Desain Controlled Release Drug-Eluting Stent dengan Multi-Lapisan Kitosan dan Kurkumin

Jeremia Frandy Apitalau, drg. Heribertus Dedy Kusuma Yulianto, M.Biotech., Ph.D; dr. Dyah Listyarifah, M.Sc., D.Med.Sci

2025 | Tesis | MAGISTER TEKNIK BIOMEDIS

Dalam praktik klinis, beberapa produk komersial drug-eluting stent komersial memiliki keterbatasan pada fase awal pelepasan obat, karena menyebabkan initial burst release. Hal ini dapat menyebabkan peningkatan risiko restenosis. Untuk memenuhi keterbatasan tersebut, penelitian ini dirancang dengan menggunakan strategi multi lapisan dengan kitosan terikat silang genipin sebagai polimer dan kurkumin sebagai obat yang diukur. Berdasarkan forward speed dari rotary drive (7, 8 dan 9 mm/s), ultrasonic coating digunakan untuk membuat lapisan yang homogen. Validitas metode spektrofotometri UV-Vis dikonfirmasi oleh uji validasi. Ketebalan multi lapisan berbeda secara signifikan di antara forward speed, sedangkan pelepasan kurkumin tidak signifikan. Permukaan multi lapisan ditemukan berbeda pada 9 mm/s. Dalam pemodelan data pelepasan, profil rilis menunjukkan kecocokan yang dekat dengan model Korsmeyer-Peppas, menunjukkan mekanisme transpor super case II dengan mekanisme pelepasan relaksasi/erosi. Berdasarkan model Peppas-Sahlin, mekanisme pelepasan didominasi oleh Fickian diffusion dalam 6-7 hari pertama. Kemudian,  menurun secara bertahap sampai relaksasi polimer menjadi dominan di akhir. Profil kontribusi difusi fickian berbeda pada kelompok C (9 mm/s) yang dapat bertahan sampai 7 hari pertama, dibandingkan pada kelompok A (7 mm/s) dan B (8  mm/s), mekanisme difusi yang bertahan sampai 6 hari pertama. Sistem yang didesain dapat memberikan integritas matriks yang cukup kuat di awal pelepasan, Sehingga dapat mencegah initial burst release. Setelah terjadi perubahan mekanisme pelepasan dari difusi ke relaksasi, profil pelepasan tidak menunjukan terjadinya burst release. Adapun, kecocokan dalam model zero-order menginterpretasikan desain telah memenuhi profil pelepasan yang terkendali tanpa adanya initial burst release.

In clinical practice, several commercial drug-eluting stent products exhibit limitations in the early drug release phase, as they cause initial burst release. Ultimately, this may lead to an increased risk of restenosis. This experimental study used a multilayer strategy of genipin-crosslinked chitosan as the polymer and curcumin as the measured drug to fulfil the limitation. Based on the forward speed of the rotary drive (7, 8 and 9 mm/s), ultrasonic coating is utilized to create a homogeneous layer. The validation test confirmed the validity of the UV-Vis spectrophotometric method. Measured by SEM, the thickness of the multilayers differed significantly between forward speeds while the release of curcumin was insignificant. The multilayer surface was found to be different at 9 mm/s. In modelling the release data, the release profile showed a close fit to the Korsmeyer-Peppas model shows a super case II transport mechanism with a relaxation/erosion release mechanism. Based on the Peppas-Sahlin model and showed that the Fickian diffusion contribution dominated the first 6-7 days, then gradually decreased until polymer relaxation became dominant at the end. The contribution profile of Fickian diffusion was different in C (9  mm/s) which extends for a period of up to seven days, compared to A (7 mm/s) and B (8 mm/s), the Fickian diffusion mechanism persisted only until the first six days. Overall, the designed multilayer system is capable of ensuring sufficient matrix integrity at the initial phase of release, Therefore, the prevention of initial burst release is achieved. In contrast, following the transition of the release mechanism from diffusion to relaxation, the burst release is unobserved. Additionally, the goodness of fit in the zero-order model reflected the design as fulfilling the controlled release profile without initial burst release.

Kata Kunci : drug-eluting stent, multilayer, controlled release, ultrasonic coating