Pemanfaatan Nanoteknologi dalam Penghantaran Metformin: Kajian Formasi Fibrosis Hati Tikus Model Diabetes
Authors: Pakaya David , Patandung Jusrioktaviani , Anwar Sarifuddin , Ratih Lintin Gabriella Bamba , Fitriana Yuli , Amining Fauziah , Salman Mohammad 
Published: December 2022

ABSTRACT
Metformin is a first-line diabetes therapy but has one of the side effects which is a non-alcoholic fatty liver disease (NAFLD) that triggers the occurrence of fibrosis in the liver. Metformin nanoparticles can improve bioavailability and may reduce side effects. This study aims to analyze the effectiveness of metformin nanoparticle delivery through fasting blood glucose (FGB) levels and liver fibrosis in the diabetic rat model. This is experimental research with a post-test-only controlled group design. This study used 16 white male Wistar rats, 8 weeks of age, body weight (BW) 250-350 g. The streptozotocin (STZ) 40 mg/kg BW were injected i.p. Rats were divided into 4 groups; K1: normal control; K2: negative control (diabetes model); K3: diabetes model treated with metformin 100mg/kg BW; K4: diabetes model treated with nanoparticle metformin 100mg/kg BW. The BW and fasting blood glucose levels were conducted periodically. The histology of fibrosis was performed from Sirius Red staining of liver tissue and quantified using ImageJ software. The data were analyzed with GraphPhad Prism 8.0.0 using the non-parametric Kruskal-Wallis test. Metformin therapy decrease FBG levels on K3 starting on day 21 and K4 starting on day 7, but there was no statistical difference (p=0.0597). The areas of fibrosis were reduced (p=0.002). Metformin nanoparticles were able to decrease FBG levels and effectively reduce the formation of liver fibrosis in the diabetic rat model.

Keywords: diabetes, fibrosis, metformin, nanoparticles

ABSTRAK
Metformin merupakan terapi lini pertama diabetes, namun memiliki efek samping yaitu non-alcoholic fatty liver disease (NAFLD) yang memicu terjadinya fibrosis pada hati. Sediaan nanopartikel metformin dapat meningkatkan bioavailabilitas dan dapat mengurangi efek sampingnya. Tujuan penelitian ini untuk menganalisis efektivitas penghantaran sediaan nanopartikel metformin terhadap kadar glukosa darah puasa (GDP) dan fibrosis hati pada tikus model diabetes. Penelitian ini merupakan eksperimental dengan post-test only controlled group design. Penelitian ini menggunakan 16 ekor tikus putih galur Wistar jantan, berusia 8 minggu, berat badan (BB) 250-350 g. Tikus diinjeksikan streptozotocin (STZ) dosis 40 mg/kg BB. Tikus dibagi dalam 4 kelompok perlakuan; K1: kontrol normal; K2: kontrol negatif (model diabetes); K3: model diabetes + terapi metformin 100mg/kgBB; K4: model diabetes + terapi sediaan nanopartikel metformin 100mg/kg BB. Pengukuran BB dan GDP secara berkala. Area fibrosis didapatkan dari pewarnaan Sirius Red jaringan hati tikus, dan dikuantifikasi menggunakan perangkat lunak ImageJ. Data dianalisis dengan GrapPhad Prism 8.0.0 menggunakan uji non parametrik Kruskal-Wallis. Hasil penelitian ini menunjukkan terapi metformin menurunkan kadar GDP pada K3 mulai pada hari ke-21 dan K4 mulai hari ke-7, namun tidak berbeda secara statistik (p=0,0597). Luas area fibrosis mengecil (p=0,002). Kesimpulan penelitian ini sediaan nanopartikel metformin mampu menurunkan kadar GDP dan efektif mengurangi terbentuknya fibrosis hati pada tikus model diabetes.

Kata kunci: diabetes, fibrosis, metformin, nanopartikel