Evaluating the Effects of Crystallinity on Drug Release Behaviour in Itraconazole- or Miconazole-Loaded PLGA Microparticles Prepared Using a Co-Grinding Method

This study aimed to prepare and characterize itraconazole (ITCZ)- or miconazole (MCZ)-loaded poly (lactide-co-glycolide) (PLGA) microparticles (MP) using a co-grinding method with ball milling, which is a solvent-free and convenient procedure. PLGA MP was prepared by grinding for 60 min, and the fixed theoretical drug loading was set at 9.1% and 16.7% for both drugs. The obtained loading efficiency for both drugs was estimated to be approximately 100%. The average diameters of the drug-loaded PLGA MP were approximately 20 - 35 μm. Powder X-ray diffraction (PXRD) or differential scanning calorimetry (DSC) confirmed amorphization of ITCZ and MCZ in ITCZ- or MCZ-loaded PLGA MP in all formulations. The drug release percentage from 9.1%-loaded ITCZ-PLGA7505 MP at 24 h was almost 50%, which was higher than that of ITCZ powder. The drug release percentage from MCZ-loaded PLGA7505 MP at 4 h was over 80%, which was higher than that of MCZ powder. This enhancement of release rate is caused by the amorphization of ITCZ or MCZ in the PLGA matrix. MCZ-loaded PLGA7510 MP showed a sustained release profile up to 24 h, suggesting that MCZ exists in an amorphous form in the PLGA matrix;however, the release rate declined owing to the large molecular weight of PLGA. Therefore, the release enhancement of antifungal drugs loaded on PLGA MP could be achieved by their amorphization using a co-grinding method with ball milling.

电压依赖性钾通道与Miconazole在低氧性肺血管收缩中的作用

目的观察大鼠肺动脉平滑肌细胞(PaSMCs)膜上电压依赖性钾通道(Kv)与细胞色素P450氧化酶抑制剂Miconazole在低氧性肺血管收缩中的作用。方法采用急性酶分离法分离出大鼠肺动脉平滑肌细胞(PaSMCs),利用全细胞膜片钳技术记录PaSMCs的Kv通道的电流特性;用低氧液体灌流PaSMCs造成急性低氧模型,记录低氧作用前后Kv通道的电流变化;用不同浓度的Miconazole作用于PaSMCs,记录加药前后的电流变化。结果低氧液体灌流以及不同浓度的Miconazole对Kv均有明显的抑制作用,且Miconazole的抑制作用具有一定的浓度依赖性,在加用Kv的特异性的阻断剂4氨基吡啶(4AP)后再加用该药不能进一步抑制Kv电流。结论低氧和Miconazole均作用于Kv通道的同一部位,支持PaSMCs膜上的Kv通道在低氧性肺血管收缩中起重要作用,而细胞色素P450氧化酶可调节细胞内的氧化还原状态,可能系一重要的氧感受器。

Miconazole对破骨细胞在羟基磷灰石涂层吸收的影响

目的:研究钙离子通道抑制剂miconazole对破骨细胞对羟基磷灰石涂层的吸收的影响。方法:在羟基磷灰石涂层表面诱导破骨细胞,破骨细胞形成后,分别加入不同浓度的miconazole细胞培养基,培养48h后,扫描电镜观察羟基磷灰石表层的吸收陷窝。结果:miconazole可抑制破骨细胞的羟基磷灰石涂层的吸收陷窝面积,且吸收陷窝面积随着miconazole浓度的增加而增加。结论:miconazole可抑制破骨细胞对羟基磷灰石涂层的吸收。

Development of Film Dosage Forms Containing Miconazole for the Treatment of Oral Candidiasis

Film dosage forms (FDs) containing miconazole (MCZ) for the treatment of oral candidiasis were prepared using water-soluble polysaccharides, and the dissolution profiles of MCZ from the FDs were investigated. In addition, the forms were modified by the addition of a surface active agent to accelerate the drug dissolution rate. Circular films incorporating MCZ were obtained using each polysaccharide. Most FDs were easy to handle and resistant to tearing. No diffraction peaks were observed in the X-ray diffractograms of FDs. FDs prepared with sodium alginate or pullulan immediately swelled and disintegrated in aqueous medium, whereas MCZ incorporated in the FD gradually dissolved. A marked acceleration in the MCZ dissolution rate was observed when FD was prepared with polysaccharide containing a surfactant. These results confirmed that modified FDs are useful for treating localized conditions in the oral cavity, such as oral candidiasis, and that FDs can simplify the administration of drugs to patients.

Combination Effect of Miconazole with Polygodial against <i>Candida albicans</i>

The combination effect of miconazole with polygodial against Candida albicans was investigated by an in vitro checkerboard method. Isobolograms, fractional inhibitory concentration (FIC), and fractional fungicidal concentration (FFC) indices were used for evaluating the interaction between compounds combined. The combination of miconazole with polygodial exhibited strong synergism on both fungistatic and fungicidal action against this opportunistic pathogen.

Utility of Miconazole Therapy for <i>Trichosporon</i>Fungemia in Patients with Acute Leukemia

Invasive trichosporonosis is an extremely rare mycosis, but Trichosporon fungemia (TF) in patients with hematologic malignancies has been increasingly recognized to be a fulminant and highly lethal infection. Although the utility of azole therapy has been demonstrated in several observations, little is known about the efficacy of one of azoles, miconazole (MCZ). To assess its therapeutic role, we retrospectively investigated 6 cases of TF in patients with acute leukemia receiving MCZ containing regimens. Successful outcome was obtained in 4 patients [MCZ + amphotericin B (AmB) in 2, MCZ only and MCZ + fluconazole (FLCZ) + AmB in one each], but not in 2 (MCZ + FLCZ + AmB and MCZ + FLCZ in one each). Although MCZ and AmB exhibited good in vitro activities against isolates from all patients, FLCZ had such finding from only one patient. Considering the reportedly limited utility of AmB, MCZ seemed to play a critical role even in the combination therapies for TF. Despite the release of newer azoles and other classes of antifungals, the use of MCZ remains a potential therapeutic approach for TF in patients with acute leukemia.

Effects of Ca^(2+) channel blockers on store-operated Ca^(2+) channel currents of Kupffer cells after hepatic ischemia/reperfusion injury in rats

AIM： To study the effects of hepatic ischemia/ reperfusion （I/R） injury on store-operated calcium channel （SOC） currents （Isoc） in freshly isolated rat Kupffer cells, and the effects of Ca^2＋ channel blockers, 2-aminoethoxydiphenyl borate （2-APB）, SK＆F96365, econazole and miconazole, on Isoc in isolated rat Kupffer cells after hepatic I/R injury.METHODS： The model of rat hepatic I/R injury was established. Whole-cell patch-clamp techniques were performed to investigate the effects of 2-APB, SK＆F96365, econazole and miconazole on Isoc in isolated rat Kupffer cells after hepatic I/R injury.RESULTS： I/R injury significantly increased Isoc from -80.4±25.2pA to -159.5±34.5pA （^bp 〈 0.01, n = 30）. 2-APB （20, 40, 60, 80, 100 pmol/L）, SK＆F96365 （5, 10, 20, 40, 50 pmol/L）, econazole （0.1, 0.3, 1, 3, 10 μmol/L） and miconazole （0.1, 0.3, 1, 3, 10 μmol/L） inhibited Isoc in a concentration-dependent manner with IC50 of 37.41 μmol/L （n = 8）, 5.89 μmol/L （n = 11）, 0.21 μmol/L （n = 13）, and 0.28 μmol/L （n = 10）. The peak value of Isoc in the I-V relationship was decreased by the blockers in different concentrations, but the reverse potential of Isoc was not transformed. CONCLUSION： SOC is the main channel for the influx of Ca^2＋ during hepatic I/R injuries. Calcium channel blockers, 2-APB, SK＆F96365, econazole and miconazole,have obviously protective effects on I/R injury, probably by inhibiting Isoc in Kupffer cells and preventing the activation of Kupffer cells.

Drug interaction presenting as acute abdomen

Warfarin is the most common oral anticoagulant prescribed around the world. Adverse drug interactions with warfarin are a huge problem especially in the elderly and in patients who take multiple medications. Most adverse drug interactions involve concomitantly prescribed oral or intravenous medications. Occasionally, topical or mucosally absorbed drugs can interact, leading to fluctuations in warfarin levels with adverse consequences. In this case report, we describe a case of intestinal intramural hematoma, a rare but known consequence of a supra therapeutic international normalized ratio (INR). The supra therapeutic INR was a consequence of mucosally absorbed miconazole, prescribed for vaginal candidiasis. We wish to highlight this rare and potentially fatal drug interaction, along with the need for frequent INR monitoring when new drugs are added or removed in patients taking warfarin.

Cyclodextrin-Modified Film Dosage Forms for Oral Candidiasis Treatment

Oral candidiasis is a common disease in patients with dry mouth. In this study, film dosage forms (FD) incorporating miconazole nitrate, an antifungal agent, were prepared with water-soluble polysaccharide and cyclodextrin (CD). The dissolution profiles of the drug from the FDs were investigated in limited dissolution medium. Soft films were obtained from sodium alginate containing 0.5% α-CD, β-CD, or γ-CD. Most FDs were easy to handle, though the film tearing resistance was lower than that of CD-free FDs. Addition of CD to the FD accelerated the drug dissolution rate. Interestingly, this phenomenon was also observed in FDs prepared with pullulan. In contrast, acceleration of the drug dissolution rate was not observed when CD polymer was added to the base solution. The initial drug dissolution rate was controllable by the amount of CD added to the FD. Therefore, FDs prepared with these materials are useful to treat oral candidiasis in patients with dry mouth syndrome.

Patient Preferences in the Treatment of Vaginal Candidiasis

Vulvovaginal candidiasis (VVC) is one of the most frequent problems facing women and their healthcare professionals (HCP). It is difficult for providers to understand the prevalence of VVC because effective over the counter treatments (OTC), are available. It is expected that there are a great many more episodes of VVC in our patient population, as the frequency of self-treatment, success and satisfaction for those that use OTC products prior to seeing a women’s health care provider is unknown. In this study;healthcare providers were given OTC miconazole/tioconazole units for free distribution to patients for whom they diagnosed VVC by exam in their offices. Surveys for both HCP and patients were also distributed to determine the initial or recurrent nature of their symptoms and their satisfaction with their treatments. 1265 OBGYNs and 1821 NP/CNM/PAs reported on over 19,000 patients receiving a single complete treatment. Among HCPs, treatment efficacy was the primary reason for recommending miconazole/tioconazole. However, rapid onset of symptom relief, safety vs. fluconazole, patient preference for the less messy ovule, avoidance with drugs metabolized by the liver, and resistance to, or failure on, fluconazole were additional reasons noted for topical preference. Overall, patient satisfaction (n = 317) was high at 95%, with 97% of patients reporting that they would use miconazole again. Importantly, 100% of first time sufferers (n = 95) would use miconazole again. The few patients dissatisfied with miconazole (2%), reported no symptom relief, burning after use, an “allergic reaction”, pain from the applicator or a messy discharge. Most patients using the external symptom relief products were satisfied with the external cream (93%) and wipes (96%). Almost all patients reported their yeast infection was cured (91%) and that they experienced quick symptom relief (94%), despite the prevalence of recurrent vs first time VVA sufferers that presented to offices in this trial. Most patients were cured and satisfied with their treatment, therefore supporting the use of topical miconazole/tioconazole as first line therapy for vulvovaginal candidiasis patients presenting to a healthcare office.

Effectiveness of redcore lotion in patients with vulvovaginal candidiasis: a systematic review and Meta-analysis

OBJECTIVE:To summarize and evaluate the effectiveness and safety of Redcore lotion on treating vulvovaginal candidiasis(VVC)using a systematic review and Meta-analysis of randomized controlled trials.METHODS:A systematic literature search was performed in five English and three Chinese electronic databases up to October 2019.Randomized controlled trials in the treatment for VVC were included;only studies which compared the effectiveness and safety of Redcore lotion plus miconazole with miconazole alone were included.Relative risk(RR)and 95%confidence intervals(CI)were used in the Meta-analysis.RESULTS:Seven studies involving 768 patients suffering from VVC were identified;468 of the patients were pregnant women(60.9%).Combination group(Redcore lotion plus miconazole)was more effective in redu CIng symptomatic episodes of VVC than miconazole alone,with respect to cure rate(RR,1.31;95%CI,1.09-1.57;P=0.01),fungal culture negative rate(RR,1.21;95%CI,1.04-1.41;P=0.01),and effective rate(RR,1.18;95%CI,1.05-1.35;P=0.01).Subgroup analyses for pregnant women also showed that the combination group had superior outcomes with respect to VVC cure rate(RR,1.48;95%CI,1.16-1.88,P<0.01),fungal culture negative rate(RR,1.26;95%CI;1.09-1.47;P<0.01),and effective rate(RR,1.25;95%CI,1.10-1.42;P<0.01).Additionally,the observed risk of adverse events was lower in the combination medication group(RR,0.30;95%CI,0.14-0.65;P<0.01).CONCLUSIONS:Though overall quality of individual studies was low,Redcore lotion plus miconazole can significantly improve clinical effectiveness and safety compared with miconazole alone.