RESUMEN

The importance of the conjunctival/scleral pathway as a route of entry into the ciliary body, and in particular uptake and deposition by vessels, was investigated. A constant concentration of methazolamide analogs as well as 6-carboxyfluorescein (6-CB) and rhodamine B (RB) was maintained on either the cornea or the conjunctiva/sclera tissue, the latter excluding the cornea. The solutions were applied with the use of a cylindrical well affixed to the cornea of an anesthetized white rabbit. After two hours, concentrations of drug or dye were measured in cornea, aqueous humor or iris/ciliary body for both routes of entry. Confocal microscopy methods were used to determine reflected fluorescence images for 6-CB and RB. Carbonic anhydrase inhibition, partitioning, solubility and intraocular pressure (IOP) measurements were also determined. Permeability calculations were estimated for drug diffusing against aqueous flow within the posterior chamber. The conjunctival/scleral route of entry produced higher iris/ciliary body concentrations for all compounds except for the lipophilic RB. Confocal microscopy results suggested that drug is gaining entry into the ciliary body through vessel uptake in the sclera. Following entry of drug into the conjunctival/scleral tissue, a significant portion enters scleral vessels and deposits within the ciliary body. Calculations are given that indicate that once drug penetrates the cornea it is highly unlikely drug diffuses through the pupil against aqueous flow to enter the posterior chamber and reach the ciliary body.

Asunto(s)

RESUMEN

We have studied the controlled release of proteins from poly(sucrose acrylate) hydrogels. The hydrogels were prepared by a two-step procedure in which sucrose was first acylated to sucrose-1'-acrylate followed by free radical polymerization. By adjusting the cross-link ratio and initial monomer concentration, the swelling ratio of the hydrogel was varied from five to 28. The mechanical strength of these hydrogels was comparable to that of the hydrogels with approximately the same swelling ratio. Scanning electron micrographs and mesh size calculations indicate that the hydrogel is macroporous, suggesting it may be suitable for a variety of biomedical applications. The release kinetics of beta-lactoglobulin, bovine serum albumin and gamma-globulin were studied as a function of initial monomer concentrations for the sucrose-based hydrogel. All of the release profiles were characterized by an initial burst of protein in the first 25 h followed by a long period of sustained release (> 500 h). The magnitude of the initial burst was reduced by increasing the initial monomer concentration and by increasing the molecular weight of the protein. A quantitative model based on the heterogeneous nature of hydrogel was developed to explain the observed release kinetics.

Asunto(s)

RESUMEN

The M(r) values of pharmaceutical heparins and low-molecular-weight (LMW) heparin derivatives were examined as part of a collaborative study to develop methods for their characterization. Standard methods of M(r) determination rely on gel permeation high-performance liquid chromatography (HPLC). We report the use of gradient polyacrylamide gel electrophoresis (PAGE) to determine the M(r) values of pharmaceutical heparins and LMW heparin derivatives. This approach offers certain advantages over the HPLC method. Gradient PAGE analysis was performed in parallel, on multiple samples, with the same standard curve. HPLC was performed serially. Gradient PAGE gave higher resolution than HPLC, and thus, a mixture of easily obtained standards was used in place of individual standards for the construction of a standard curve. Heparin and various LMW heparin samples were analyzed by both gradient PAGE and conventional gel permeation HPLC methods. The number-average M(r), weight-average M(r), and polydispersity were examined by both techniques and found to be similar. This study demonstrates that gradient PAGE analysis is a sensitive method for the determination of the M(r) values of heparin and LMW heparin.

Asunto(s)

RESUMEN

A variety of enzymes have been found to acylate sucrose in anhydrous pyridine. The enzymic reaction is highly selective; with trifluoroethylbutyrate as ester donor, enzyme-catalyzed transesterification of sucrose yielded sucrose 1'-butyrate and sucrose 6, 1'-dibutyrate. No sucrose-tributyrates were formed. Using a similar technique, a long-chain linear sucrose polyester has been prepared using Proleather, an alkaline protease from a Bacillus sp. This protease catalyzes the esterification of sucrose with bis(2, 2, 2-trifluoroethyladipate) in a 1:1 ratio to yield a sucrose-containing polyester with M(w) = 2100 and M(n) = 1600 for a polydispersity of 1. 31. Polymers with molecular weights in excess of 13, 000 have been prepared by this enzymic approach, indicating that molecules containing over 30 sucrose units have been produced. The polyester is extremely water soluble and soluble in polar organic solvents. As with the sucrose dibutyrate, the polyester has ester linkages at the C6 and C1' positions on the sucrose. The polyester can be depolymerized using Proleather in aqueous buffer, pH7. After 9 days in aqueous buffer, Proleather catalyzed the breakdown of the polyester to an M(w) of ca. 900. This sucrose-containing polyester may have applications as a water-absorbent, biodegradable plastic for use as diapers and hygienic products, water-treatment chemicals, and components of drug delivery systems.