Pharmaceutical approaches based on nanotechnologies and the development of eye drops composed of the mucoadhesive polymers chitosan and hyaluronic acid are emerging strategies for the efficient ...treatment of ocular diseases. These innovative nanoparticulate systems aim to increase drugs' bioavailability at the ocular surface. For the successful development of these systems, the evaluation of mucoahesiveness (the interaction between the ocular delivery system and mucins present on the eye) is of utmost importance. In this context, the aim of the present work was to investigate the mucoadhesivity of a novel nanoparticle eye drop formulation containing an antibiotic (ceftazidime) intended to treat eye infections. Eye drop formulations comprised a polymer (hydroxypropyl) methyl cellulose (HPMC) 0.75% (
/
) in an isotonic solution incorporating chitosan/sodium tripolyphosphate (TPP)-hyaluronic acid-based nanoparticles containing ceftazidime. The viscosity of the nanoparticles, and the gels incorporating the nanoparticles were characterized in contact with mucin at different mass ratios, allowing the calculation of the rheological synergism parameter (∆η). Results showed that at different nanoparticle eye formulation:mucin weight ratios, a minimum in viscosity occurred which resulted in a negative rheological synergism. Additionally, the results highlighted the mucoadhesivity of the novel ocular formulation and its ability to interact with the ocular surface, thus increasing the drug residence time in the eye. Moreover, the in vitro release and permeation studies showed a prolonged drug release profile from the chitosan/TPP-hyaluronic acid nanoparticles gel formulation. Furthermore, the gel formulations were not cytotoxic on ARPE-19 and HEK293T cell lines, evaluated by the metabolic and membrane integrity tests. The formulation was stable and the drug active, as shown by microbiological studies. In conclusion, chitosan/TPP-hyaluronic acid nanoparticle eye drop formulations are a promising platform for ocular drug delivery with enhanced mucoadhesive properties.
The rapid spread of Zika virus in the Americas and current outbreak of microcephaly in Brazil has raised attention to the possible deleterious effects that the virus may have on fetuses.
We report a ...case of a 20-year-old pregnant woman who was referred to our service after a large Zika virus outbreak in the city of Salvador, Brazil with an ultrasound examination that showed intrauterine growth retardation of the fetus at the 18th gestational week. Ultrasound examinations in the 2nd and 3rd trimesters demonstrated severe microcephaly, hydranencephaly, intracranial calcifications and destructive lesions of posterior fossa, in addition to hydrothorax, ascites and subcutaneous edema. An induced labor was performed at the 32nd gestational week due to fetal demise and delivered a female fetus. ZIKV-specific real-time polymerase chain reaction amplification products were obtained from extracts of cerebral cortex, medulla oblongata and cerebrospinal and amniotic fluid, while extracts of heart, lung, liver, vitreous body of the eye and placenta did not yield detectable products.
This case report provides evidence that in addition to microcephaly, there may be a link between Zika virus infection and hydrops fetalis and fetal demise. Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes.
Abstract During the past decade, the number of studies describing nanostructured lipid carriers (NLCs)-based formulations has been dramatically increased. The raise in NLC exploitation is essentially ...due to defeated barriers within the technological process of lipid-based nanoparticles’ formulation and increased knowledge of the underlying mechanisms of transport of NLCs via different routes of administration. This review article aims to give an overview on the current state of the art of NLC as controlled drug delivery systems for future clinics through novel NLC applications providing examples of successfull outcomes. The reported data clearly illustrate the promise of these nanoparticles for novel treatments in the near future. From the Clinical Editor The understanding of the nanostructured lipid carriers (NLC)-based formulations has improved with continuing research recently. The result has seen an increase in the use of these in the clinical setting. In this comprehensive review, the authors discussed the current state and major challenges in the use of nanostructured lipid carriers as controlled drug delivery systems.
To describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age. We followed children with CZS-associated ...microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively. Of the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (beta = 0.29; CI 95% = 0.02-0.57) and motor raw scores (beta = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (beta = 1.27; CI 95% = 0.01-2.53) and motor raw scores (beta = 2.03; CI 95% = 0.25-3.81). Children with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.
The aim of the present study was to develop novel Mycobacterium bovis bacille Calmette-Guérin (BCG)-loaded polymeric microparticles with optimized particle surface characteristics and ...biocompatibility, so that whole live attenuated bacteria could be further used for pre-exposure vaccination against Mycobacterium tuberculosis by the intranasal route. BCG was encapsulated in chitosan and alginate microparticles through three different polyionic complexation methods by high speed stirring. For comparison purposes, similar formulations were prepared with high shear homogenization and sonication. Additional optimization studies were conducted with polymers of different quality specifications in a wide range of pH values, and with three different cryoprotectors. Particle morphology, size distribution, encapsulation efficiency, surface charge, physicochemical properties and biocompatibility were assessed. Particles exhibited a micrometer size and a spherical morphology. Chitosan addition to BCG shifted the bacilli surface charge from negative zeta potential values to strongly positive ones. Chitosan of low molecular weight produced particle suspensions of lower size distribution and higher stability, allowing efficient BCG encapsulation and biocompatibility. Particle formulation consistency was improved when the availability of functional groups from alginate and chitosan was close to stoichiometric proportion. Thus, the herein described microparticulate system constitutes a promising strategy to deliver BCG vaccine by the intranasal route.
Abstract Lung cancer remains a leading cause of death due to the low efficacy of chemotherapy, mainly related to the administration route used. Therefore, alternative administration routes are ...needed. Paclitaxel (PTX) is an insoluble anticancer drug active against solid tumors, such as those found in lung cancer, that has stimulated an intense research effort over recent years. Solid lipid nanoparticles (SLNs) are potential carriers for poorly soluble drugs, being biodegradable systems that served as alternatives to the usual colloidal carriers. That system was used to deliver PTX to the lungs and seem to fulfill the requirements for an optimum particulate carrier. Furthermore, PTX-loaded SLN pulmonary administration provided a target administration, which is expected to avoid high concentration of the drug at nontarget tissues, reducing toxicity, and increasing the drug's therapeutic index. The rationale of this study was to deliver a colloidal system to the lung lymphatics through a pulmonary route for cancer therapy. From the Clinical Editor Paclitaxel-loaded solid lipid nanoparticles were used to target tumors in a murine lung cancer model enabling high PTX concentration in the target with reduced systemic toxicity and increased therapeutic index.
The prevalence of developmental alterations associated with in-utero Zika virus (ZIKV) exposure in children is not well understood. Furthermore, estimation of the Population Attributable Fraction ...(PAF) of developmental alterations attributed to ZIKV has not been performed due to lack of population-based cohorts with data on symptomatic and asymptomatic ZIKV exposures and an appropriate control group. The aim of this study was to characterize neurodevelopmental outcomes of children at 11 to 32 months of age with intrauterine ZIKV exposure and estimate the PAF of alterations secondary to ZIKV exposure.
We performed a cohort of biannual community-based prospective serosurveys in a slum community in Salvador, Brazil. We recruited women participating in our cohort, with a documented pregnancy from January 2015 to December 2016 and children born to those mothers. Children were classified as ZIKV exposed in utero (born from women with ZIKV seroconversion during pregnancy) or unexposed (born from women without ZIKV seroconversion or that seroconverted before/after pregnancy) by using an IgG monoclonal antibody blockade-of-binding (BoB). We interviewed mothers and performed anthropometric, audiometric, ophthalmological, neurologic, and neurodevelopmental evaluations of their children at 11 to 32 months of age. Among the 655 women participating in the cohort, 66 (10%) were pregnant during the study period. 46 (70%) of them completed follow-up, of whom ZIKV seroconversion occurred before, during, and after pregnancy in 25 (54%), 13 (28%), and 1 (2%), respectively. The rest of women, 7 (21.2%), did not present ZIKV seroconversion. At 11 to 32 months of life, the 13 ZIKV-exposed children had increased risk of mild cognitive delay (RR 5.1; 95%CI 1.1-24.4) compared with the 33 children unexposed, with a PAF of 53.5%. Exposed children also had increased risk of altered auditory behavior (RR 6.0; 95%CI 1.3-26.9), with a PAF of 59.5%.
A significant proportion of children exposed in utero to ZIKV developed mild cognitive delay and auditory behavioral abnormalities even in the absence of gross birth defects such as microcephaly and other neurodevelopmental domains. Furthermore, our findings suggest that over half of these abnormalities could be attributed to intrauterine ZIKV exposure.
Theranostics has emerged in recent years to provide an efficient and safer alternative in cancer management. This review presents an updated description of nanotheranostic formulations under ...development for skin cancer (including melanoma), head and neck, thyroid, breast, gynecologic, prostate, and colon cancers, brain-related cancer, and hepatocellular carcinoma. With this focus, we appraised the clinical advantages and drawbacks of metallic, polymeric, and lipid-based nanosystems, such as low invasiveness, low toxicity to the surrounding healthy tissues, high precision, deeper tissue penetration, and dosage adjustment in a real-time setting. Particularly recognizing the increased complexity and multimodality in this area, multifunctional hybrid nanoparticles, comprising different nanomaterials and functionalized with targeting moieties and/or anticancer drugs, present the best characteristics for theranostics. Several examples, focusing on their design, composition, imaging and treatment modalities, and in vitro and in vivo characterization, are detailed herein. Briefly, all studies followed a common trend in the design of these theranostics modalities, such as the use of materials and/or drugs that share both inherent imaging (e.g., contrast agents) and therapeutic properties (e.g., heating or production reactive oxygen species). This rationale allows one to apparently overcome the heterogeneity, complexity, and harsh conditions of tumor microenvironments, leading to the development of successful targeted therapies.
Telomere Length and Pesticide Residues in Food: A Causal Link? Scorza, Fulvio A.; Finsterer, Josef; Beltramim, Larissa ...
Journal of the Academy of Nutrition and Dietetics,
March 2024, 2024-03-00, 20240301, Letnik:
124, Številka:
3
Journal Article
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