On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein

Overcoming the natural defensive barrier functions of the eye remains one of the greatest challenges of ocular drug delivery. Cornea is a chemical and mechanical barrier preventing the passage of any foreign bodies including drugs into the eye, but the factors limiting penetration of permeants and nanoparticulate drug delivery systems through the cornea are still not fully understood. In this study, we investigate these barrier properties of the cornea using thiolated and PEGylated (750 and 5000 Da) nanoparticles, sodium fluorescein, and two linear polymers (dextran and polyethylene glycol). Experiments used intact bovine cornea in addition to bovine cornea de-epithelialized or tissues pretreated with cyclodextrin. It was shown that corneal epithelium is the major barrier for permeation; pretreatment of the cornea with β-cyclodextrin provides higher permeation of low molecular weight compounds, such as sodium fluorescein, but does not enhance penetration of nanoparticles and larger molecules. Studying penetration of thiolated and PEGylated (750 and 5000 Da) nanoparticles into the de-epithelialized ocular tissue revealed that interactions between corneal surface and thiol groups of nanoparticles were more significant determinants of penetration than particle size (for the sizes used here). PEGylation with polyethylene glycol of a higher molecular weight (5000 Da) allows penetration of nanoparticles into the stroma, which proceeds gradually, after an initial 1 h lag phase

Preparation and characterization of hydrogels with potential for use as biomaterials

Hydrogels have been extensively explored for biomedical applications due to their ability to absorb high water content in its structure, which gives excellent biocompatibility. This work aims at obtaining biocompatible hydrogels with potential for use in increasing the mechanical strength of bone substitutes, or controlled drug release. Poly (N-vinyl-2-pyrrolidone) hydrogels were prepared by free radical polymerization with and without the addition of acrylic acid. Azobisisobutyronitrile and ammonium persulfate were used as initiator and N,N-methylenebisacrylamide was used as the crosslinking agent. The characterization of the hydrogels was performed by thermogravimetric analysis, differential scanning calorimetry, infrared spectroscopy and swelling properties. The results obtained demonstrate different degrees of crosslinking and swelling of up to 490 ± 30%. The different properties of the hydrogels suggest different applications

Synthesizing certified code

Abstract. Code certification is a lightweight approach for formally demonstrating software quality. Its basic idea is to require code producers to provide formal proofs that their code satisfies certain quality properties. These proofs serve as certificates that can be checked independently. Since code certification uses the same underlying technology as program verification, it requires detailed annotations (e.g., loop invariants) to make the proofs possible. However, manually adding annotations to the code is time-consuming and error-prone. We address this problem by combining code certification with automatic program synthesis. Given a high-level specification, our approach simultaneously generates code and all annotations required to certify the generated code. We describe a certification extension of AutoBayes, a synthesis tool for automatically generating data analysis programs. Based on built-in domain knowledge, proof annotations are added and used to generate proof obligations that are discharged by the automated theorem prover E-SETHEO. We demonstrate our approach by certifying operator- and memory-safety on a data-classification program. For this program, our approach was faster and more precise than PolySpace, a commercial static analysis tool