Evaluation of polyesteramide (PEA) and polyester (PLGA) microspheres as intravitreal drug delivery systems in albino rats.

PURPOSE: To study the suitability of injectable microspheres based on poly(ester amide) (PEA) or poly lactic-co-glycolic acid (PLGA) as potential vehicles for intravitreal drug delivery in rat eyes. Dexamethasone-loaded PEA microspheres (PEA + DEX) were also evaluated. METHODS: Forty male Sprague Dawley rats were divided into four groups that received different intravitreally injected microspheres: PEA group (n = 12); PLGA group (n = 12); PEA + DEX group (n = 8); and control group (no injection, n = 8). Electroretinography (ERG), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (sdOCT) were performed at baseline, weeks 1 and 2, and months 1, 2, and 3 after intravitreal injection. Eyes were histologically examined using light microscopy and transmission electron microscopy at the end of the in vivo study. RESULTS: There were no statistically significant changes in ERG among the groups. Abnormal FAF pattern and abnormal deposits in OCT were observed after injection but almost completely disappeared between week 2 and month 3 in all injected groups. GFAP staining showed that Müller glia cell activation was most pronounced in PLGA-injected eyes. Increased cell death was not observed by TUNEL staining at month 1. In electron microscopy at month 3, the remnants of microparticles were found in the retinal cells of all injected groups, and loss of plasma membrane was seen in the PLGA group. CONCLUSIONS: Although morphological changes such as mild glial activation and material remnants were observed histologically 1 month and 3 months after injection in all injected groups, minor cell damage was noted only in the PLGA group at 3 months after injection. No evidence of functional abnormality relative to untreated eyes could be detected by ERG 3 months after injection in all groups. Changes observed in in vivo imaging such as OCT and FAF disappeared after 3 months in almost all cases.

Novel biodegradable polyesteramide microspheres for controlled drug delivery in Ophthalmology.

Most of the posterior segment diseases are chronic and multifactorial and require long-term intraocular medication. Conventional treatments of these pathologies consist of successive intraocular injections, which are associated with adverse effects. Successful therapy requires the development of new drug delivery systems able to release the active substance for a long term with a single administration. The present work involves the description of a new generation of microspheres based on poly(ester amide)s (PEA), which are novel polymers with improved biodegradability, processability and good thermal and mechanical properties. We report on the preparation of the PEA polymer, PEA microspheres (PEA Ms) and their characterization. PEA Ms (~15µm) were loaded with a lipophilic drug (dexamethasone) (181.0±2.4µg DX/mg Ms). The in vitro release profile of the drug showed a constant delivery for at least 90days. Based on the data from a performed in vitro release study, a kinetic ocular model to predict in vivo drug concentrations in a rabbit vitreous was built. According to the pharmacokinetic simulations, intravitreal injection of dexamethasone loaded PEA microspheres would provide release of the drug in rabbit eyes up to 3months. Cytotoxicity studies in macrophages and retinal pigment epithelial cells revealed a good in vitro tolerance of the microsystems. After sterilization, PEA Ms were administered in vivo by subtenon and intravitreal injections in male Sprague-Dawley rats and the location of the microspheres in rat eyes was monitored. We conclude that PEA Ms provide an alternative delivery system for controlling the delivery of drugs to the eye, allowing a novel generation of microsphere design.

The effect of integrated health management model on the health of older adults with diabetes in a randomized controlled trial.

The objective of this study was to evaluate the effect of integrated health management model on the health of older adults with diabetes. The 100 older adults with diabetes who gave informed consent were randomly allocated 1:1 into management and control groups. The integrated health management model was applied in the former while the latter was only given usual care. This model included the following components: health record establishment, health evaluation and health management (such as: diet advice, psychological aspects of health, education/skills training on health self-management, regular blood glucose monitoring, long-term diabetes drug monitoring, etc.). After 18 months, differences in three categories of variables (subjective grading items, objective measurement health indices and health service utilization) between the two groups before and after the intervention were assessed with t-test, χ(2)-test and mixed model analysis. The management group demonstrated improvement on the following variables: health knowledge score, self-evaluated psychological conditions, overall self-evaluated health conditions, diet score, physical activity duration per week, regular blood sugar monitoring, waist-to-hip ratio, diastolic blood pressure and fasting blood sugar, the days of hospital admissions in the preceding 6 months. Mixed model analysis showed that gender, age, self-evaluated health status, self-evaluated psychological status, education level and resident status were important factors affecting health indices. This study demonstrated that integrated health management model was effectiveness in improving the health of older adults with diabetes.

The long-term effect of community-based health management on the elderly with type 2 diabetes by the Markov modeling.

The aim of this study was to assess the long-term effects of community-based health management on elderly diabetic patients using a Markov model. A Markov decision model was used to simulate the natural history of diabetes. Data were obtained from our randomized trials of elderly with type 2 diabetes and from the published literature. One hundred elderly patients with type 2 diabetes were randomly allocated to either the management or the control group in a one-to-one ratio. The management group participated in a health management program for 18 months in addition to receiving usual care. The control group only received usual care. Measurements were performed on both groups at baseline and after 18 months. The Markov model predicted that for every 1000 diabetic patients receiving health management, approximately 123 diabetic patients would avoid complications, and approximately 37 would avoid death over the next 13 years. The results suggest that the health management program had a positive long-term effect on the health of elderly diabetic patients. The Markov model appears to be useful in health care planning and decision-making aimed at reducing the financial and social burden of diabetes.

Dispersion polymerisation in supercritical CO2 using macro-RAFT agents.

Fluorinated macro-RAFT agents can act as in situ stabilisers while exhibiting good control over block copolymers formed by dispersion polymerisation in supercritical CO2 to yield well-defined spherical particles with a fluorinated "halo".

Successful dispersion polymerization in supercritical CO2 using polyvinylalkylate hydrocarbon surfactants synthesized and anchored via RAFT.

New CO2-philic hydrocarbon molecules were synthesized by reversible addition fragmentation chain-transfer polymerization. These poly(vinyl alkylates) show the highest solubility in supercritical CO2 of any hydrocarbon reported to date. By utilizing the anchoring ability of the thiocarbonylthio end group, the dispersion polymerization of N-vinyl pyrrolidone was successfully achieved in scCO2 leading to high yields of well-defined spherical polymer particles.