MARVEL ZOE IMMANUELLA FORMULASI DAN KARAKTERISASI NANOSTRUCTURED LIPID CARRIER(NLC) MENGANDUNG SIMVASTATIN SERTA AKTIVITAS SITOTOKSIK TERHADAP TRIPLE NEGATIVE BREAST CANCER(TNBC) PROGRAM STUDI SAINS DAN TEKNOLOGI FARMASI SEKOLAH FARMASI INSTITUT TEKNOLOGI BANDUNG 2024 ABSTRAK dƌŝƉůĞ EĞŐĂƟǀĞ ƌĞĂƐƚ CĂŶĐĞƌ (TNBC)ĂĚĂůĂŚ ƐĂůĂŚ ƐĂƚƵ ũĞŶŝƐ ŬĂŶŬĞƌ ƉĂLJƵĚĂƌĂ LJĂŶŐ ƟĚĂŬ ŵĞŵŝůŝŬŝ reseptorŚŽƌŵŽŶ ĞƐƚƌŽŐĞŶ͕ ƉƌŽŐĞƐƚĞƌŽŶ͕ ĚĂŶ ,ZϮ͘ dEC ĚŝŬĞŶĂů ƐĞďĂŐĂŝ ƐƵďƟƉĞ ŬĂŶŬĞƌ ƉĂLJƵĚĂƌĂ LJĂŶŐ ƉĂůŝŶŐ ĂŐƌĞƐŝĨ ĚĞŶŐĂŶ ĂŶŐŬĂ ŬĞŬĂŵďƵŚĂŶ ƟŶŐŐŝ͕ ĂŶŐŬĂ ŬĞƐĞŵďƵŚĂŶ ƌĞŶĚĂŚ͕ ĚĂŶ ƟŶŐŬĂƚ ŚĂƌĂƉĂŶ ŚŝĚƵƉ ƌĞŶĚĂŚ͘ dŝĚĂŬ ĂĚĂŶLJĂ ŬĞƟŐĂ ƌĞƐĞƉƚŽƌ ŚŽƌŵŽŶ ŵĞŶLJĞďĂďŬĂŶ ƉŝůŝŚĂŶ ƉĞŶŐobatan untuk TNBC menjadi lebih terbatas. Selain itu, telah banyak dilaporkan kasus kemoresistensi pada TNBC akibat pemberian kemoterapi yang merupakan opsi terapi utama TNBC. Untuk itu, diperlukan ƉĞŶŐĞŵďĂŶŐĂŶ ĂůƚĞƌŶĂƟĨ ƚĞƌĂƉŝ ůĂŝŶ LJĂŶŐ ůĞďŝŚ ĞĨĞŬƟĨ͕ ƐĂlah satunya dengan menggunakan konsep drug repurposingyang dikombinasi dengan suatu sistem penghantaran obat. Salah satu kandidat ŽďĂƚ LJĂŶŐ ƉŽƚĞŶƐŝĂů ƵŶƚƵŬ ĚŝŐƵŶĂŬĂŶ ĂĚĂůĂŚ ƐŝŵǀĂƐƚĂƟŶ͕ ŽďĂƚ ĂŶƟŚŝƉĞƌůŝƉŝĚĞŵŝĂ ŐŽůŽŶŐĂŶ ƐƚĂƟŶ͘ WĂĚĂ ƉĞŶĞůŝƟĂŶ ŝŶŝ ĚŝŬĞŵďĂŶŐŬĂŶ ƐŝƐƚĞŵ ƉĞŶŐŚĂŶƚĂƌĂŶ ƐŝŵǀĂƐƚĂƟŶ ;^ŝŵͿ ĚĞŶŐĂŶ Nanostructured Lipid Carrier;E>CͿ ƐĞƌƚĂ ƉĞŶŐƵũŝĂŶ ĂŬƟǀŝƚĂƐ ƐŝƚŽƚŽŬƐŝŬ ƚĞƌŚĂĚĂƉ dEC͘ WĞŶĞůŝƟĂŶ ŝŶŝ ďĞƌƚƵũƵĂŶ ƵŶƚƵŬ ŵĞŶĞŶƚƵŬĂŶ ĨŽƌŵƵůĂ ĚĂŶ ƉƌŽƐĞƐ ƉĞŵďƵĂƚĂŶ ŽƉƟŵĂů E>C-^ŝŵ͕ ŵĞŶŐƵũŝ ŬĂƌĂŬƚĞƌŝƐƟŬ E>C-Sim, menguji stabilitas NLC-^ŝŵ͕ ĚĂŶ ŵĞŶŐƵũŝ ĂŬƟǀŝƚĂƐ ƐŝƚŽƚŽŬƐŝŬ E>C-^ŝŵ͘ WĞŶĞůŝƟĂŶ ĚŝĂǁĂůŝ ĚĞŶŐĂŶ ƉƌŽƐĞƐ ŽƉƟŵĂƐŝ ĨŽƌŵƵůĂ LJĂŶŐ ĚŝŝŬƵƟ ĚĞŶŐĂŶ ŬĂƌĂŬƚĞƌŝƐĂƐŝ ĚĂŶ Ƶũŝ ƐƚĂďŝůŝƚĂƐ E>C-Sim. Formula ŽƉƟŵĂů ŬĞŵƵĚŝĂŶ ĚŝƵũŝ ĂŬƟǀŝƚĂƐ ƐŝƚŽƚŽŬƐŝŬ ƚĞƌŚĂĚĂƉ ƐĞů ϰdϭ LJĂŶŐ merupakan model TNBC. Hasil ŽƉƟŵĂƐŝ ĨŽƌŵƵůĂ ĚŝƉĞƌŽůĞŚ ĨŽƌŵƵůĂ ŽƉƟŵĂů ĚĞŶŐĂŶ ŬŽŵƉŽŶĞŶ ůŝƉŝĚ ƉĂĚĂƚ ĚĂŶ ůŝƉŝĚ ĐĂŝƌ ďĞƌƵƉĂ beeswaxdanvirgin coconut oil(VCO) dengan konsentrasi total 4% dan rasio 3:1. Kombinasi surfaktan yang diperoleh adalah Tween 80 danPEG 400 dengan konsentrasi total 5% dan rasio 4:1. ĞƌĚĂƐĂƌŬĂŶ ŽƉƟŵĂƐŝ ƉƌŽƐĞƐ͕ ĚŝƉĞƌŽůĞŚ ƉƌŽƐĞƐ ƐŽŶŝŬĂƐŝ ŽƉƟŵĂů ďĞƌƵƉĂ ĚƵĂ ƚĂŚĂƉ ƐŽŶŝŬĂƐŝ menggunakansonicator bathdansonicator probe. NLC-^ŝŵ ŽƉƟŵĂů LJĂŶŐ ĚŝĚĂƉĂƚŬĂŶ ŵĞŵŝůŝŬŝ ƵŬƵƌĂŶ ƉĂƌƟŬĞů sebesar 192,10 ± 11,73 nm, indeks polidispersitas sebesar 0,25 ± 0,02, zeta potensial sebesar-8,67 ± 2,41 mV, dan efisiensi enkapsulasi sebesar 99,11 ± 0,25%. NLC-Sim menunjukkan stabilitas yang baik pada penyimpanan di suhu 2-8 °C selama 14 hari. Hasil uji sitotoksik terhadap sel 4T1 menunjukkan bahwa NLC-Sim memberikan efek lebih baik dibandingkan NLC blanko dan ůĂƌƵƚĂŶ ƐŝŵǀĂƐƚĂƟŶ͕ ĚĞŶŐĂŶ ŶŝůĂŝ /C50sebesar 80,84 ± 11,62 µM. Hasil ini menunjukkan bahwa ƉĞŶŐŚĂŶƚĂƌĂŶ ƐŝŵǀĂƐƚĂƟŶ ŵĞŶŐŐƵŶĂŬĂŶ E>C ďĞƌƉŽƚĞŶƐŝƐĞďĂŐĂŝ ĂůƚĞƌŶĂƟĨ ƚĞƌĂƉŝ dEC͘ Kata kunci:dƌŝƉůĞ EĞŐĂƟǀĞ ƌĞĂƐƚ CĂŶĐĞƌ͕ ƐŝŵǀĂƐƚĂƟŶ͕ Nanostructured Lipid Carrier ABSTRACT dƌŝƉůĞEĞŐĂƟǀĞƌĞĂƐƚĂŶĐĞƌ;dEͿŝƐĂƚLJƉĞŽĨďƌĞĂƐƚĐĂŶĐĞƌƚŚĂƚĚŽĞƐŶ͛ƚŚĂǀĞƚŚĞŚŽƌŵŽŶĞ receptors estrogen, progesterone, and HER2. TNBC is known as the most aggressive subtype of breast cancer with a high recurrence rate, low cure rate, and low survival rate. Having absent of all ƚŚƌĞĞŚŽƌŵŽŶĞƌĞĐĞƉƚŽƌƐŵĞĂŶƐƚŚĞƌĂƉLJŽƉƟŽŶƐĨŽƌdEĂƌĞŵŽƌĞůŝŵŝƚĞĚ͘/ŶĂĚĚŝƟŽŶ͕ŵĂŶLJĐĂƐĞƐ of chemoresistance in TNBC have been reported due to chemotherapy, which is the main therapy ŽƉƟŽŶĨŽƌdE͘&ŽƌƚŚŝƐƌĞĂƐŽŶ͕ŝƚŝƐŶĞĐĞƐƐĂƌLJƚŽĚĞǀĞůŽƉĂůƚĞƌŶĂƟǀĞƚŚĞƌĂƉŝĞƐƚŚĂƚĂƌĞŵŽƌĞ ĞīĞĐƟǀĞ͕ŽŶĞŽĨǁŚŝĐŚŝƐƵƐŝŶŐƚŚĞĐŽŶĐĞƉƚŽĨĚƌƵŐƌĞƉƵƌƉŽƐŝŶŐĐŽŵďŝŶĞĚǁŝƚŚĂĚƌƵŐĚĞůŝǀĞƌLJ ƐLJƐƚĞŵ͘KŶĞƉŽƚĞŶƟĂůĚƌƵŐĐĂŶĚŝĚĂƚĞŝƐƐŝŵǀĂƐƚĂƟŶ͕ĂƐƚĂƟŶĂŶƟ-hyperlipidemia drug. In this reƐĞĂƌĐŚ͕ĂƐŝŵǀĂƐƚĂƟŶ;^ŝŵͿĚĞůŝǀĞƌLJƐLJƐƚĞŵƵƐŝŶŐEĂŶŽƐƚƌƵĐƚƵƌĞĚ>ŝƉŝĚĂƌƌŝĞƌ;E>ͿŚĂƐďĞĞŶ ĚĞǀĞůŽƉĞĚĂŶĚĐLJƚŽƚŽdžŝĐĂĐƟǀŝƚLJĂŐĂŝŶƐƚdEŚĂƐďĞĞŶƚĞƐƚĞĚ͘dŚĞƌĞƐĞĂƌĐŚĂŝŵĞĚƚŽĚĞƚĞƌŵŝŶĞ ƚŚĞŽƉƟŵĂůĨŽƌŵƵůĂĂŶĚŵĂŶƵĨĂĐƚƵƌŝŶŐƉƌŽĐĞƐƐĨŽƌE>-Sim, test theĐŚĂƌĂĐƚĞƌŝƐƟĐƐŽĨE>-Sim, test the stability of NLC-^ŝŵ͕ĂŶĚƚĞƐƚƚŚĞĐLJƚŽƚŽdžŝĐĂĐƟǀŝƚLJŽĨE>-Sim. The research began with a ĨŽƌŵƵůĂŽƉƟŵŝnjĂƟŽŶƉƌŽĐĞƐƐĨŽůůŽǁĞĚďLJĐŚĂƌĂĐƚĞƌŝnjĂƟŽŶĂŶĚƐƚĂďŝůŝƚLJƚĞƐƟŶŐŽĨE>-Sim. The ŽƉƟŵĂůĨŽƌŵƵůĂǁĂƐƚŚĞŶƚĞƐƚĞĚĨŽƌĐLJƚŽƚŽdžŝĐĂĐƟǀŝƚLJĂŐĂŝŶƐƚϰdϭĐĞůůƐǁŚŝĐŚĂƌĞŵŽĚĞůŽĨdE͘ dŚĞƌĞƐƵůƚƐŽĨĨŽƌŵƵůĂŽƉƟŵŝnjĂƟŽŶŚĂǀĞŽďƚĂŝŶĞĚĂŶŽƉƟŵĂůĨŽƌŵƵůĂǁŝƚŚďĞĞƐǁĂdžĂŶĚǀŝƌŐŝŶ ĐŽĐŽŶƵƚŽŝů;sKͿĂƐƐŽůŝĚůŝƉŝĚĂŶĚůŝƋƵŝĚůŝƉŝĚĐŽŵƉŽŶĞŶƚƐǁŝƚŚĂƚŽƚĂůĐŽŶĐĞŶƚƌĂƟŽŶŽĨϰйĂnd a ƌĂƟŽŽĨϯ͗ϭ͘dŚĞƐƵƌĨĂĐƚĂŶƚĐŽŵďŝŶĂƟŽŶŚĂƐďĞĞŶŽďƚĂŝŶĞĚǁĂƐdǁĞĞŶϴϬĂŶĚW'ϰϬϬǁŝƚŚĂƚŽƚĂů ĐŽŶĐĞŶƚƌĂƟŽŶŽĨϱйĂŶĚĂƌĂƟŽŽĨϰ͗ϭ͘ĂƐĞĚŽŶƉƌŽĐĞƐƐŽƉƟŵŝnjĂƟŽŶ͕ĂŶŽƉƟŵĂůƐŽŶŝĐĂƟŽŶƉƌŽĐĞƐƐ ŚĂƐďĞĞŶŽďƚĂŝŶĞĚǁŚŝĐŚŝƐĂĐŽŵďŝŶĂƟŽŶŽĨƚǁŽƐŽŶŝĐĂƟŽŶƐƚĂŐĞƐƵƐŝŶŐďĂƚŚƐŽŶŝĐĂƚŽƌĂŶĚƉƌŽďĞ ƐŽŶŝĐĂƚŽƌ͘dŚĞŽƉƟŵĂůE>-^ŝŵŚĂĚĂƉĂƌƟĐůĞƐŝnjĞŽĨϭϵϮ͘ϭϬцϭϭ͘ϳϯŶŵ͕ĂƉŽůLJĚŝƐƉĞƌƐŝƚLJŝŶĚĞdžŽĨ Ϭ͘ϮϱцϬ͘ϬϮ͕ĂnjĞƚĂƉŽƚĞŶƟĂůŽĨ-ϴ͘ϲϳцϮ͘ϰϭŵs͕ĂŶĚĂŶĞŶĐĂƉƐƵůĂƟŽŶĞĸĐŝĞŶĐLJŽĨϵϵ͘ϭϭцϬ͘Ϯϱй͘ NLC-Sim has shown adequate stability when stored at 2-8 °C for 14 days. The results of the cytotoxic test on 4T1 cells showed that NLC-^ŝŵŚĂĚĂďĞƩĞƌĞīĞĐƚƚŚĂŶE>ďůĂŶŬĂŶĚƐŝŵǀĂƐƚĂƟŶƐŽůƵƟŽŶ͕ with an IC50ǀĂůƵĞŽĨϴϬ͘ϴϰцϭϭ͘ϲϮђD͘dŚĞƐĞƌĞƐƵůƚƐŚĂǀĞŝŶĚŝĐĂƚĞĚƚŚĂƚƐŝŵǀĂƐƚĂƟŶĚĞůŝǀĞƌLJƐLJƐƚĞŵ ƵƐŝŶŐE>ŚĂĚƉŽƚĞŶƟĂůĂƐĂŶĂůƚĞƌŶĂƟǀĞƚŚĞƌĂƉLJĨŽƌdE͘ Keywords:TripleEĞŐĂƟǀĞƌĞĂƐƚĂŶĐĞƌ͕ƐŝŵǀĂƐƚĂƟŶ͕Nanostructured Lipid Carrier.