FORMULASI SNEDDS MINYAK ATSIRI RIMPANG Curcuma mangga Val. DAN UJI KEMOPREVENTIF KANKER PAYUDARA PADA TIKUS YANG DIINDUKSI 7,12-DIMETILBENZ[A]ANTRASEN (DMBA)

LUKMAN MAHDI, Prof. Dr. apt. Retno Sunarminingsih, M.Sc.; drh. Retno Murwanti, M.P., Ph.D.

2021 | Tesis | MAGISTER ILMU FARMASI

Minyak atsiri rimpang Curcuma mangga Val. diketahui memiliki efek sitotoksik pada sel kanker payudara baik secara in vitro maupun in silico; sehingga minyak atsiri tersebut berpotensi dikembangkan sebagai agen antikanker. Namun minyak atsiri tersebut tidak larut air, mudah menguap, serta tidak stabil dalam penyimpanan dan dosis pemberian; sehingga mengurangi efektifitasnya sebagai sediaan antikanker. Oleh karena itu, minyak atsiri C. mangga Val. perlu dibuat nanoemulsi. Tujuan penelitian ini untuk mendapatkan formula optimum SNEDDS minyak atsiri C. mangga Val., mengetahui stabilitasnya dan mengevaluasi efek antikankernya pada tikus yang diinduksi DMBA. Formulasi nanoemulsi minyak atsiri C. mangga Val. dilakukan dengan teknik self nanoemulsifying drug delivery system (SNEDDS) dengan komponen migliol, Tween 80 dan PEG 400; serta dioptimasi dengan Design Expert Ver. 10 dengan metode simplex lattice design (SLD). Respon yang diuji adalah transmitan dan waktu emulsifikasi pada media akuades, artificial gastric fluide (AGF) dan artificial intestine fluide (AIF). Formula optimum kemudian dikarakterisasi, diuji stabilitasnya dan diujikan pada tikus yang diinduksi DMBA. Uji in vivo kemopreventif dilakukan dengan pemberian minyak atsiri, nanoemulsinya dan tamoksifen (kontrol positif) sebelum dan selama perlakuan DMBA. Uji kemopreventif dilakukan selama 14 minggu dengan pengamatan terjadinya nodul pada organ mamae, kemudian diakhiri dengan nekropsi tikus dan dievaluasi histopatologi organ mamaenya. Formula SNEDDS optimum yang diperoleh adalah kombinasi dari Migliol (16.034%), Tween 80 (68.380%) dan PEG 400 (15.586%). Karakteristik nanoemulsi minyak atsiri C. mangga Val. memiliki ukuran tetesan 15.75 nm, potensial zeta -8.54 mV, dan nilai PDI 0.188; serta stabil dalam tiga tes pengujian termodinamik. Hasil uji in vivo menunjukkan bahwa minyak atsiri C. mangga Val. berpotensi kemopreventif antikanker payudara. Sedangkan SNEDDS minyak atsiri C. mangga Val. belum terbukti memiliki potensi antikanker lebih baik daripada minyak atsiri C. mangga Val.

Essential oil of Curcuma mangga Val. rhizome has been proven to have cytotoxic effects on breast cancer cell lines by in vitro and in silico studies, so that it is possible to become anticancer agent. However the oil is water insoluble, very volatile, and unstable in room temperature as well as in administration dose, which cause reduce its effectiveness as an anticancer agent. Therefore the oil needs to prepare in a nanoemulsion. The aim of this study was to obtain the optimal SNEDDS formula, to find out the SNEDDS stability and to evaluate the anticancer effects in DMBA-induced rats. The nanoemulsion formulation of the essential oil of C. mangga Val. was carried out using self nanoemulsifying drug delivery systems (SNEDDS) technique which contains migliol, Tween 80 and PEG 400; which was then optimized the formula using simplex lattice design (SLD) method by Design Expert Ver. 10. The response studies were the transmittance as well as emulsification times in distilled water, artificial gastric fluide (AGF) and artificial intestine fluide (AIF). The optimal SNEDDS formula was then characterized, evaluated its stabilities, and given to DMBA-induced rats. A chemopreventive study was carried out on DMBA-induced rats which given (before and during DMBA initiation) the oil, the oil�s SNEDDS, and tamoxifen as positive control. Rats were necropsied after 14 week study, and the mammary organs were histopathological evaluated. The optimum SNEDDS formula resulted was a combination of migliol (16,034%), Tween 80 (68,380%), and PEG 400 (15,586%). The nanoemulsion characteristics were 15.75 nm droplet size, -8.54 mV zeta potential, and 0.188 PDI as well as being stable in thermodynamic tests. The in vivo study showed that the essential oil potentially being a chemopreventive breast cancer agent. However, the oil�s SNEDDS has not been proven yet to have a better anticancer-potency than the oil.

Kata Kunci : Curcuma mangga Val., minyak atsiri, SNEDDS, DMBA