Abstrak Infeksi Staphylococcus aureus masih menjadi masalah kesehatan akibat peningkatan resistensi antibiotik, termasuk doxycycline. Kombinasi antibiotik dengan bahan alami berbasis nanopartikel diperkirakan dapat meningkatkan efektivitas terapi. Studi ini bertujuan untuk menentukan efektivitas kombinasi nanopartikel kitosan – ekstrak daun mangga Arumanis (Mangifera indica L.) dan doxycycline dalam menghambat Staphylococcus aureus serta mengevaluasi aktivitas antibakteri pada beberapa konsentrasi. Metode eksperimen laboratorium in vitro dilakukan dengan maserasi ekstrak etanol 70%, formulasi nanopartikel kitosa, dan karakterisasi Scanning Electron Microscopy (SEM). Uji difusi cakram menggunakan kombinasi nanopartikel 2,5%, 5%, dan 7,5% dengan 30 μg doksisiklin. Hasilnya menunjukkan hasil ekstrak sebesar 23,84% dan ukuran nanopartikel rata-rata 114,5 nm. Diameter zona hambatan rata-rata berturut-turut adalah 24,70, 27,56, dan 30,58 mm untuk formulasi 2,5%, 5%, dan 7,5%, masing-masing. Tes Kruskal–Wallis menunjukkan perbedaan signifikan antar kelompok (p=0,009). Konsentrasi sebesar 7,5% menghasilkan zona hambatan terbesar. Disimpulkan bahwa kombinasi ekstrak daun mangga chitosan–Arumanis dan nanopartikel doxycycline secara efektif menghambat Staphylococcus aureus, dengan konsentrasi 7,5% dan 30 μg doxycycline menunjukkan aktivitas tertinggi. Penelitian lebih lanjut direkomendasikan untuk uji MIC, MBC, sinergisme, toksisitas, dan in vivo guna mendukung pengembangan formulasi terapi pendamping antibiotik. Kata kunci: daun mangga arumanis; nanopartikel kitosan; doksisiklin; Staphylococcus aureus; antibakteri Abstract Staphylococcus aureus infection remains a health issue due to rising antibiotic resistance, including doxycycline. Combining antibiotics with natural nanoparticle-based agents is expected to enhance therapeutic efficacy. This study aimed to examine the effectiveness of a combination of chitosan nanoparticles, Arumanis mango (Mangifera indica L.) leaf extract, and doxycycline in inhibiting Staphylococcus aureus, and to evaluate antibacterial activity at various concentrations. An in vitro experiment utilized 70% maceration for leaf extraction, chitosan nanoparticle formulation, and characterization using Scanning Electron Microscopy (SEM) and disk diffusion assays with nanoparticle-doxycycline combinations at 2,5%,5% and 7,5%. The results showed an extraction yield of 23.84% and an average nanoparticle size of 114.5 nm. The mean inhibition zone diameters were 24.70 mm, 27.56 mm, and 30.58 mm for the 2.5%, 5%, and 7.5% formulations, respectively. The Kruskal–Wallis test indicated significant differences between groups (p=0.009). The 7.5% concentration produced the largest inhibition zone. It is concluded that the combination of chitosan–Arumanis mango leaf extract nanoparticles and doxycycline effectively inhibits Staphylococcus aureus, with the 7.5% concentration and 30 μg doxycycline exhibiting the highest activity. Further investigations on MIC, MBC, synergism effect, toxicity, and in vivo assays are warranted to advanced antibiotic-adjuvant therapeutic formulation development. Keywords: arumanis mango leaf; chitosan nanoparticles; doxycycline; Staphylococcus aureus; antibacterial
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