Polymeric Micelles in Ocular Drug Delivery: Rationale, Strategies and Challenges

Polymeric micelles that can deliver drug to intended sites of the eye have attracted much scientific attention recently. The aim here is to review the aqueous-based formulation of drug loaded polymeric micelles that hold significant promise for ophthalmic drug delivery. These innovative nanosystems can provide the biopharmaceutical advantages of higher permeation and enhancement of residence time at ocular surface for better drug absorption through ocular barriers. Mucoadhesive properties of biopolymers forming micelle enhance their contact time and minimize their elimination from the absorbing surface, consequently increasing the bioavailability of the drug. Their physicochemical characteristics are also important with respect to the industrial production and patient compliance. Drug loaded polymeric micelles can be fabricated by simple and cost effective techniques with improved physical stability which fulfils the requirements for industrial acceptance. Innovative polymeric micelle formulations allow their easy application in the form of eye drops without blurring of vision and discomfort, thus achieving patient compliance requirements

Spray-driedMicrospheres Based on Chitosan and LecithinCyclosporin A Delivery System

Conventional and composed cyclosporin A (CsA)-loaded polymeric microspheres (MS) were prepared by spray-drying of CsA/chitosan one-phase system (solutions) and CsA/lecithin/chitosan two-phase system (suspensions). Microspheres were characterised in terms of production yield, entrapment efficiency, size distribution, zeta-potential, thermal properties, swelling ability and drug release profile. Conventional MS were characterised by mean diameter ranging from 1.15 ± 0.91 to 1.27 ± 0.84 m and CsA entrapment efficiency varying from 72.6 to 87.3%. Composed MS were characterised by larger mean diameter (1.32 ± 1.08 to 1.53 ± 1.15 m) and higher CsA entrapment efficiency (86.6–94.3%) compared to the corresponding conventional MS. Only composed MS showed swelling ability, which was proportional to chitosan base content in the preparation. In vitro CsA release profile depended on both, the type of the spray-dried system and the chitosan used, as these factors were crucial in determining CsA entrapment pattern and swelling/dissolution ability of MS

Spray-driedMicrospheres Based on Chitosan and LecithinCyclosporin A Delivery System

Conventional and composed cyclosporin A (CsA)-loaded polymeric microspheres (MS) were prepared by spray-drying of CsA/chitosan one-phase system (solutions) and CsA/lecithin/chitosan two-phase system (suspensions). Microspheres were characterised in terms of production yield, entrapment efficiency, size distribution, zeta-potential, thermal properties, swelling ability and drug release profile. Conventional MS were characterised by mean diameter ranging from 1.15 ± 0.91 to 1.27 ± 0.84 m and CsA entrapment efficiency varying from 72.6 to 87.3%. Composed MS were characterised by larger mean diameter (1.32 ± 1.08 to 1.53 ± 1.15 m) and higher CsA entrapment efficiency (86.6–94.3%) compared to the corresponding conventional MS. Only composed MS showed swelling ability, which was proportional to chitosan base content in the preparation. In vitro CsA release profile depended on both, the type of the spray-dried system and the chitosan used, as these factors were crucial in determining CsA entrapment pattern and swelling/dissolution ability of MS

Prevalence, prenatal screening and neonatal features in children with Down syndrome: a registry-based national study

BACKGROUND: Down syndrome (DS) is one of the most common chromosomal abnormalities among newborns. In recent years advances in perinatal and neonatal care have improved chance of survival for the children with DS. The objective of this Registry-Based study was to get more accurate data of DS prevalence with evaluation of antenatal screening, neonatal and maternal features among total births in Croatia from 2009 to 2012. ----- METHODS: We used retrospectively collected data for DS newborns from the medical birth database and perinatal mortality database for the period of 2009-2012. Differences between DS and the referent population for each year in quantitative measures were assessed with the independent t-test. Other differences in nominal and categorical values were analyzed with the chi-square test. ----- RESULTS: The total prevalence for DS in the period of 2009-2012 was 7.01 per 10,000 births, while the live-birth prevalence was 6.49 per 10,000 births. The significant differences (p < 0.05) between the DS and reference populations for each year were noticed for birth weight and length, gestational age, mother age, Apgar score of ≥6 after 5 min and breastfeeding. Among newborns with DS, there were 64 (53.33 %) males and 56 (46.67 %) females versus 88,587 (51.76 %) males and 82,553 (48.23 %) females in the reference population. In the DS group compared to the reference population the mean birth weight was 2845 grams versus 3467 grams in males and 2834 grams versus 3329 grams in females, respectively, with a mean birth length of 47 cm versus 50 cm for both genders. The mean gestational age of the DS births was 37 weeks and the mean age of the mothers was 32.6 years, versus 39 weeks and 29.1 years, respectively, in the reference population. Only 68.3 % of children with DS were breastfed from birth, compared with 94.72 % of children in the reference population. ----- CONCLUSIONS: The significant differences for neonatal and maternal features between DS and the referent population were found similar to other studies. The total prevalence of DS in Croatia in the period of 2009-2012 was lower than the previously estimated prevalence based on EUROCAT data. The establishment of a new national registry of congenital malformations covering 99 % of all births in Croatia is necessary to improve the health and prosperity of children, adolescents and adults with DS in Croatia

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection

Using Robson's Ten‐Group Classification System for comparing caesarean section rates in Europe: an analysis of routine data from the Euro‐Peristat study

Objective Robson's Ten Group Classification System (TGCS) creates clinically relevant sub‐groups for monitoring caesarean birth rates. This study assesses whether this classification can be derived from routine data in Europe and uses it to analyse national caesarean rates. Design Observational study using routine data. Setting Twenty‐seven EU member states plus Iceland, Norway, Switzerland and the UK. Population All births at ≥22 weeks of gestational age in 2015. Methods National statistical offices and medical birth registers derived numbers of caesarean births in TGCS groups. Main outcome measures Overall caesarean rate, prevalence and caesarean rates in each of the TGCS groups. Results Of 31 countries, 18 were able to provide data on the TGCS groups, with UK data available only from Northern Ireland. Caesarean birth rates ranged from 16.1 to 56.9%. Countries providing TGCS data had lower caesarean rates than countries without data (25.8% versus 32.9%, P = 0.04). Countries with higher caesarean rates tended to have higher rates in all TGCS groups. Substantial heterogeneity was observed, however, especially for groups 5 (previous caesarean section), 6, 7 (nulliparous/multiparous breech) and 10 (singleton cephalic preterm). The differences in percentages of abnormal lies, group 9, illustrate potential misclassification arising from unstandardised definitions. Conclusions Although further validation of data quality is needed, using TGCS in Europe provides valuable comparator and baseline data for benchmarking and surveillance. Higher caesarean rates in countries unable to construct the TGCS suggest that effective routine information systems may be an indicator of a country's investment in implementing evidence‐based caesarean policies. Tweetable abstract Many European countries can provide Robson's Ten‐Group Classification to improve caesarean rate comparisons

Melatonin-loaded lecithin/chitosan nanoparticles: Physicochemical characterisation and permeability through Caco-2 cell monolayers

In this study, the potential of lecithin/chitosan nanoparticles (NPs) as a mucoadhesive colloidal nanosystem for transmucosal delivery of melatonin was investigated. The size, zeta potential and melatonin loading of the lecithin/chitosan NPs were investigated as a function of lecithin type (Lipoid S45, S75 and S100) and chitosan content in the preparation. The NPs were characterised by mean diameter and zeta potential ranging between 121.6 and 347.5 nm, and 7.5 and 32.7 mV, respectively, and increasing with lecithin-negative charge and chitosan content in the preparation. Melatonin loadings were up to 7.1%. All NPs were characterised by prolonged release profiles with an initial burst (approximately 25%), followed by a slowrelease phase. Approximately 60\u201370% of melatoninwas released in 4 h. The permeability of melatonin was investigated using Caco-2 cells as an in vitro model of the epithelial barrier