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"Ruang lingkup dan cara penelitian: Glukokortikoid memiliki efek penting terhadap proses seluler dan metabolik yang berperan dalam respon imun dan inflamasi. Masalah utama dalam penggunaan glukokortikoid adalah dalam timbulnya efek samping yang sering terjadi pada pemberian jangka panjang dengan dosis menengah. Penggunaan liposom sebagai pembawa obat, dalam hal ini metilprednisolon palmitat (MPLP) diharapkan dapat menurunkan efek samping yang ditimbulkan. Metilprednisolon palmitat adalah senyawa yang berhasil diinkorporasi ke dalam membran liposom, membentuk L-MPLP. Penelitian ini bertujuan: 1) menilai efek biologik L-MPLP sebagai senyawa Baru, yaitu dengan menilai secara kuantitatif kadar TNF a yang diperoleh dari kultur limpa mencit jantan galur C3H menggunakan ELISA, setelah 48 jam pemberian MPLP intravena dengan dosis 2 mg/kg BB, 8mg/kg BB dan 16 mg/kg BB dan pemberian L-MPLP ke dalam kultur secara in vitro dengan konsentrasi 5x 10"3 mM, 5 x10`2 mM dan 5 x104 mM, dibandingkan dengan kontrol metilprednisolon (MPL). 2) Mengetahui apakah MPLP atau metabolitnya akan terdistribusi di hepar dan limpa dengan kadar yang lebih tinggi dibandingkan dengan MPL pada jangka waktu dan pemberian yang sama, yang diukur dengan menggunakan TLC. Perhitungan kadar diiakukan menggunakan grogram Presto Page Manager dan Adobe Photo Shop 5.0. Hasil dan Kesimpulan : Pada kultur in vivo, L-MPLP dengan dosis 8 nag/kg BB dan 16 mg/kg BB setelah 48 jam pemberian, menyebabkan hambatan proliferasi limfosit (penekanan kadar TNF a), yang berbeda bermakna (pc-0,05) dibandingkan kontrol MPL. Sedangkan pada kultur in vitro, L-MPLP dengan konsentrasi 5 x 10-1 mM menyebabkan hambatan proliferasi limfosit (penekanan kadar TNF a) yang berbeda bermakna (p<0,05) dibandingkan kontrol MPL . Distribusi MPLP atau metabolitnya di hepar dan limpa, walaupun tidak bermakna secara statistik (p>0,05), tetapi menunjukkan kecenderungan terdistribusi di hepar dan limpa dengan kadar yang lebih tinggi dibanding dengan kontrol MPL."

"This study is proposed to solve the main problem in the first experiment which has the pitfall of the incorporation of methylprednisolone (MPL) into liposome's membrane. The liposomal-methylprednisolone (L-MPL) has already been formulated by Mishina, et at31.32 and experimented on several studies of organ transplantation in rat, successfully. But, all procedures even using other combination and ratio of lipids are irreproducible methods. The pitfall of the incorporation of MPL into liposome's membrane is caused by the micelle formation of MPL.To reduce or may be to inhibit the micelle formation of MPL that usually formed spontaneously when it is dispersed in aqueous media, the reactive -OH group at C21 position should have been esterified with palmitate to enhance the lipophilicity of the drug. This reaction, based on the Benameur's method, yielded 71% of pure methylprednisolonepalmitate (MPLP) as a new drug. To analyze the properties of this drug such as the stability or the availability of the drug both in liposome's membrane and in several organs in vivo, several studies have already been done in this study using sophisticated equipment.The incorporation of the new drug , MPLP, into liposome's membrane of a conventional liposome of Egg-yolk Phosphatidylcholine (EPC) was 70 %_ The incorporation was increased to approximately 95 % in liposome's membrane of EPC and tetra ether lipids (TEL) from Sulfolobus acidocaldarius as a stabilizer of the liposomal membrane The newest drug that is proposed in evaluating the stability of the drug in vitro and the distribution of the drug on several organs in mice is liposomal- methylprednisolone-palmitate (L-MPLP).The stability of L-MPLP in vitro was evaluated on their particle size. They were more stable at 20° C for 9 days of incubation than at room temperature. In vivo study of L-MPLP were shown as a distribution of the metabolite of MPL or MPLP on several organs on TLC where the distribution in the liver has more higher than in the spleen, kidney, thymus, and bone-marrow, in sequence. The distribution of the metabolite of L-MPLP in the liver has also shown higher than the metabolite of the control group of liposome, MPL, or MPLP as a free drug.Because of these successful results, this experiment will have to be continued to improve the stability of this drug and to analyze the other effects on immunosuppressive properties, toxicity, pharmacokinetics and pharmacodynamics of the drug."

"Penelitian ini dilakukan untuk menganalisis distribusi liposomal-metilprednisolon palmitat (L-MPLP) di beberapa organ pada mencit C3H setelah pemberian secara intra-peritoneal. Sebagai formula baru, L-MPLP pada membran liposom meningkat dari 70% menjadi 95% setelah digunakan tetra eter lipid dalam komposisi liposom sebagai penstabil membran. Atas dasar penelitian tersebut, L-MPLP akan terdistribusi dengan lebih baik di beberapa organ pada mencit dibandingkan control yaitu MPLP sebagai obat bebas, metilprednisolon (MPL) sebagai standar dan liposom tanpa obat. Empat puluh dua mencit C3H dibagi ke dalam 5 grup penelitian. Setiap grup dibagi ke dalam 6 waktu penelitian. Setiap obat disuntikkan intra-peritoneal. Darah diambil dari vena ekor (menit ke 10; 30; 60; 90; 180 dan jam ke 48) dan dilakukan ekstirpasi organ (hepar, limpa, timus, ginjal dan sumsum tulang) pada menit ke setalah mencit dimatikan dengan eter. Distribusi L-MPLP dalam organ tampak jelas pada menit ke 180 dan menurun setelah 48 jam. Distribusi obat atau metabolitnya tampak menonjol pada hepar, diikuti secara berurutan oleh limpa, timus, ginjal dan sumsum tulang.

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The Distribution of Liposomal-Methylprednisolone Palmitate (L-MPLP) in Several Organs in Mice after Intra-Peritoneal Injection. This study was to analyze the distribution of liposomal-methylprednisolone palmitate (L-MPLP) as a new drug formulation, in several organs of mice after intra-peritoneal injection. In a previous study, in vitro, the stability and the incorporation of methylprednisolone palmitate into liposome membranes were increased, from 70% to approximately 95% using tetra-ether lipid as a stabilizer of the liposome membrane. Based on this result, the stability of L-MPLP should also be proved, in vivo, that the drug, methylprednisolone palmitate, could be distributed into several organs more effective than in a control group (methylprednisolone palmitate and methylprednisolone as a standard of drug and liposome). Forty-two mice of C3H were divided into 5 study groups. Each group of animals was divided into 6 sub-groups of time from 10 minutes to 48 hours. Each drug was injected intra-peritoneal, blood was drawn from the vein of the tail and the organs i.e. liver, kidneys, spleen, thymus, and bone marrow were extirpated after sacrificing the mice using ether. The distribution of the drug or their metabolites was higher at the minute of 180 and tended to decrease at the time of 48 hours after injection. The higher distribution was shown in the liver and rather high in the spleen, thymus, kidney, and bone-marrow respectively."