FOTOPROTEKSI SINAR ULTRAVIOLET B SEDIAAN NANOEMULGEL KOMBINASI C-METILKALIKS[4]RESORSINARIL OKTABENZOAT, C-FENILKALIKS[4] RESORSINARIL OKTASINAMAT, DAN QUERCETINE SECARA IN VITRO DAN IN VIVO (Kajian Formulasi, Aktivitas, dan Mekanisme Aksi Formulasi)

AGUNG WIWIEK INDRAYANI, Prof. Dr. Mustofa, M.Kes, Apt .; Dr. dr. Sunardi Radiono, Sp.KK.; Prof. Dr. Suwaldi Martodihardjo, MSc, Apt .;

2018 | Disertasi | DOKTOR ILMU KEDOKTERAN DAN KESEHATAN

Senyawa tabir surya organik yang efektif dan aman digunakan oleh masyarakat luas sangat diperlukan. Dua senyawa tabir surya organik yaitu C- fenilkalik[4]resorsinaril oktasinamat dan C-metilkalik[4]resorsinaril oktabenzoat berhasil disintesis. Penggunaan kedua senyawa ini akan dikombinasikan dengan antioksidan quercetine untuk meredam radikal bebas. Ketiga bahan tabir surya memiliki kelarutan yang rendah dalam air, pendekatan teknologi nano digunakan untuk memformulasikan tabir surya kombinasi membentuk nanoemulgel tabir surya. Penelitian ini bertujuan mengkaji formulasi optimal, aktifitas sediaan, mekanisme aksi serta toksisitas akut sediaan. Formulasi optimal dari tiga bahan tabir surya didapatkan dengan menggunakan desain penelitian yaitu D Optimal Mixture Design. Aktivitas sediaan dengan mengukur nilai SPF in vivo dan jumlah sel mast pada kulit kelinci albino galur New Zealand menggunakan desain penelitian randomized post-test only control group design. Mekanisme aksi sediaan dengan mengukur ekspresi histopatologi katalase, COX-2 dan MMP-1, serta kadar IL-1 dengan ELISA pada kulit kelinci albino galur New Zealand menggunakan desain penelitian randomized post-test only group design. Toksisitas in vitro pada kultur sel vero menggunakan desain penelitian randomized post-test only group design. Analisis data uji formulasi menggunakan Design Expert 7.1.5, aktivitas sediaan (nilai SPF in vivo dan jumlah sel mast) dianalisis menggunakan Anova satu jalur, mekanisme aksi sediaan (ekspresi katalase, COX-2, MMP-1) dianalis dengan menggunakan Kruskal Wallis, kadar IL- 1beta dianalisis dengan menggunakan Anova satu jalur serta toksisitas akut in vitro dianalisis dengan menggunakan probit. Tiga formula tabir surya nanoemulgel dihasilkan dengan tiga SPF tertinggi. Hasil optimasi memperlihatkan optimum formula satu, dua dan tiga secara berurutan memiliki nilai SPF in vitro 104,9; 121,3; 81,6 nilai transmittance 99,93; 97,59; 90,84 %, waktu emulsifikasi 22,01; 18,35; 17,42 detik. Nilai z average sebesar 57,3; 76,5; 88,4 nm. Uji SPF in vivo memperlihatkan kemampuan proteksi nanoemulgel formula satu pada dosis 1 ; 2; dan 4 mg/cm2 berturut turut adalah 34; 36; dan 43. Mekanisme kerja sediaan tabir surya melalui jalur IL1beta, katalase, MMP-1(p<0,05), COX-2 (p>0,05) dan nilai IC50 sitotoksisitas pada sel vero masing masing formula 1, 2, 3 nanoemulgel berturut turut adalah 2.940,569 mcg/mL; 13.489,728 mcg/mL; 6.289.248 mcg/mL. Dari penelitian ini disimpulkan bahwa tiga produk tabir surya nanoemulgel berhasil diformulasikan dengan kandungan SPF in vivo tinggi dan potensial dikembangkan sebagai tabir surya organik di masa depan.

Organic and inorganic sunscreen products are comercially available. Two calixarene organic compounds, namely C-phenylcalix[4]resorcinaryl octacinnamate and C-methylcalix[4]resorcinaryl octabenzoate, had been successfully synthesized. The antioxidant quercetine can be potentially combined with these two compounds because ultraviolet rays also cause reactive oxygen species that can be overcomed by the administration of antioxidant. These three compounds have low solubility in water, thus sunscreen preparation must be formulated as nanoemulgel. The aim of this study was to develop optimal nanoemulgel formulation, activity of the product, mechanism of action and acute toxicity profile. Optimal formulation from three compounds of sunscreen was used D Optimal Mixture Design. Activity of the product by measuring the value of SPF in vivo and the number of sel mast on the albino rabbit skin of the New Zealand strain using randomized post-test only control group design. Mechanism of action by measuring the expression of histopathological of catalase, COX-2, MMP-1, and value of IL-1 by ELISA on the albino rabbit skin of the New Zealand strain using randomized post-test only control group design. Acute cytotoxicity test in vitro by culture cell line vero was used randomized post-test only control group design. Analysis of formulation was using Design Expert 7.1.5. Activity bioassays (in vivo SPF, mast cell ) were analysed using one-way Anova, in vivo molecular mechanism action (catalase enzyme, COX-2, MMP-1, IL-1) were analysed using Kruskal Wallis. Data IL-1beta were analysed using one way Anova. Data of acute toxicity in vitro test ( IC50 value) was analysed using probit analysis. Three nanoemulgel sunscreen products were produced with the three highest SPF values. The optimum results showed that formula 1, 2, 3 had SPF value in vitro 104.9; 121.3; 81.6 respectively, transmittance value 99.93; 97.59; 81.56 % respectively, emulsification time 22.01, 18.35, 17.42 seconds, z average 57.3, 76.5, 88.4 nm. SPF in vivo test showed that the nanoemulgel protection capability of the formula 1. 2, and 3 were 34; 36; dan 43 respectively. Mechanism action of nanoemulgel sunscreen were predicted by IL1-beta, Catalase (p<0,05) and COX-2 (p>0,05). The results of in vitro toxicity test of formula 1, 2, 3 nanoemulgel were 2,940.569 mcg/mL; 13,489.728 mcg/mL; 6,289.248 mcg/mL respectively. From this study, it was concluded that nanoemulgel sunscreen products were successfully formulated with high in vivo SPF value and can be potentially developed as organic suncreens in the future.

Kata Kunci : C-fenilkalikresorsinaril oktasinamat, C-metilkalik[4]resorsinaril oktabenzoat, quercetine, formulasi, aktivitas sediaan, mekanisme aksi, C-phenylcalix[4]resorcinaryl octacinnamate, C-methylcalix[4]resorcinaryl octabenzoate, formulation, activity bioass