Local pharmaceutical release from a new hydrogel implant.
BACKGROUND
Solid hydrogel polymers can act as reservoirs for controlled drug release. The object of this study was to quantify release kinetics for a single example of a class of uniquely structured hydrogels. The polymer of this study belongs to a class of permanent implants that release pharmaceuticals by diffusion from an entangled cross-linked matrix rather than by absorption of the implant by the body. The cross-linked matrix (CLM) of this study is biocompatible and polymerized in situ, forming a solid that is mechanically bonded to the implant site. It can seal tissue as well as deliver drugs at predetermined rates. We evaluated dye and antibiotic egress and assessed release kinetics and retention of antibiotic activity following elution from the CLM.


METHODS
The prepolymerized test CLM was prepared in two ratios, 6 and 20% prepolymer, in an activating aqueous solution. Aqueous solutions were prepared from dyes of varying molecular weights. Aliquots of prepolymerized test CLM were allowed to solidify and dye release into the supernatant was quantified by spectrophotometry over a 168-h period. Antibiotic solutions were also employed to form solid CLMs. Tetracycline release over time was characterized by spectrophotometry. Antibiotic dosed solid CLMs were placed on agar plates streaked with Escherichia coli and incubated. Growth inhibition was assessed for each antibiotic.


RESULTS
In the test CLM, dye and antibiotic release were found to be inversely related to molecular weight and consistent with a diffusion model. CLMs formed from aqueous solutions containing higher molecular weight dyes and antibiotics released those constituents more slowly than lower molecular weight constituents. This finding, as well as the effect on release rate under varying prepolymer concentration, was consistent with a diffusion release mechanism. Antibiotic released from the tissue sealant was shown to be potent by consistent inhibition of E. coli.


CONCLUSIONS
Pharmaceutical release by a representative CLM was found to be controllable by varying the concentration of the pharmaceutical in the activating aqueous solution. The polymerization and release mechanisms did not degrade antibiotic biologic activity. CLMs may be a general class of biocompatible polymers that can locally deliver clinically useful biologics, the release kinetics of which are unaffected by the variability of implant absorption/inflammation mechanisms.
Petratos
Peter B
PB
Center for Pediatric Urology and Laboratory for Minimal Invasive Urologic Surgery, Weill Medical College of Cornell University, New York, New York 10021, USA.
Chen
Jie
J
Felsen
Diane
D
Poppas
Dix P
DP
D004396:Coloring Agents / Q000737:chemistry / Q000493:pharmacokinetics; D003432:Cross-Linking Reagents / Q000737:chemistry; D004058:Diffusion; D004926:Escherichia coli; D005840:Gentian Violet / Q000737:chemistry / Q000493:pharmacokinetics; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D015918:Infusion Pumps, Implantable; D008751:Methylene Blue / Q000737:chemistry / Q000493:pharmacokinetics; D008970:Molecular Weight; D012394:Rosaniline Dyes / Q000737:chemistry / Q000493:pharmacokinetics; D013752:Tetracycline / Q000493:pharmacokinetics*; D013754:Tetracyclines / Q000493:pharmacokinetics*
D004396:Coloring Agents; D003432:Cross-Linking Reagents; D012394:Rosaniline Dyes; D013754:Tetracyclines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C035906:Fast Green; D013752:Tetracycline; D005840:Gentian Violet; D008751:Methylene Blue