外的相关文献及资料,并进行分析、归纳、总结。目前在临床上广泛使用的制剂主要有苦参碱注射剂、胶囊剂、片剂和栓剂等。对苦参碱缓控释制剂、透皮吸收制剂、靶向制剂、凝胶系统、微球、纳米粒等新剂型的研究也取得了很大进展。加强苦参碱制剂方面的研究,有利于提高其疗效,对于全面开发利用苦参碱具有十分深远的意义。

TTS-ST93-1穴位贴剂防治运动病的观察

目的 :确定合适的防治运动病的经络穴位 ,观察TTS -ST93 -1作为穴位贴剂的抗运动病作用。方法 :有近期晕车史的年青健康自愿者 1 63名 ,男性 ,乘卡车、装甲车 3h。采用随机分组、双盲实验方法。分为实验药物组 (TTS -ST93 -1贴剂膜片 ) ,阳性对照组 (TTS -Scop贴剂膜片 ) ,阴性对照组 (乳糖贴剂膜片 )。选择穴位 :内关、神阙、脉。实验药物组又分 :ST93 -1内关组 ,ST93 -1神阙组 ,ST93 -1脉组。按美国Graybiel制定的运动病症状数字评分法 ,评定被试者的晕车症状程度。结果 :ST93 -1贴剂的平均有效率为 95 9% ,与阴性对照组比较有显著性差异 (P <0 0 1 )。ST93 -1内关组的保护率为 45 5 % ,神阙组的保护率是81 4% ,脉组的保护率为 1 0 0 % ,平均保护率是 76 0 % ,与阳性对照组 (2 7 3 % )比较有显著性差异。ST93 -1贴剂引起的口干、嗜睡、困倦副作用的发生率与阴性对照组比较无显著性差异。被试者穴位上贴药 8h后 ,ST93 -1引起的皮肤红肿、痛、痒等过敏症状较轻。结论 :TTS -ST93 -1有效穴位贴剂是防治运动病的良好方法。

王灵台教授论中药透皮剂肝舒贴的研制思路

介绍王灵台教授研制肝舒贴的思路。王氏认为肝病胁痛多由气虚血瘀所致 ,确定黄芪和夏枯草等中药为主要药物 ,结合经络腧穴、透皮给药理论开发肝舒贴透皮剂。动物实验和临床研究皆证明肝舒贴透皮剂有效。

正交设计金英黄归液透皮剂的制备

为了考查影响金英黄归液透皮剂的因素及透过效果,本试验将基质配方、乳化剂、温度作为可变因素,选用L9(34)正交表进行试验,研究影响金英黄归液透皮剂制备的因素,采用离心试验、耐寒耐热试验、加速试验考查其稳定性,应用透皮扩散池采用紫外分光光度法研究其透过率。结果显示,基质配方、乳化剂、温度对透皮剂分层时间和性能的影响不显著(P>0.05),其影响顺序为基质用量>温度>乳化剂用量,在耐寒耐热、离心和加速试验中未见分层破乳、霉败、色泽和均匀性改变等现象,其稳定性良好;其透过率为15.1μg/cm2.h,这将为生产上制备透过率好稳定的金英黄归液透皮剂提供良好的试验数据。

地肤子总皂苷凝胶剂的制备及体外透皮吸收实验研究

制备地肤子总皂苷凝胶剂并研究其体外透皮吸收特点。采用乙醇回流法提取并采用大孔吸附树脂进行纯化得到地肤子总皂苷;采用离体透皮实验并采用紫外分光光度法测定接受液中总皂苷的含量,计算单位面积累积渗透量,分析药物透皮渗透的特点。结果表明,提取纯化工艺为:地肤子药材用8倍量70%乙醇,回流提取3次,每次2 h,合并提取液,过滤,浓缩至0.80 g/mL(W/V),装柱(D-101),用3倍柱体积水除杂,弃去水洗脱液,用4倍柱体积50%乙醇洗脱,收集洗脱液,回收乙醇;凝胶剂的制备工艺为:将卡波姆充分溶胀,制得空白凝胶,加入地肤子总皂苷溶液,混匀,即得;离体透皮实验研究中,地肤子总皂苷凝胶剂中总皂苷在1.5~9 h的透皮渗透速度基本稳定,但在前1.5 h内有较为明显的时滞现象。该方法制得的地肤子总皂苷凝胶剂,具有良好的成型性和稳定性及释药速度稳定的特点。

跌创散加用透皮剂外敷促进家兔骨折模型愈合的实验研究

目的通过观察跌创散加用透皮剂外敷促进家兔骨折愈合过程中ALP,Ca2+,P3+浓度变化,不同时期X线的变化及骨痂病理组织学改变,研究跌创散加透皮剂对闭合性骨折愈合作用的影响。方法取兔龄为6个月左右的雄性新西兰大耳白兔,造成左胫骨中下段闭合性骨折模型,骨折处连续给予跌创散加用透皮剂外敷,分别于2,4,8周观察兔左胫骨骨折愈合过程中血清ALP,Ca2+,P3+浓度变化,不同时期X射线的变化,骨痂病理组织学改变。结果跌创散加用透皮剂外敷能明显提高血清中ALP浓度及钙磷乘积;提高骨折断端愈合的X评分;增加骨痂中毛细血管和成骨细胞的数量;与模型组比较差异显著。结论跌创散加用透皮剂外敷具有明显促进家兔闭合性骨折愈合的作用,缩短骨折愈合时间。

药物透皮剂及促渗方法研究概况

随着药物制剂研究的不断发展,安全可控的经皮给药方式在临床应用中发挥着越来越重要的作用。经皮给药方式较传统的口服给药和注射给药具有无肝首过效应、血药浓度持久可控、减少给药次数、临床给药方便等优点,有着更广阔的应用空间。论文根据近年来有关经皮给药制剂的相关文献,就经皮给药新载体及促渗技术进行综述,并对目前经皮给药应用存在的问题进行分析,以期为经皮给药制剂的研发提供参考。

中药经皮给药治疗疼痛临床研究

目的观察中药经皮给药治疗疼痛的临床疗效。方法共选择疼痛患者1 621例,其中闭合性胸肋部软组织损伤1 080例,腰背肌筋膜炎181例,肩关节周围炎360例,将每种疾病患者随机分为治疗组和观察组,治疗组用祛风散寒、活血通络、消炎止痛中药的乙醇提取液喷洒患处;对照组给予常规治疗。所有患者治疗前后进行疼痛评分,比较两组疼痛缓解时间和临床疗效。结果对于3种疾病,治疗组疼痛缓解时间和疼痛评分显著低于对照组(P<0.01),总有效率显著高于对照组(P<0.01)。结论具有祛风散寒、活血通络、消炎止痛的中药经皮给药治疗疼痛见效快,疗程短,治愈率高。