Cross-linking Duration Research Articles

Mechanical properties of layered poly(ethylene glycol) gels

Poly(ethylene glycol) (PEG) hydrogels have become a popular material for biomedical applications because of their versatility in use and design. As these gels are readily crosslinked under UV, microfabrication techniques have been investigated to manufacture complex three dimensional structures to better mimic the in vivo environment. This work investigated whether a layering technique to fabricate gels offered sufficient strength between the layers to perform similarly in mechanical testing to unlayered gels. Two mechanical tests were performed: tensile tests and peel tests. The tensile tests, which examined sample gels whose test sections were crosslinked for different durations, demonstrated no statistical differences in elastic modulus between sample and control gels. As expected, a statistical increase in the elastic modulus was found with increased PEG concentration. Comparison of the yield stress between samples and controls illustrated differences with total crosslinking duration, which may be due to the decreased molecular weight of the chains with decreased crosslinking time. In peel tests, no statistical differences of maximum peel force were found between samples and controls. However, an increase in the maximum peel force was found with increasing concentration of PEG. Overall, this study demonstrates that the layering process described for the PEG gels has minimal impact on the tested mechanical properties of the system. As mechanical properties are critical to the design of tissue engineered devices, these results demonstrate that this fabrication method may be appropriate for further study as a scaffold for complex cellular systems.

Spray-dried chitosan microspheres cross-linked with d, l-glyceraldehyde as a potential drug delivery system: preparation and characterization

Chitosan microspheres of a small particle size and with good sphericity were prepared by a spray-drying method followed by treatment with a cross-linking agent. Owing to restrictions on the use of cross-linked chitosan microspheres in the pharmaceutical field, d,l-glyceraldehyde, a biocompatible reatant was used. The parameters studied affecting extent of cross-linking were cross-linking time and concentration of the cross-linking agent. Glutaraldehyde, the aldehyde most frequently employed as chemical cross-linking agent for proteins, was also used as a control. The cross-linked spray-dried chitosan microspheres were analyzed with respect to their morphological aspects, particle size, zeta potential and water uptake capacity. It was found that an increase either in d,l-glyceraldehyde concentration or in duration of cross-linking caused a decrease in both the swelling capacity and the zeta potential of the chitosan microspheres. Compared to glutaraldehyde, d,l-glyceraldehyde appears to be a good cross-linking agent for chitosan microspheres with the advantage that it is nontoxic.

Gellan-Based Scleral Implants of Indomethacin: In Vitro and In Vivo Evaluation

Film-type scleral implants of indomethacin with gellan gum were prepared by solvent casting and evaluated for uniformities of thickness, weight, drug content, and surface pH. The effect of plasticizers like glycerol, propylene glycol (PG), and polyethylene glycol 200, and 400 on the void volume of free gellan films (placebo) was calculated from the water content of the films. The drug release from the prepared implants was determined using a static dissolution set-up developed and optimized in our laboratory. Based on the results of the void volume and initial drug release studies, glycerol and PG were selected as the plasticizers for the gellan-based implants. The morphology of the drug-free films (containing 10% and 40% of PG) and the drug-loaded films (before and after dissolution and crosslinked) was studied using scanning electron microscopy. Further, the effect of plasticizer concentration, gellan concentration, effect of crosslinking technique, and duration of crosslinking using calcium chloride on in vitro drug release characteristics were evaluated. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis-induced (intravitreal injection of bovine serum albumin 50 μg/ml) rabbit eyes. The release of indomethacin from the prepared implants followed matrix diffusion kinetics with diffusion co-efficient (n) values ranging between 0.358 to 0.708 and seemed to depend on both gellan and plasticizer concentration. Surface crosslinking with 10% calcium chloride for 8 hr retarded drug release (1.42 times less than noncrosslinked implant) and was optimum. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in the implanted eye compared with the control eye in the rabbits. The scleral implants survived up to 3 weeks in vivo.

Cyclophosphamide loaded albumin microspheres II. Release characteristics

The purpose of this investigation was to evaluate the release characteristics of cyclophosphamide (CP) from glutaraldehyde stabilized human serum albumin microspheres, and to study the effect of the extent of cross-linking, the amount of the stabilizing agent and the size of the microspheres on the in vitro release of CP. Microspheres were prepared by emulsion polymerization method using two different volumes (0.1 and 0.7 ml) of glutaraldehyde solution (25 per cent) and two different crosslinking durations (15 min and 1 h). The resulting mean particle size of the microspheres also varied between 2.5 microns and 3.7 microns. The total CP content in microspheres was analysed from the surface drug and the entrapped drug.