Background: Local slow release implant provided long term and stable drug release\nin the lesion. The objective of this study was to fabricate biodegradable slow release\nINH/PLLA tablet via 3 dimensional printing technique (3DP) and to compare the\ndrug release characteristics of three different structured tablets in vitro.\nMethods: Three different drug delivery systems (columnar-shaped tablet (CST),\ndoughnut-shaped tablet (DST) and multilayer doughnut-shaped tablet (MDST)) were\nmanufactured by the three dimensional printing machine and isoniazid was loaded\ninto the implant. Dynamic soaking method was used to study the drug release\ncharacteristics of the three implants. MTT cytotoxicity test and direct contact test\nwere utilized to study the biocompatibility of the implant. The microstructures of the\nimplantsââ?¬â?¢ surfaces were observed with electron microscope.\nResults: The PLLA powder in the tablet could be excellently combined through 3DP\nwithout disintegration. Electron microscope observations showed that INH\ndistributed evenly on the surface of the tablet in a ââ?¬Å?nest-shapedââ?¬Â way, while the\nsurface of the barrier layer in the multilayer doughnut shaped tablet was compact\nand did not contain INH. The concentration of INH in all of the three tablets were\nstill higher than the effective bacteriostasis concentration (Isoniazid: 0.025 ~ 0.05 ?g/\nml) after 30 dayââ?¬â?¢s release in vitro. All of the tablets showed initial burst release of the\nINH in the early period. Drug concentration of MDST became stable and had little\nfluctuation starting from the 6th day of the release. Drug concentration of DST and\nCST decreased gradually and the rate of decrease in concentration was faster in DST\nthan CST. MTT cytotoxicity test and direct contact test indicated that the INH-PLLA\ntablet had low cytotoxicity and favorable biocompatibility.\nConclusions: Three dimensional printing technique was a reliable technique to\nfabricate complicated implants. Drug release pattern in MDST was the most stable\namong the three implants. It was an ideal drug delivery system for the antibiotics.\nBiocompatibility tests demonstrated that the INH-PLLA implant did not have\ncytotoxicity. The multilayer donut-shaped tablet provided a new constant slow\nrelease method after an initial burst for the topical application of the antibiotic.
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