Chemical modification of polymeric implant surfaces for local drug delivery

摘要

To enhance the biocompatibility of biodegradable biomaterials which are used as implant material surface odifications were performed. Additionally surface modification was used as an alternative drug reservoir to influence specific biological responses to the implants. To realize bonding of an anti-inflammatory model drug to polymer surfaces, chemical modification of different biodegradable polyesters was carried out in comparison to polyurethane (PUR) as reference, which is used as permanent material for implants. For wet chemical surface modification surface degradation reaction of the polyesters poly(L-lactide) (PLLA) and poly(3-hydroxybutyrate) (P(3HB)) was performed under basic conditions to increase the number of reactive hyroxyl and carboxyl groups. Afterwards, 4,4'-methylenebis(phenyl isocyanate) was used to create a terminal isocyanate group. Finally, the isocyanate groups were converted into amino groups. The success of each modification step was confirmed by FTIR-ATR-spectroscopy and measurements of the contact angle with water. Additionally, the detection of amino groups was carried out by fluorescence measurements after reaction of the amino functionalized surfaces with 4-chloro-7-nitrobenzo-2-oxa-l,3-diazole (NBD-Cl) Vcetylsalicylic acid (ASS) was ionically bound to the amino groups of the modified surfaces, and the drug release was analy/ed by HPLC. The release profiles of ASS from PUR showed a steeply increasing release of ASS within 24 hours. In contradt after an initial peak, the release of ASS from P(3HB) und PLLA is nearly constant for more than 17 days (P(3HB)), or rather 42 days (PLLA). The biocompatibility of modified surfaces was measured by the viability of mouse fibroblasts (L929) in direct contact. Only in case of PUR loaded with ASS a decreasing biocompatibility was observed. The presented wet chemical modification of P(3HB) and PLLA turned out to be a promising method to modify these biodegradable polymers for their use as drug releasing implant materials.