Elisa J. Campos

Design and characterization of bi-soft segmented polyurethane microparticles for biomedical application.

Bi-soft segmented poly(ester urethane urea) microparticles were prepared and characterized aiming a biomedical application. Two different formulations were developed, using poly(propylene glycol), tolylene 2,4-diisocyanate terminated pre-polymer (TDI) and poly(propylene oxide)-based tri-isocyanated terminated pre-polymer (TI). A second soft segment was included due to poly(ɛ-caprolactone) diol (PCL). Infrared spectroscopy, used to study the polymeric structure, namely its H-bonding properties, revealed a slightly higher degree of phase separation in TDI-microparticles. TI-microparticles presented slower rate of hydrolytic degradation, and, accordingly, fairly low toxic effect against macrophages. These new formulations are good candidates as non-biodegradable biomedical systems.

Polyurethane-based microparticles : Formulation and influence of processes variables on its characteristics

This study reports the development of polyurethane-based microparticles and the influence of some processes variables on its characteristics. These microparticles were prepared by emulsion polymerization, using poly(caprolactone) diol (PCL) and poly(propylene glycol), tolylene 2,4-diisocyanate terminated (TDI) or poly(propylene oxide)-based tri-isocyanated pre-polymer (TI). The reaction of polymerization was confirmed by attenuated total internal reflection Fourier transformed infrared spectroscopy (ATR-FTIR). Their thermal characteristics were investigated by dynamical mechanical thermal analysis (DMTA) and thermogravimetric analysis (TGA). For good microparticles formation, formulation 80/20 (mass ratio isocyanate/PCL) was the most indicated. Their spherical shape and smooth surface were observed by optical and scanning electron microscopy (SEM). Zeta potential measurements suggest that ionized carbonyl groups existent at the surface can be responsible for the negative potentials obtained. Respecting size and size distribution of the particles, measured by laser diffraction spectroscopy (LDS), the stirring speed and type were the process variables that most influenced it.

Viewing the choroid: where we stand, challenges and contradictions in diabetic retinopathy and diabetic macular oedema

Diabetic macular oedema (DMO) is the leading cause of vision loss in the working‐age population. Blood–retinal barrier (BRB) dysfunction in diabetic retinopathy (DR), mainly at the level of the retinal vessels, has long been related with leakage and fluid accumulation, leading to macular oedema. However, the nourishment of the macula is provided by the choroid and a diabetic choroidopathy has been described. Therefore, there has been a growing interest in studying the role of the choroid in the pathophysiology of DR and DMO, mainly by optical coherence tomography (OCT). Nevertheless, there are conflicting results in the different studies. We summarize the results from the available studies, describe the limitations and confounding factors and discuss future procedures to avoid bias.

Opening eyes to nanomedicine: Where we are, challenges and expectations on nanotherapy for diabetic retinopathy

People affected with ocular diseases will significantly increase over the next decades, and, consequently, a substantial increase in health costs is expected. Diabetic retinopathy is the most common chronic complication of diabetes. The treatment of eye diseases affecting the posterior segment, such as diabetic retinopathy, is quite challenging due to the anatomy, physiology and biochemistry of the eye. Therefore, the development of new therapeutics for posterior eye diseases has been a major focus of pharmaceutical research in the area of vision sciences. Several nanosystems already offer efficient solutions for ophthalmological conditions, targeting internal eye tissues, as the retina, and many novel products are expected to appear hereafter. This review provides an insight on nanoparticle-based solutions for therapies directed to posterior segment of the eye diseases, particularly diabetic retinopathy, the present scenario, and the demands and expectations for the future.

Response to: Choroidal thickness changes stratified by outcome in real-world treatment of diabetic macular edema

1. The authors considered the following, as possible bias, in our study, (i) about half of the population had past laser history; (ii) different forms of non-proliferative diabetic retinopathy (NPDR) were included; (iii) the eyes that developed proliferative diabetic retinopathy, the eyes that were rescued by laser or switched to steroids were excluded from the follow-up, and (iv) 13 eyes were treated with aflibercept. 2. Previously, we stated that it is under dispute how choroidal thickness (CT) changes with the NPDR staging, but not with the anti-VEGF use, in any form of NPDR [1]. Supplementary Fig. 2 depicts that differences in CT regarding past laser history were not significant. Outcome calculations were done at 6 months (M). At this time point, none of the eyes were excluded from the followup, due to the aforementioned circumstances. Aflibercept and ranibizumab are very similar drugs in the treatment of DME. It is known that, differences in the outcome, at year 1, were only observed for patients with visual acuity (VA) ≤ 20/50 [2]. Accordingly, we treated the eyes with aflibercept strictly in the same range of VA. If aflibercepttreated eyes were expected to have a better outcome and if SFCT would be a marker of outcome, it would be pointless to this relative relation which drug were to be used. Moreover, there is some controversy about the first year results of the Protocol T study and patients with VA ≤ 20/ 50 had better functional outcome but had no significant differences in the baseline central retinal thinness (CRT) [3, 4]. 3. The authors referred to the Bproportion of eyes that sustained retinal dryness at the end of the study.^ Let us recall that the anatomic response had a specific criterion and that outcome measures were made at 6 M. 4. The authors appeal to prognostic factors of DME, including 11 factors. They missed several others, such as age, hypertension, gender, duration of diabetes, laser history, Hb A1c, hyper-reflective spots (HRS), photoreceptor outer segment (PROS) length, predominantly peripheral lesions (PPLs), SFCT, CRT, and VA. Actually, one may find over 30 factors that may influence DME prognosis, making multivariate linear regressionmeaningless, as overlapping would be unavoidable and independence would be lost. Nevertheless, we analyzed 12 prognostic factors, in real-world treatment of DME, to be published in another study. Baseline SFCT was not found to be predictive in the multivariate linear regression model, either. Furthermore, several OCT prognostic factors of DME were compared and recently published by one of the authors of our report [5]. 5. The authors concluded that, after 6 M, 79.3% of the eyes were switched to other treatments. This is an incorrect conclusion. Actually, only two eyes were treated with PRP, after the 12M of follow-up, and 6 other were treated * António Campos acamposoft@gmail.com

Impact of type 1 diabetes mellitus and sitagliptin treatment on the neuropeptide Y system of rat retina: The neuropeptide Y system in the retina

Neuropeptide Y (NPY) is a neuromodulator that is expressed in the retina. Increasing evidence suggests that NPY has pronounced anti‐inflammatory effects, which might depend on the inhibition of dipeptidyl‐peptidase‐IV (DPP‐IV). The aim of this study was to investigate the impact of type 1 diabetes mellitus (DM) and sitagliptin, a DPP‐IV inhibitor, on the NPY system in the retina using an animal model.