粉防已碱纳米醇质体的制备、表征和抗关节炎疗效(英文)

本研究旨在探索醇质体用于改善粉防己碱局部给药治疗关节炎的可行性。用pH梯度法制备醇质体, 并对其粒径、形态和包封率进行表征。所制备的粉防己碱醇质体为球形, 平均粒径约为78 nm, 包封率为 (52.87±3.81)%。而粉防己碱脂质体具有较大的粒径 (99 nm) 和较高的包封率 (98.80±0.01)%。此外, 与粉防己碱脂质体相比, 粉防己碱醇质体显示出显著的体外透皮性能和抗大鼠关节炎疗效, 并与市售地塞米松软膏的疗效无显著性差异。结果表明, 醇质体有望成为粉防己碱皮肤局部给药的纳米载体。     

Nanosized ethanolic vesicles loaded with econazole nitrate for the treatment of deep fungal infections through topical gel formulation

This project aimed at developing nanovesicles of econazole nitrate (EN) and formulating them as a suitable dermatological gel for improved therapeutic efficacy, better dispersity, and good storage stability. Ethosomes were prepared by cold method and evaluated for the mean diameter, surface charge, and entrapment efficiency. Optimized ethosomes with vesicle size and entrapment efficiency of 202.85 ± 5.10 nm and 81.05 ± 0.13%, respectively, were formulated as Carbopol 934 NF gels with varied permeation enhancers (G1-G7), and compared with liposomal and hydroethanolic gels. The pharmacotechnical evaluation of gels demonstrated G6 with a flux rate of 0.46 ± 0.22 μg/cm(2) hr(1/2) as the best formulation that was able to exhibit controlled release of EN for 12 hours across rat skin, and percent drug diffused from ethosomes was nearly twofold higher than liposomal and hydroethanolic gels. Confocal laser scanning microscopy demonstrated drug permeation as far as the last layer of epidermis (stratum basale). Stability profile of the prepared system assessed for 180 days revealed very low aggregation and insignificant growth in vesicular size. The results collectively suggest that because of the controlled drug release, better antifungal activity, and good storage stability, EN ethosomal gel has tremendous potential to serve as a topical delivery system. FROM THE CLINICAL EDITOR: Ethosomal gel of econazole nitrate was found to have outstanding potential to serve as a topical delivery system, enabling controlled drug release, providing better antifungal activity, and good storage stability.     

Nanosized ethosomes bearing ketoprofen for improved transdermal delivery

The potential of ethosomes for delivering ketoprofen via skin was evaluated. The ethosomes were prepared, optimized and characterized. Vesicular shape, size and entrapment efficiency were determined by transmission electron microscopy, dynamic light scattering and minicolumn centrifugation technique, respectively. Vesicle sizes varied from 120.3±6.1 to 410.2±21.8 nm depending on the concentrations of soya phosphatidyl choline (SPC) and ethanol. Entrapment efficiency increased with concentrations of SPC and ethanol. The formulations exhibited entrapment efficiencies of 42–78%. In vitro release through cellophane membrane showed sustained release of drug from ethosomal formulations in contrast to hydroalcoholic drug solution (HA), which released most of the drug within 2–3 h. In vitro drug permeation across human skin revealed improved drug permeation and higher transdermal flux with ethosomal formulations compared to hydroethanolic drug solution. Kinetics of in vitro skin permeation showed zero order drug release from formulations. Based on in vitro transdermal flux, the estimated steady state in vivo plasma concentration from ethosomes attained therapeutic drug levels whereas hydroalcoholic drug solution exhibited sub therapeutic drug concentration with a patch size of 50 cm². Skin permeation of ethosomal formulations assessed by confocal microscopy revealed enhanced permeation of Rhodamine 123 loaded formulation in comparison to the hydroalcoholic solution.     

乙醇脂质体、二元醇脂质体及传递体对多奈哌齐经皮转运的对比性研究

目的:制备多奈哌齐乙醇脂质体、二元醇脂质体和传递体,并比较皮肤渗透性,从而进一步有效优化药物的经皮转运。方法:通过形态,粒径分布,Zeta电位值和包封率对多奈哌齐乙醇脂质体、二元醇脂质体及传递体进行了初步表征,运用Franz扩散池和共聚焦激光扫描电镜考察了3种囊泡的经皮转运情况。结果:当二元醇脂质体包封率最高(89.1±0.42)%时,乙醇-丙二醇=7∶3,且二元醇脂质体(乙醇-丙二醇为7∶3,W/W)在皮肤中24 h的累积渗透百分数分别是乙醇脂质体和传递体的3.9和5.4倍。结论:二元醇醇脂质体(乙醇-丙二醇为7∶3,W/W)时,有效地改善了药物在醇脂质体中的包封率,且显著增加的药物在皮肤中的累积量。     

Melatonin loaded ethanolic liposomes: physicochemical characterization and enhanced transdermal delivery.

The current investigation aims to evaluate the transdermal potential of novel ethanolic liposomes (ethosomes) bearing Melatonin (MT), an anti-jet lag agent associated with poor skin permeation and long lag time. MT loaded ethosomes were prepared and characterized for vesicular shape and surface morphology, vesicular size, entrapment efficiency, stability, in vitro skin permeation and in vivo skin tolerability. Transmission Electron Microscopy (TEM), Scanning Electron Microscopy (SEM), and Dynamic Light Scattering (DLS) defined ethosomes as spherical, unilamellar structures having low polydispersity (0.032+/-0.011) and nanometric size range (122+/-3.5 nm). % Entrapment efficiency of MT in ethosomal carrier was found to be 70.71+/-1.4. Stability profile of prepared system assessed for 120 days revealed very low aggregation and growth in vesicular size (7.6+/-1.2%). MT loaded ethosomal carriers also provided an enhanced transdermal flux of 59.2+/-1.22 microg/cm2/h and decreased lag time of 0.9 h across human cadaver skin. Fourier Transform-Infrared (FT-IR) data generated to assess the fluidity of skin lipids after application of formulation revealed a greater mobility of skin lipids on application of ethosomes as compared to that of ethanol or plain liposomes. Skin permeation profile of the developed formulation further assessed by confocal laser scanning microscopy (CLSM) revealed an enhanced permeation of Rhodamine Red (RR) loaded formulations to the deeper layers of the skin (240 microm). Further, a better skin tolerability of ethosomal suspension on rabbit skin suggested that ethosomes may offer a suitable approach for transdermal delivery of melatonin.     

Deformable liposomes and ethosomes as carriers for skin delivery of ketotifen

Deformable liposomes and ethosomes were investigated as carriers for skin delivery of ketotifen (KT) in terms of vesicle size, entrapment efficiency, stability, in vitro permeation and skin deposition properties. Phosphatidylcholine (PC) from soybean lecithin was used in the preparation of all vesicles. Sodium cholate, sodium deoxycholate and Tween 80 were investigated as edge activators in preparation of KT deformable liposomes. KT ethosomes were prepared in two PC concentrations, 2% and 4.25% w/v, in 30% v/v ethanol. KT deformable liposomes showed improved entrapment efficiency over KT ethosomes. KT deformable liposomes with Tween 80 as an edge activator were more stable upon storage at 5 +/- 1 degree C than those prepared using sodium cholate or sodium deoxycholate and were more stable than KT ethosomes. In vitro permeation and skin deposition studies employed only deformable liposomes with Tween 80 as an edge activator and ethosomes with 4.25% w/v PC concentration. Both of them improved skin delivery of KT over controls and over traditional liposomes, with greater improvement of KT skin deposition than KT skin permeation, hence are more useful for dermal than for transdermal delivery of KT.     

Synergistic penetration of ethosomes and lipophilic prodrug on the transdermal delivery of acyclovir

The aim of this study was to investigate the lipophilic prodrug as a means of promoting acyclovir (ACV) that exhibited biphasic insolubility into the ethosomes for optimum skin delivery. Acyclovir Palmitate (ACV-C₁₆) was synthesized as the lipophilic prodrug of ACV. The ethosomal system and the liposomal system bearing ACV or ACV-C₁₆ were prepared, respectively. The systems were characterized for shape, zeta potential value, particle size, and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy were used for the percutaneous absorption studies. The results showed that the entrapment efficiency of ACV-C₁₆ ethosomes (87.75%) were much higher than that of ACV ethosomes (39.13%). The quantity of drug in the skin from ACV-C₁₆ ethosomes at the end of the 24 h transdermal experiment (622.89 μg/cm²) was 5.30 and 3.43 times higher than that from ACV-C₁₆ hydroalcoholic solution and ACV ethosomes, respectively. This study indicated that the binary combination of the lipophilic prodrug ACV-C₁₆ and the ethosomes synergistically enhanced ACV absorption into the skin.     

Ethosomes,binary ethosomes and transfersomes of terbinafine hydrochloride: A comparative study

The aim of this study was to compare the skin permeation of ethosomes, binary ethosomes and transfersomes of Terbinafine Hydrochloride (TH) under non-occlusive conditions. These lipid vesicles were prepared and characterized for shape, size, zeta-potential and entrapment efficiency. Franz diffusion cells and confocal laser scanning microscopy (CLSM) were used for the percutaneous absorption studies. The quantity of drug in the skin from ethosomes, binary ethosomes (the weight ratio of ethanol to propylene glycol 7:3, ethanol-PG = 7:3, w/w), and transfersomes was 1.26, 1.51 (p <0.05), 1.56 (p <0.01) times higher than that of TH from traditional liposomes (control). The skin deposition of the applied dose (DD%) of TH from ethosomes, binary ethosomes, and transfersomes was 3.34 (p < 0.05), 9.88 (p < 0.01), 2.52 times higher than that of TH from control. The results of CLSM experiments showed that penetration depth and fluorescence intensity of Rhodamine B from binary ethosomes was much greater than that from ethosomes and transfersomes. These results indicated the binary ethosomes (ethanol-PG = 7:3, w/w) most effectively permitted drug penetration through skin; transfersomes made drug easiest to accumulate in the skin. Ethosomes improved drug delivery with greater improvement in skin permeation than improvement in skin deposition.     

姜黄素醇质体的制备及其质量评价

目的:制备姜黄素醇质体,并考察其理化性质.方法:采用乙醇注入法制备姜黄素醇质体,以包封率为考察指标,采用正交试验法优选处方,并用透射电镜观察其形态,激光粒度仪测定粒径和Zeta电位,以超速离心法分离含药醇质体与游离药物,用HPLC法测定姜黄素醇质体的包封率.结果:优选处方为:姜黄素10 mg、蛋黄卵磷脂350 mg、胆固醇50 mg、乙醇百分浓度25%.实验所制醇质体纳米粒子为类球形囊泡结构,粒径为(210.8±2.0)nm,Zeta电位为(-3.49±0.27)mV,粒径分布均匀,多分散指数(PDI)为(0.144±0.006),以优选后处方制备醇质体,其包封率为(85.55±2.12)%.结论:乙醇注入法适用于姜黄素醇质体的制备,所制醇质体纳米粒子各项物理指标稳定,可用于经皮渗透给药的研究.     

酮洛芬二元醇质体凝胶的研制及其质量考察

目的:研制酮洛芬二元醇质体凝胶,并对其质量进行考察.方法:采用乙醇注入法制备酮洛芬二元醇质体,采用研和法制备醇质体凝胶;透析法测定包封率;Franz扩散池进行离体皮肤渗透试验,测定其体外累积渗透量及皮内滞留量;并对其体外稳定性进行了初步考察.结果:酮洛芬二元醇质体形态圆整,平均粒径为(289.86±44.75)nm,平均包封率为(73.85±2.62)%.体外透过皮肤进入接收液中的二元醇质体(乙醇/丙二醇=7:3)累积渗透量为一元醇质体的1.8倍,24 h时二元醇脂质体和醇质体皮肤中药物滞留量分别为(52.33±3.12)μg·cm-2和(40.25±2.85)μg·cm-2.在实验期内,体外稳定性较好.结论:酮洛芬二元醇质体具更好的透皮吸收性及皮肤滞留性,且质量稳定.     

2种方法制备银杏内酯长循环固体脂质纳米粒的比较

目的:研究银杏内酯AB长循环固体脂质纳米粒(GAB-LSLN)的制备方法,并探讨GAB-LSLN的主要理化性质。方法:分别采用超声法和高压乳匀法制备GAB-LSLN。在电镜下观察其形态,测定其粒径、Zeta电位和包封率,并在室温下放置4周,观察GAB-LSLN的稳定性。结果:超声法制备的GAB-LSLN在透射电镜下呈片状存在,形态不规则;高压乳匀法制备的GAB-LSLN呈球状,形态规则。超声法和高压乳匀法制备的GAB-LSLN粒径分别为(219.6±14.3)nm和(173.9±10.4)nm(P<0.001);Zeta电位分别为(—21.12±1.03)mv和(—27.43±2.14)mV(P<0.001),包封率分别为(85.05±0.67)%和(92.49±0.88)%(P<0.001)。高压乳匀法制备的GAB-LSLN室温放置4周后,粒径无显著增加(P>0.05)。结论:高压乳匀法制备GAB-LSLN具有粒径小、稳定性和包封率高的特点,优于超声法。     

Formulation Development and in vitro Characterization of Proliposomes for Topical Delivery of Aceclofenac

Non-steroidal antiinflammatory drugs are routinely prescribed for the patients with rheumatic disease and such patients are at increased risk of serious gastrointestinal complications, when non-steroidal antiinflammatory drugs administered by oral route. The aim of the present study was to develop and characterized a vesicular drug carrier system (proliposome) for topical delivery of aceclofenac to overcome the problems related with oral route. Aceclofenac proliposome were prepared by the film-deposition on carriers method and characterized for size and surface morphology, drug content in both proliposomes and liposomal system, percent yield, in vitro drug release studies and drug permeation studies. The prepared system was also characterized for drug-excipients interaction by Fourier transform infrared spectrophotometer and stability studies. The size and surface morphology were studied using optical microscopy, scanning electron microscopy and transmission electron microscopy. A spherical shape of reconstituted aceclofenac liposome with an average vesicular size of about 500 nm was observed in photomicrographs. The maximum entrapment efficiency of reconstituted liposomes was 80.31% whereas the drug content in proliposomes was found to be more than 90%. In vitro release of drug was significantly retarded indicating sustained release of aceclofenac from proliposomes. Stability study was performed at various temperatures indicating that aceclofenac proliposomes are stable at lower temperature.     

乙醇脂质体对多奈哌齐经皮转运的促进作用

目的：制备多奈哌齐乙醇脂质体,从而进一步有效优化药物的经皮转运。方法：采用注入法制备多奈哌齐乙醇脂质体;通过形态,粒径分布和包封率对乙醇脂质体进行了初步表征,运用Franz 扩散池和共聚焦激光扫描电镜考察了乙醇脂质体的经皮转运情况。结果：多奈哌齐乙醇脂质体（乙醇含量45%）包封率明显高于多奈哌齐脂质体;多奈哌齐乙醇脂质体透皮量分别为脂质体及乙醇溶液的4.32倍和1.89倍。结论：乙醇脂质体可有效携带药物进入皮肤深层。     

倍他司汀醇质体的制备与评价

目的:研究倍他司汀醇质体最佳处方工艺,并考察其体外透皮特性.方法:采用乙醇注入法制备倍他司汀醇质体,以大豆卵磷脂用量、乙醇用量和水浴温度作为考察因素,粒径、包封率为测定指标,采用星点设计-效应面法优化处方,并考察该制剂的初步稳定性;应用Franz扩散池进行体外透皮吸收试验,比较不同给药形式对倍他司汀经皮渗透的影响.结果...     

5-氟尿嘧啶乙醇脂质体的改性及其透皮吸收研究

目的:研究胆固醇对5-氟尿嘧啶(5-FU)乙醇脂质体的改性及其体外透皮扩散的影响。方法:制备不同胆固醇含量的5-FU乙醇脂质体,并考察胆固醇含量对脂质体粒径、Zeta电位、分散指数、包封率、皮内药物滞留量等指标的影响。结果:加入胆固醇后粒径和Zeta电位变化不大,分散指数从0.584降至0.143,5-FU包封率从28.6%增至48.8%,皮内残留5-FU量从40%增至80%以上。结论:胆固醇不会改变乙醇脂质体的粒径大小及Zeta电位,但可提高其分散性和稳定性;加入适量的胆固醇可提高乙醇脂质体中5-FU的包封率及皮内药物滞留量。     

Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization,in vitro evaluation and preclinical assessment

The present investigation aimed for the development and characterization of ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery and effective treatment against vitiligo. The ethosomes were prepared by central composite design (CCD) and characterized for various quality attributes like vesicle shape, size, zeta potential, lamellarity, drug entrapment and drug leaching. The optimized ethosomes were subsequently incorporated int Carbopol® 934 gel and characterized for drug content, rheological behavior, texture profile, in vitro release, ex vivo skin permeation and retention, skin photosensitization and histopathological examination. Ethosomes were found to be spherical and multilamellar in structures having nanometric size range with narrow size distribution, and high encapsulation efficiency. Ethosomal formulations showed significant skin permeation and accumulation in the epidermal and dermal layers. The fluorescence microscopy study using 123 Rhodamine exhibited enhanced permeation of the drug-loaded ethosomes in the deeper layers of skin. Also, the developed formulation showed insignificant phototoxicity and erythema vis-à-vis the conventional cream. The results were cross-validated using histopathological examination of skin segments. In a nutshell, the ethosomes-based hydrogel formulation was found to be a promising drug delivery system demonstrating enhanced percutaneous penetration of methoxsalen with reduced phototoxicity and erythema, thus leading to improved patient compliance for the treatment against vitiligo.     

醋酸泼尼松龙醇质体的制备及其药剂学性质考察

目的:制备醋酸泼尼松龙醇质体并考察其药剂学性质。方法:采用乙醇注入法制备醇质体。以包封率为指标,以处方中药物与大豆磷脂质量比(A)、胆固醇与大豆磷脂质量比(B)、无水乙醇占处方总量的百分比(C)为考察因素进行正交设计优化处方;考察优化后处方所制醇质体的形态、粒径、Zeta电位、包封率、稳定性等,差示量热分析法考察其热力学特性。结果:最佳处方为平均A包1:封20率,B为1(:766、.C793±0%0.2;9以)%此,处贮方藏制30备d的稳醇定质性体较外好形。圆差整示光量滑热,分平析均法粒结径果为(表2明78,.醋5±酸4泼6.7尼)松nm龙,Z以et无a电定位形为状(态-包31封.6于±醇0.0质4)体m中V,。结论:醋酸泼尼松龙醇质体制备工艺简单,优化处方所制制剂药剂学性质符合要求。     

醋氯芬酸醇质体的制备及体外经皮渗透考察

目的:制备醋氯芬酸(ACF)醇质体并考察其对离体大鼠的透皮能力。方法:采用乙醇注入均质法制备醋氯芬酸醇质体,利用正交试验优化处方;对其粒径、包封率、形态及大鼠离体皮肤经皮渗透量进行考察。结果:优选处方为乙醇用量45%,大豆磷脂用量3%,醋氯芬酸用量0.35%。制备的醇质体平均粒径为102 nm,包封率为48%。醋氯芬酸醇质体的24 h经皮渗透量为821.8μg.cm-2是其45%乙醇溶液的6.36倍。结论:醇质体能显著提高醋氯芬酸经皮渗透量,是经皮给药的优良载体。     

盐酸利多卡因多囊脂质体的制备和质量评价

目的:制备具有缓释特性的盐酸利多卡因多囊脂质体,考察其理化性质。方法:以卵磷脂和胆固醇为膜材,采用复乳法制备盐酸利多卡因多囊脂质体,用透射电镜观察其外观形态,用激光粒度分析仪测定粒径,检测包封率和体外释药特性。结果:盐酸利多卡因多囊脂质体的外观形态圆整、规则,粒径分布在300～700nm及1～6μm两区域,包封率为(27.10±0.66)%。多囊脂质体在pH 7.4的磷酸盐缓冲液中,24h的累积释药百分率为(92.7±3.6)%。结论:盐酸利多卡因多囊脂质体具有一定的缓释特性。     

Systemic and mucosal immune response induced by transcutaneous immunization using Hepatitis B surface antigen-loaded modified liposomes

We have evaluated the efficiency of novel modified liposomes (ethosomes) for transcutaneous immunization (TCI) against Hepatitis B. Antigen-loaded ethosomes were prepared and characterized for shape, lamellarity, fluidity, size distribution, and entrapment efficiency. Spectral bio-imaging and flow cytometric studies showed efficient uptake of Hepatitis B surface antigen (HBsAg)-loaded ethosomes by murine dendritic cells (DCs) in vitro, reaching a peak by 180 min. Transcutaneous delivery potential of the antigen-loaded system using human cadaver skin demonstrated a much higher skin permeation of the antigen in comparison to conventional liposomes and soluble antigen preparation. Topically applied HBsAg-loaded ethosomes in experimental mice showed a robust systemic and mucosal humoral immune response compared to intramuscularly administered alum-adsorbed HBsAg suspension, topically applied plain HBsAg solution and hydroethanolic (25%) HBsAg solution. The ability of the antigen-pulsed DCs to stimulate autologous peripheral blood lymphocytes was demonstrated by BrdU assay and a predominantly TH1 type of immune response was observed by multiplex cytometric bead array analysis. HBsAg-loaded ethosomes are able to generate a protective immune response and their ability to traverse and target the immunological milieu of the skin may find a potential application in the development of a transcutaneous vaccine against Hepatitis B virus (HBV).