Serum levels of sirtuins, leptin and adiponectin in women with pregnancy-induced hypertension.

INTRODUCTION: Pregnancy-induced hypertension (PIH) and preeclampsia (PE) are associated with disturbed maternal inflammatory response, oxidative stress and vascular endothelial cell dysfunction. Obesity is one of risk factors of PE. Leptin is elevated in obesity and its level correlates positively with the amount of adipose tissue. In contrast, adiponectin levels are decreased in obesity. Sirtuins are expressed in the placenta, however their role in pregnancy-related pathology in humans is not known. AIM OF THE STUDY: The aim of our study was to measure serum concentrations of selected sirtuins, adiponectin and leptin in healthy pregnancy and in women with PIH. MATERIALS AND METHODS: The study included 70 women: 38 healthy pregnant women and 32 women with PIH. Blood samples were obtained between the 20th and 40th week of gestation. Serum levels of sirtuins 1, 3, 6, leptin and adiponectin were measured with ELISA. RESULTS: Leptin levels were significantly higher in PIH group as compared to the controls and correlated positively with BMI. Highest leptin levels were observed in women who needed a cesarean section. Levels of sirtuins 1, 3 and 6 were similar in both groups and did not correlate with BMI. CONCLUSIONS: High leptin levels in PIH women during 3rd trimester might be helpful to predict the necessity for a caesarian section. Blood levels of sirtuins 1, 3 and 6 measured after the 20th week of gestation cannot be regarded as a single diagnostic test for PIH or preeclampsia. More studies to clarify significance of sirtuins in PIH and PE development and diagnosis are needed.

Treatment outcomes of patients with primary tracheal tumors - analysis of a large retrospective series.

OBJECTIVE: Primary tracheal tumors are very rare and their management is not definitely established. Due to its rarity, providing patient care in terms of optimal management poses a considerable challenge. The purpose of this study was to investigate treatment outcomes in patients with these rare tumors. METHODS: We carried out a retrospective analysis of 89 patients with primary tracheal tumors treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, over sixteen years. The study assessed patient demographics, tumor characteristics and treatment. Different treatment options were compared in terms of overall survival, disease-free survival, and progression-free survival. RESULTS: A total of 89 patients were included in the study. In the group presented, 45 patients underwent primary radical treatment and 44 were qualified for palliative treatment. Surgical resection was performed in 13 patients out of radically treated patients. The 5 year OS rates in the group of patients who underwent radical treatment and in the group of patients who underwent palliative treatment were 45.9% and 2.3%, respectively. In the group of patients who underwent radical surgical treatment, the 5 year OS was 76.9% compared to 35.8% in the group of patients who underwent nonsurgical treatment. CONCLUSION: A multidisciplinary team should decide treatment options, including in-depth consideration of surgical treatment options.

Does the Freeze-Thaw Technique Affect the Properties of the Alginate/Chitosan Glutamate Gels with Posaconazole as a Model Antifungal Drug?

Hydrogels are semi-solid systems with high flexibility, which, due to holding large amounts of water, are similar to natural tissues and are very useful in the field of biomedical applications. Despite the wide range of polymers available to form hydrogels, novel techniques utilized to obtain hydrogels with adequate properties are still being developed. The aim of this study was to evaluate the impact of the freeze-thaw technique on the properties of cryogels based on sodium alginate and chitosan glutamate with posaconazole as a model antifungal substance. The effect of the freezing and thawing process on the physicochemical, rheological, textural and bioadhesive properties of prepared cryogels was examined. Additionally, the antifungal activity against Candida albicans, Candida parapsilosis and Candida krusei of designed formulations was examined. It was shown that the freeze-thaw technique significantly improved viscosity, bioadhesiveness, textural properties and prolonged the in vitro posaconazole release. Moreover, alginate/chitosan glutamate cryogels exhibited higher values of inhibition zone in C. parapsilosis culture than traditional hydrogel formulations.

The Influence of Tea Tree Oil on Antifungal Activity and Pharmaceutical Characteristics of Pluronic® F-127 Gel Formulations with Ketoconazole.

Fungal skin infections are currently a major clinical problem due to their increased occurrence and drug resistance. The treatment of fungal skin infections is based on monotherapy or polytherapy using the synergy of the therapeutic substances. Tea tree oil (TTO) may be a valuable addition to the traditional antifungal drugs due to its antifungal and anti-inflammatory activity. Ketoconazole (KTZ) is an imidazole antifungal agent commonly used as a treatment for dermatological fungal infections. The use of hydrogels and organogel-based formulations has been increasing for the past few years, due to the easy method of preparation and long-term stability of the product. Therefore, the purpose of this study was to design and characterize different types of Pluronic® F-127 gel formulations containing KTZ and TTO as local delivery systems that can be applied in cases of skin fungal infections. The influence of TTO addition on the textural, rheological, and bioadhesive properties of the designed formulations was examined. Moreover, the in vitro release of KTZ, its permeation through artificial skin, and antifungal activity by the agar diffusion method were performed. It was found that obtained gel formulations were non-Newtonian systems, showing a shear-thinning behaviour and thixotropic properties with adequate textural features such as hardness, compressibility, and adhesiveness. Furthermore, the designed preparations with TTO were characterized by beneficial bioadhesive properties. The presence of TTO improved the penetration and retention of KTZ through the artificial skin membrane and this effect was particularly visible in hydrogel formulation. The developed gels containing TTO can be considered as favourable formulations in terms of drug release and antifungal activity.

Alginate Oligosaccharides Affect Mechanical Properties and Antifungal Activity of Alginate Buccal Films with Posaconazole.

Sodium alginate and its oligosaccharides through potential antifungal properties might improve the activity of antifungal drugs enhancing their efficacy and potentially reducing the frequency of application. Mucoadhesive buccal films are oral dosage forms designed for maintaining both local or systemic drug effects and seem to be a very promising alternative to conventional oral formulations. Hence, in this study, mucoadhesive buccal films based on the alginate and its oligosaccharide oligomer composed predominantly of mannuronic acid for the administration of posaconazole-antifungal drug from the azole group were developed. As the polymer gelation method, a relatively new freeze-thaw technique was chosen. All prepared formulations were examined for pharmaceutical tests, swelling, mechanical, and mucoadhesive properties. In addition, the influence of sodium alginate (ALG) and alginate oligosaccharides (OLG) on POS antifungal activity on Candida species was performed. It was observed that film formulation containing 1% ALG and 1% OLG (F2) was characterized by optimal mucoadhesive and swelling properties and prolonged drug release up to 5 h. Additionally, it was shown that OLG affected the growth reduction of all tested Candida spp. The obtained data has opened the way for future research for developing OLG-based dosage forms, which might increase the activity of antifungal drugs.

Novel Gel Formulations as Topical Carriers for the Essential Oil of Bidens tripartita for the Treatment of Candidiasis.

The genus Bidens L. (Asteraceae) refers to several species of plants used in traditional phytotherapeutic preparations. B. tripartita, also known as bur marigold, is the most familiar plant and has been known as a remedy for chronic dysentery. The hydrodistilled essential oil of the aerial parts of the Polish B. tripartita was analyzed using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) techniques. To exclude any potential toxic effects of the oil on human dermal fibroblasts, the MTT test (methyl thiazolyl tetrazolium) and COMET assay (single-cell gel electrophoresis) were performed. Novel gel formulations as topical carriers for essential oil obtained from B. tripartita were developed and characterized. The bioadhesive properties of the designed preparations in the ex vivo model using the skin of hairless mice were also evaluated. The therapeutic efficacy of the topical formulations is influenced by active phytoconstituents and vehicle characteristics. The antifungal properties of the essential oil of B. tripartita were also tested against Candida species, and this oil appears to be a promising topical anticandidal agent.

Management of symptomatic ascites and post-operative lymphocysts with an easy-to-use, patient-controlled, vascular catheter.

OBJECTIVE: Malignant ascites (MA) can be managed with paracentesis, diuretics, shunt-systems, chemotherapy, and targeted therapies. Some treatments are ineffective; others are associated with complications, involve inpatient procedures, or are not cost-effective. Postoperative lymphocysts (LCs) are managed with inpatient drainage and sclerotherapy or surgery. We tested the use of a vascular catheter in the management of symptomatic MA and LC. METHODS: Fifty-five patients with primary or recurrent cancers with ascites or LCs were managed for symptom relief. A central venous 14-Ga 16-cm catheter (Arrow) was inserted into the abdominal cavity or LC, followed by drainage. RESULTS: The catheter was safely inserted with ultrasound guidance in 43 patients with MA (39 with ovarian cancer: 9 before primary cytoreduction, 30 with recurrence; 4 non-gynecological cancers), and 12 patients with LCs (10 retroperitoneal, 2 bilateral inguinal). All procedures were performed in the outpatient department under local anesthesia, without insertion-related complications. Within a mean of 30 days after catheter placement (range: 7-90 days), no grade 3 infection, peri-drain leakage, or self-removal was noted. In three patients with recurrent ovarian mucinous ascites and one patient with an inguinal LC, some drain obstruction was noted. In cases before primary cytoreduction for ovarian cancer, drainage enabled better nutritional and anesthiological outcomes. Patients with chronic ascites were able to self-monitor the amount of evacuated fluid. Twelve patients whose ascites were drained had chemotherapy at the time, and they reported better well-being, and we estimated better performance status. LC drainage followed by sclerotherapy enabled symptom control and LC radical treatment. CONCLUSION: The use of the vascular catheter is safe, easy, and cost-effective in the management of symptomatic MA and LC.

The Effect of Cationic Polyamidoamine Dendrimers on Physicochemical Characteristics of Hydrogels with Erythromycin.

Polyamidoamine dendrimers (PAMAM) represent a new class of hyperbranched, monodisperse, three-dimensional polymers with unique properties, which make them very promising carriers of antimicrobial agents. The present study aimed to evaluate the influence of PAMAM-NH2 dendrimers generation two (G2) or three (G3) on physicochemical characteristics and structure of hydrogels with a model antibacterial lipophilic drug-erythromycin-commonly used in topical applications. From the obtained rheograms, it can be concluded that tested hydrogels were non-Newtonian thixotropic systems with shear-thinning behaviour. The dissolution tests revealed that erythromycin was definitely faster released from formulations containing PAMAM-NH2 in concentration and generation dependent manner. However, the addition of PAMAM-NH2 to hydrogels evoked only slight improvement of their antibacterial activity. It was also shown that the structure of hydrogels changed in the presence of PAMAM-NH2 becoming less compact, diversified and more porous. Designed hydrogels with PAMAM-NH2 G2 or G3 were stable stored up to three months at 40 ± 2 °C and 75% ± 5% RH.

Analysis of treatment results in primary germ cell tumours with mediastinal location: own experience.

INTRODUCTION: Primary germ cell tumours with mediastinal location comprise 1-6% of mediastinal tumours and 2-5% of all germ cell tumours occurring in adults. They are identified mostly in the 3rd decade of life, in 90% of cases in men. The most common symptoms are dyspnea, chest pain, cough, fever and weight loss. The aim of the present study was the analysis of our own results of treatment of primary germ cell tumours with mediastinal location, and a review of the literature concerning this subject. MATERIAL AND METHODS: Five patients (4 males, 1 female) median age 27.8 years (range 23-30 years) treated in the period from 1999 to 2009 in Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Lung Cancer and Chest Tumours in Warsaw, due to germinal tumours with primary mediastinal location, entered the study. RESULTS: All patients received chemotherapy according to the BEP regimen. All patients achieved an objective response to treatment. Two patients died due to disease progression in spite of II- and III-line treatment. Three patients are still in follow-up. The median survival time was 55.8 months (range 8.0-120.0 months). CONCLUSIONS: Primary mediastinal germ cell tumours have worse prognosis than do those with gonadal location. Based on our observations and review of the literature, it can be concluded that the results of treatment of non-seminoma type germ cell tumours with primary mediastinal location remain poor. Patients who develop early recurrence or progression during first-line chemotherapy are particularly at risk of unfavourable outcome. Identification of new standards of treatment in tumours resistant to cisplatin require further studies evaluating the effectiveness of new generation cytostatic drugs.

Evaluation of the impact of tragacanth/xanthan gum interpolymer complexation with chitosan on pharmaceutical performance of gels with secnidazole as potential periodontal treatment.

Periodontitis consists a group of dental disorders that affect about 70 % of the world population. The therapy mainly relies on mechanical removing bacterial biofilm, nevertheless, local or systemic antibacterial agents play a key role in treating the acute conditions. Secnidazole is a newer derivative of commonly used metronidazole with high safety profile and broad spectrum of antimicrobial activity. The aim of the study was to evaluate the applicability of polyelectrolyte complex-based hydrogels composed of anionic tragacanth with addition of xanthan gum and cationic chitosan as carriers for buccal/intra pocket delivery of secnidazole. Prepared hydrogels with 5 % and 10 % (w/w) drug content were evaluated pharmaceutically towards inter alia physicomechanical, rheological and thermal properties, drug release kinetics, swelling behavior or antimicrobial activity. Cytotoxicity against human primary umbilical vein endothelial cells was also assessed with two independent method. Stable compositions with secnidazole were obtained, however, various miscibility of the drug with the polymers was noted. By adding chitosan, antibacterial activity and swelling performance of the gels were improved, nevertheless, drop of the mucoadhesiveness was also recorded. Hydrogels with 5 % secnidazole were selected as effective antimicrobial compositions with the highest cytocompatibility. They might be considered as promising for oromucosal application with special attention given to SEC as an alternative locally administered antimicrobial agent.

Suspensions of antibiotics in self-emulsifying oils as a novel approach to formulate eye drops with substances which undergo hydrolysis in aqueous environment.

The aim of this study was to develop eye-drops with cefuroxime (CEF) sodium or vancomycin (VAN) hydrochloride, antibiotics that are instable in water. Anhydrous self-emulsifying oils (SEO) are proposed as a carrier and antibiotics are suspended. In the contact with tear fluid, the formulation should transform into emulsion, with fast dissolution of an antibiotic. CEF or VAN (5% w/w) was suspended in SEO carriers prepared by dissolving surfactants (Tween 20 or Span 80 5% w/w) in Miglyol, castor oil, or olive oil. Formulations with or without sodium citrate (2% w/w) were compared. Six-months or 1-year stability tests were carried out at 40 °C. The content of CEF and VAN was evaluated using HPLC and the potency of the antibiotic was assessed with agar diffusion method. In contact with water, drug particles suspended in SEO dissolved rapidly and o/w emulsion was formed. After 1-year at 40 °C, the content of degradation products was at most 0.5% in CEF and 4.0% in VAN formulations. The agar diffusion assay has shown that CEF and VAN loaded into SEO retained its potency against the sensitive microorganisms comparable to an aqueous solution. Therefore, SEO can be used as a novel carrier for the active substances which may not require improved solubility or absorption but need to be protected from moisture. This is a formulation that can be produced on industrial scale, with no limitation of stability or drug concentration.

Lung Cancer in Women-Sociodemographic, Clinical and Psychological Characteristics with Comparison to Men.

(1) Background: There is a difference in the course of lung cancer between women and men. Therefore, there is a need to evaluate various factors in the patient population treated in daily practice. The purpose of this study was to analyze the clinical, sociodemographic and psychological aspects of female lung cancer. To better express the results, we compared women and men. (2) Methods: Consecutive patients with a history of lung cancer treatment admitted to the outpatient oncology clinic (Department of Lung Cancer and Chest Tumours, Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw) and the Department of Internal Medicine, Pulmonary Diseases and Allergy, were enrolled. We conducted analyses of the clinical, psychological and socioeconomic factors of women with lung cancer treated in everyday practice, including a comparison with a group of men. Demographic data were collected from a self-administered questionnaire. We used the Perceived Stress Scale (PSS-10) and Acceptance of Illness Scale (AIS) questionnaires for psychological evaluation. (3) Results: A total of 100 patients with confirmed primary lung cancer with a history of treatment were enrolled in the study (50 women and 50 men). We found a significantly shorter history of smoking in the group of women; at the same time, there were no differences in the reported incidence of COPD. Despite comparable results to men on the psychological questionnaire (PSS-10, AIS), women more often reported a willingness to be supported by a psychologist or psychiatrist due to lung cancer. However, they did not decide to consult them more often than men. Immunotherapy was a significantly less frequently used method in women. (4) Conclusions: We should be more active in finding out the willingness to consult a psychologist or psychiatrist among women with lung cancer. The diagnosis of COPD should be considered more often among women due to the lack of differences in the reported incidence of COPD between men and women, despite a clear contrast in the number of pack-years.

New developments in the imaging of lung cancer.

Radiological and nuclear medicine methods play a fundamental role in the diagnosis and staging of patients with lung cancer. Imaging is essential in the detection, characterisation, staging and follow-up of lung cancer. Due to the increasing evidence, low-dose chest computed tomography (CT) screening for the early detection of lung cancer is being introduced to the clinical routine in several countries. Radiomics and radiogenomics are emerging fields reliant on artificial intelligence to improve diagnosis and personalised risk stratification. Ultrasound- and CT-guided interventions are minimally invasive methods for the diagnosis and treatment of pulmonary malignancies. In this review, we put more emphasis on the new developments in the imaging of lung cancer.

Pulmonary Benign Metastasizing Leiomyoma in a Postmenopausal Woman: A Case Report and Review of the Literature.

Pulmonary benign metastasizing leiomyoma (PBML) is a rare condition characterized by the spread of uterine leiomyomas to the lungs, typically observed in premenopausal women with a history of hysterectomy or myomectomy. This report presents a unique case of a postmenopausal woman, aged 65, that emphasizes the clinical, radiological, histologic, and immunohistochemical aspects of the disease. On presentation, the patient suffered from severe pain. On imaging, a sizable lung tumor was found. Histopathological examination and immunoprofiling confirmed PBML. The patient underwent various treatments, including surgery, radiation therapy, and hormonal therapy, illustrating the challenges in managing PBML. A literature review underscores the rarity of PBML and its diverse clinical manifestations. This study provides valuable insights into the complexities of PBML.

Clinicopathological characteristics of patients with primary tracheal tumors: Analysis of eighty-nine cases.

BACKGROUND: Primary tracheal tumors are very rare and the literature on this subject is limited. The most common histological type of primary tracheal tumors is squamous cell carcinoma (SCC), followed by adenoid cystic carcinoma (ACC). Limited knowledge exists regarding the behavior and outcomes of different histological types of tracheal cancers. The present study aimed to address this gap by assessing the significance of the histological type of primary tracheal tumors based on our own data and to review the literature. METHODS: We carried out a retrospective analysis of 89 patients with primary tracheal tumors treated at the Maria Sklodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between 2000 and 2016. The study assessed patient demographics, tumor characteristics and treatment, with a focus on SCC, ACC, and other histological types. Different histological types were compared in terms of overall survival, disease-free survival, and progression-free survival. RESULTS: SCC was the most frequently diagnosed histological type (56.2%), followed by ACC (21.3%). Patients with SCC were typically older (78% over 60 years), predominantly male (66%), and associated with smoking. In contrast, the ACC had a more balanced gender distribution and did not correlate with smoking. ACC displayed a significantly better prognosis, with a median overall survival of 129.4 months, compared with 9.0 months for SCC. CONCLUSION: Histological type plays a crucial role in the prognosis of primary tracheal tumors. ACC demonstrated a more favorable outcome compared with SCC.

Impact of PD-L1 Expression on the Overall Survival of Patients With Non-small Cell Lung Cancer Treated With Single-agent Pembrolizumab.

BACKGROUND/AIM: Cemiplimab in patients with non-small cell lung cancer (NSCLC) with PD-L1 (programmed death ligand type 1) expression ≥50% showed a significant improved overall survival (OS) with increasing expression of PD-L1. To our knowledge there exist no similar data published for pembrolizumab regarding the increased OS in relation to the PD-L1 expression. Therefore, the objective of our study was to determine whether improvement in OS reflects increased expression levels of PD-L1 (≥50%) in patients with NSCLC. PATIENTS AND METHODS: Retrospective data from 9 Czech and 1 Polish comprehensive oncology Centers were used. All patients with stage IV NSCLC and PD-L1 expression ≥50% treated with pembrolizumab in daily practice were included. The groups of patients according to the expression of PD-L1 were determined as follows: PD-L1 50-59%, 60-69%, 70-79%, 80-89% and 90-100%. The log-rank test and the Cox regression model were used to compare survival between study groups. RESULTS: A total of 617 patients were included in the study. We did not observe a statistically significant difference in OS between groups of patients with different levels of PD-L1 expression in the pooled comparison (p=0.445). Furthermore, we did not observe a statistically significant difference even when comparing OS in patients with PD-L1expression of 50-59% (reference) with the group of other patients according to the level of expression of PD-L1 in the Cox regression model including the effect covariates. CONCLUSION: PD-L1 expression showed no significant effect on OS in patients with NSCLC with PD-L1≥50% treated with pembrolizumab.

Pembrolizumab-combination therapy for NSCLC- effectiveness and predictive factors in real-world practice.

Introduction: Pembrolizumab combined with chemotherapy has become the standard of care for patients with non-small-cell lung cancer (NSCLC) and the expression of programmed death ligand 1 (PD-L1) in <50% of tumour cells (TC). Methods: We evaluated the efficacy of the treatment in real-world practice, paying attention to the predictive factors, with a special focus on low level of PD-L1 expression. This study is a multicenter retrospective analysis of patients with stage IV NSCLC. Results: A group of 339 consecutive patients was analysed, among them 51% patients with low PD-L1 expression. In the overall population, the ORR was 40.6%, median PFS and OS were 13 months (95% CI 11.4-15) and 16.8 months (95% CI 13.3-20.3), respectively. In multivariate analysis for the entire study population, performance status - ECOG 1 vs. 0 (HR 2.2, 95%CI 1.1-4.6; p=0.02), neutrophil to lymphocyte ratio (NLR)>3 (HR 2.3, 95%CI 1.3-4.2; p=0.04), presence of liver (HR 2.0, 95%CI 1-3.7; p=0. 03) and bone metastases (HR 1.3, 95%CI 1-3; p=0.04), weight loss (HR 1.8, 95%CI 1.1-2.8; p=0.01) and sum of measurable lesions diameters >110 mm (HR 1.7, 95%CI 1-2.9, p=0.049) had a negative impact on OS. Conclusions: In the real world, patients can clinically benefit from immunochemotherapy, regardless of the expression of PD-L1 and the histological type. Other clinicopathological factors such as performance status, extent, and location of secondary lesions have prognostic significance.

The effect of PAMAM dendrimers on the antibacterial activity of antibiotics with different water solubility.

Erythromycin (EM) and tobramycin (TOB) are well-known and widely used antibiotics, belonging to different therapeutic groups: macrolide and aminoglycoside, respectively. Moreover, they possess different solubility: EM is slightly soluble and TOB is freely soluble in water. It was previously demonstrated that PAMAM dendrimers enhanced the pharmacological activity of antifungal drugs by increasing their solubility. Therefore, it appears interesting to investigate the effect of PAMAM-NH2 and PAMAM-OH dendrimers generation 2 (G2) and generation 3 (G3) on the antibacterial activity of antibiotics with different water solubility. In this study it was shown that the aqueous solubility of EM was significantly increased by PAMAM dendrimers (PAMAM-NH2 and PAMAM-OH caused about 8- and 7- fold solubility increases, respectively). However, it was indicated that despite the increase in the solubility, there was only slight influence on the antibacterial activity of EM (2- and 4-fold decreases in the MBC values of EM in the presence of PAMAM-OH G3 and PAMAM-NH2 G2 or G3 for strains of Staphylococcus aureus were noted, respectively). It was also found that there was no influence of PAMAM on the antibacterial activity of hydrophilic TOB.

The Spray-Dried Alginate/Gelatin Microparticles with Luliconazole as Mucoadhesive Drug Delivery System.

Candida species are opportunistic fungi, which are primary causative agents of vulvovaginal candidiasis. The cure of candidiasis is difficult, lengthy, and associated with the fungi resistivity. Therefore, the research for novel active substances and unconventional drug delivery systems providing effective and safe treatment is still an active subject. Microparticles, as multicompartment dosage forms due to larger areas, provide short passage of drug diffusion, which might improve drug therapeutic efficiency. Sodium alginate is a natural polymer from a polysaccharide group, possessing swelling, mucoadhesive, and gelling properties. Gelatin A is a natural high-molecular-weight polypeptide obtained from porcine collagen. The purpose of this study was to prepare microparticles by the spray-drying of alginate/gelatin polyelectrolyte complex mixture, with a novel antifungal drug-luliconazole. In the next stage of research, the effect of gelatin presence on pharmaceutical properties of designed formulations was assessed. Interrelations among polymers were evaluated with thermal analysis and Fourier transform infrared spectroscopy. A valid aspect of this research was the in vitro antifungal activity estimation of designed microparticles using Candida species: C. albicans, C. krusei, and C. parapsilosis. It was shown that the gelatin addition affected the particles size, improved encapsulation efficiency and mucoadhesiveness, and prolonged the drug release. Moreover, gelatin addition to the formulations improved the antifungal effect against Candida species.

Effectiveness of ALK inhibitors in treatment of CNS metastases in NSCLC patients.

Metastases to the central nervous system (CNS) in patients with non-small cell lung cancer constitute an extremely difficult clinical problem, and their occurrence is associated with a poor prognosis. Due to the existence of the blood-brain barrier (BBB) and the action of proteins responsible for the transport of drugs, e.g. P-glycoprotein (P-gp), the penetration of drugs into the CNS is insufficient. Until recently, the only method of CNS metastases treatment was radiotherapy and neurosurgery. The advancement of molecular biology allowed discover targets for molecularly targeted therapies. One of targets is abnormal anaplastic lymphoma kinase, which results from the rearrangement of the ALK gene in patients with non-small cell lung cancer (NSCLC). ALK rearrangement occurs in only about 4.5% of NSCLC patients, but its presence favors brain metastases. The ALK inhibitors (ALKi) were modified to obtain molecules with high ability to penetrate into the CNS. This was achieved by modifying the structure of individual molecules, which became, inter alia, less substrates for P-gp. These modifications caused that less than 10% of patients experience progression in CNS during new ALK inhibitors treatment. This review summarizes the knowledge about the action of BBB, the pharmacodynamics and pharmacokinetics of ALKi, with particular emphasis on their ability to penetrate the CNS and the intracranial activity of individual drugs from different generations of ALK inhibitors.

ALK gene rearrangement favors the development of central nervous system (CNS) metastases in patients with NSCLC. New generations of ALK inhibitors penetrate the CNS and induce an intracranial response and protect against new brain lesions.