Ronny Martien
Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Yogyakarta, Sekip Utara Yogyakarta 55281, Indonesia

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ISOLATION AND CLONING OF ENV-TM SUBUNIT GENE OF JEMBRANA DISEASE VIRUS IN THE PROKARYOTIC EXPRESSION VECTOR pGEX-2T Kusumawati, Asmarani; Martien, Ronny; Mangkoewidjojo, Soesanto; Widada, Joeannes Sri
Jurnal Sain Veteriner Vol 21, No 2 (2003)
Publisher : Fakultas Kedokteran Hewan

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POTENSI PENGGUNAAN KITOSAN RANTAI PENDEK SEBAGAI PEMBAWA DALAM PENGHANTARAN GEN; EVALUASI IN VITRO Winarti, Lina; Martien, Ronny; Sismindari, S
STOMATOGNATIC- Jurnal Kedokteran Gigi Vol 10, No 2 (2013)
Publisher : Fakultas Kedokteran Gigi Universitas Jember

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Gene therapy involves the introduction of DNA or ribonucleic acid (RNA) into the target cell either to express or suppress the biosynthesis of proteins. The success of gene therapy is highly dependent on a suitable carrier system that can efficiently deliver genes in to specific desired cell with minimum cytotoxicity on target cells. Chitosan is interesting to be used as a gene carrier because it has a high positive charge and low toxicity to cells. Positive charge chitosan can form complexes with the plasmid. DNA complexes provide protection against enzymes degradation and promote internalization of plasmids that have been condensed. In this study the complex formation of chitosan-pEFneo-GFP and chitosan / TPP-pEFneo-GFP is by complex coaservation method. The results of complex analysis with a 0.8% agarose gel electrophoresis for 30 minutes 100Volt showed that the complex was stayed in the well and the plasmids did not migrate like plasmids which were dissolved in the water and buffer solvent. Stability evaluation in storage at room temperature for 14 days showed that the complex with chitosan concentration 0.02%-0.04% were the most stable, so that transfection analysis performed for the complex with chitosan concentration of 0.02%-0.04%. Transfection results showed that chitosan is able to protect plasmid and promote the internalization of plasmid into the nucleus and then expressed as a green luminescence. From these results chitosan potentially be developed as a carrier system in gene delivery.
Review Rheumatoid Arthritis: Terapi Farmakologi, Potensi Kurkumin dan Analognya, serta Pengembangan Sistem Nanopartikel Chabib, Lutfi; Ikawati, Zullies; Martien, Ronny; Ismail, Hilda
JURNAL PHARMASCIENCE Vol 3, No 1 (2016): JURNAL PHARMASCIENCE
Publisher : JURNAL PHARMASCIENCE

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Rheumatoid arthritis  (RA) adalah  penyakit  autoimun  yang menyebabkan  peradangan  kronis  pada sendi. Penatalaksanaan RA harus agresif dan sedini mungkin sehingga mampu meningkatkan hasil jangka pendek maupun panjang penderita. Rheumatoid arthritis akibat reaksi autoimun dalam jaringan sinovial yang melibatkan proses fagositosis. Tujuan dari pengobatan rheumatoid arthritis tidak hanya mengontrol gejala penyakit, tetapi juga penekanan aktivitas penyakit untuk mencegah kerusakan permanen. Penderita RA memulai pengobatan mereka dengan DMARDs (Disease Modifying Anti-Rheumatic Drugs) seperti metotreksat, sulfasalazin dan leflunomid. Alternatif pengobatan yang dapat dijadikan salah satu pilihan dalam penanganan RA yaitu senyawa kurkumin dan analognya. Sistem nanopartikel mampu meningkatan efektifitas dalam pengobatan terutama keadaan RA. Kata kunci : rheumatoid arthritis, Disease Modifying Anti-Rheumatic Drugs, kurkumin, nanopartikel.
Formulation of nanoparticles from short chain chitosan as gene delivery system and transfection against T47D cell line Winarti, Lina; Martien, Ronny; ., Sismindari
INDONESIAN JOURNAL OF PHARMACY Vol 22 No 3, 2011
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (315.858 KB) | DOI: 10.14499/indonesianjpharm0iss0pp204-211

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Recently numerous prototype DNA-based biopharmaceuticals can be used to  control  disease  progression  by  induction  and  inhibitin  the  overexpression  of genes.  Since  there  are  poor  cellular  uptake  and  rapid  in  vivo  degradation  of DNA-based  therapeutics  therefore  the  use  of  delivery  systems  to  facilitate cellular internalization and preserve their activity is necessary. Cationic polymers commonly used as carriers to delivery gene because of easy to form complexes and  higher  stability  compared  to  that  lipoplexs.  Chitosan,  a  cationic,  are polymer most widely used in gene delivery systems because of the low toxicity, and biocompatible. The aim of this study was to formulate nanoparticles of short chain  chitosan-pEGFP-C1  and  short  chain  chitosan/TPP-pEGFP-C1  by coaservation  complex  method.  Stability  test  of  the  formula  was  performed  by incubating the nanoparticles complex with DNase I and Artificial Intestinal Fluid. Cytotoxicity  and transfection  studies  were  evaluated  against  T47D  cell line.  The diameter  of  Chitosan-pEGFP-C1  and  chitosan/TPP-pEGFP-C1  nanoparticles  were on the range of 56–282.8 nm. The zeta potential wasdetermined to be +14.03 - +16.6  mV.  Stability  studies  showed  that  chitosan-pEGFP-C1  and  chitosan/TPPpEGFP-C1  nanoparticles  were  stable,  undegradable  by  DNase  I  and  artificial intestinal fluid. Cytotoxic Assay of Chitosan-pEGFP-C1 and  chitosan/TPP-pEGFPC1  nanoparticles  (pH  4.0)  showed  that  the  viability  of cell  was  >  90%  for  all formulas.  EGFP-C1  plasmid  gene  delivered  by  chitosan  nanoparticles  can  be expressed  in  T47D  cell  culture.  According  to  these  results  chitosan  and chitosan/TPP  nanoparticles  had  potentially  to  be  used  as  a  non-viral  vector system delivery for gene therapy.Key words:Chitosan, Nanoparticles, Plasmid EGFP-C1, Cell culture T47D 
FORMULATION OF NANOCURCUMIN USING LOW VISCOSITY CHITOSAN POLYMER AND ITS CELLULAR UPTAKE STUDY INTO T47D CELLS Chabib, Lutfi; Martien, Ronny; Ismail, Hilda
INDONESIAN JOURNAL OF PHARMACY Vol 23 No 1, 2012
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (818.121 KB) | DOI: 10.14499/indonesianjpharm0iss0pp27-35

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Using  of  curcumin  as  anti  cancer  agent  is  restricted  by  its low  solubility,  therefore  it  has  low  bioavability.  This  obstacle  can be  solved  by  the  development  of  curcumin  nanoparticle. Nanoparticle  technology  has  been  started  to  be  developed  as  an alternative  solution to  improve drug  delivery pofile, especially  for the less bio-available chemical. This study was aimed to develope nanocurcumin  formulation  with  low  viscosity  chitosan  as  the matrix  and  to  study  its  ability  to  be  taken  into  the cells in  vitro. Method  used  in  the  formulation  of  nanocurcumin  in  this  study  is by ionic gelation followed by freeze drying. Entrapment  Efficiency then  assayed,  and  its  stability  was  tested  by  incubating  the formula  into  artificial  intestinal  fluid  (AIF).  Furthermore,  its toxicity  was  evaluated,  also  its  cellular  uptake  ability  into  T47D cell  line.  It  was  found  that  the  Entrapment  Efficiency  in  acetate buffer  at  pH  4  is  higher  than  at  pH  5.  This  formula  also  has  a good  stability  in  AIF.  For  the  cellular  uptake  study  through fluorescence  microscope,  it  was  found  that  the  complex  has  an ability  to  penetrate  cellular  membrane  into  the  cytosol.  The cytotoxicity  study  tell  us  that  the  nanocurcumin  is  non-toxic  to normal  cell line. For  the characterization of the nanoparticles, the average  size  of  this  particle  is  269.8  nm,  its  zeta-potential  is +18.63 mV, with spherical particle morphology. From the result ofthis study, it is concluded that formulation of nanocurcumin using low viscosity chitosan polymer as the matrix has a great potential as an alternative for anticancer therapy.Key words: nanoparticle, curcumin, low viscosity chitosan, T47D cell line. 
Formulation of Medium Viscosity Chitosan-Pectin –MJ Protein Nanoparticles Conjugated with Anti-Ep-CAM and Its Cytotoxicity Against T47D Breast Cancer Cell Lines Feranisa, Anggun; Arimurni, Dewa Ayu; Ismail, Hilda; Martien, Ronny; Sismindari, S.
Indonesian Journal of Biotechnology Vol 20, No 1 (2015)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.15283

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Chitosan nanoparticle could become potential formula to protect protein degradation during therapy,since chitosan nanoparticles have “proton sponge hypothesis” mechanism on its protection. Chitosan and pectinis used as basic formula of drug delivery because of its biodegradable and biocompatible properties. Chitosanpectin nanoparticles can be formulated by polyelectrolit complex. EpCAM showed excessive expression inepithelial cancer cells thus can be used as a therapeutic biomarker. MJ protein, a Ribosome-Inactivating Proteins(RIPs) isolated from Mirabilis jalapa L had a higher cytotoxicity on malignant cells than normal cells. MJ proteinneed to be formulated to protect from proteosome degradation in endosome. The aim of this research was todevelop MJ protein-chitosan-pectin nanoparticles and conjugated with anti EpCAM for breast cancer therapy.Mj protein was extracted from M.jalapa leaves. RIPs activity was assayed by supercoiled DNA cleavage. MJprotein were loaded into chitosan nanoparticles using medium viscous chitosan and pectin as cross-linker withpolyelectrolit complex method. Anti EpCAM was conjugated to MJ protein-chitosan-pectin nanoparticles bycarbodiimide reaction and characterized for its entrapment efficiency, morphology by transmission electronmicroscope, particles size, and zeta potential. MJ protein nanoparticles conjugated anti EpCAM and withoutanti EpCAM were cytotoxicity assayed toward T47D and Vero cell lines. MJ protein was able to cleave thesupercoiled DNA into linear and nicked-circular ones. The nanoparticles optimal concentration of mediumviscous chitosan: MJ protein: pectin was 0.01%: 0.01%: 1% (m/v). A high entrapment efficiency of MJ proteinnanoparticles was 98.97 ± 0.07%. Morphology nanoparticles showed an amorphic structure with 200.00 nmparticles size. The nanoparticles conjugated anti EpCAM showed average particles size 367.67nm, polydispersityindex 0.332, and zeta potential +39.97mV. MJ protein-chitosan-pectin nanoparticles conjugated anti EpCAMand unconjugated both had higher cytotoxicity with the IC50 57.64 μg/mL and 46.84 μg/mL respectivelyagainst T47D and 99.38 μg/mL and 111.34 μg/mL against Vero cell lines compared to MJ protein with IC50 of3075.61 μg/mL against T47D and 3286.88 μg/mL against Vero cell lines. Both MJ protein-nanoparticles couldincrease the cytotoxicity effects about 50 times compared to the unformulated MJ protein activity, howeverhad less specificity toward T47D and Vero cell lines.
PREPARASI NANOPARTIKEL GAMAVUTON-0 MENGGUNAKAN KITOSAN RANTAI PENDEK DAN TRIPOLIFOSFAT SEBAGAI CROSS LINKER Taurina, Wintari; Martien, Ronny; Ismail, Hilda
Jurnal Ilmiah Farmasi Vol 10, No 2 (2013)
Publisher : Jurnal Ilmiah Farmasi

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.20885/jif.vol10.iss2.art4

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Gamavuton-0 (GVT-0) adalah suatu senyawa hasil modifikasi molekul kurkumindengan potensi analgetika dan anti inflamas iyang terbukti cukup baik. Saat ini pemberian senyawa GVT-0 sangat terbatas melalui rute parenteral, karena rendahnya bioaviabilitas senyawa pada pemberian secara peroral. Hal ini disebabkan karena sifat-sifat fisikokimia GVT-0 yang tidak menguntungkan (hidrofilisitas, ukuran molekul, dan densitas muatan negatif) yang menyebabkan permeabilitasnya terhadap intestinal menjadi buruk. Keterbatasan tersebut dapat diatasi dengan sistem nanopartikel. Penelitian ini bertujuan untuk mengembangkan nanopartikel GVT-0 dengan pembawa kitosan rantai pendek sebagai sebuah sistem penghantaran obat per oral. Pada penelitian ini nanopartikel GVT-0 diformulasikan menggunakan metode ionik gelasi dengan penambahan tripolifosfat (TPP) yang bermuatan negatif. Nanopartikel akan dikarakterisasi menggunakan TEM dan PSA untuk melihat morfologi dan ukurannya, kemudian dilakukan uji Entrapment Efficiency. Selanjutnya dilakukan uji stabilitas di dalam HCl dan AIF. Nanopartikel GVT-0 yang dipreparasi mempunyai ukuran partikel ratarata antara 504,7 nm - 638,2 nm dan umumnya mempunyai bentuk sferik. Entrapment Efficiency yang diperoleh yaitu antara 30,27% - 71,63%. Nanopartikel GVT- 0 relatif stabil dalam HCl 0,1N pH 1 sampai jam ke-3 dengan stabilitas antara 53,03 - 83,56%, dan dalam AIF sampai jam ke-4 dengan stabilitas antara 63,08 - 97,08%. Berdasarkan hasil penelitian terlihat bahwa GVT-0 dan kitosan rantai pendek dapat dipreparasi menjadi nanopartikel GVT-0 yang stabil dalam AIF dan HCl 0,1N pH 1.
THE DISSOLUTION AND DIFFUSION OF FUROSEMIDE ON SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) wahyuningsih, iis -; Sugiyanto, Sugiyanto; Yuswanto, Ag.; Martien, Ronny
INDONESIAN JOURNAL OF PHARMACY Vol 28 No 2, 2017
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (699.486 KB) | DOI: 10.14499/indonesianjpharm28iss2pp112

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Furosemide a diuretic exhibits low solubility in water and low bioavailability. The purpose of this study was to determine the effect SNEDDS formation to dissolution and diffusion of furosemide. SNEDDS was made with a mixture of 66% tween 80, 26% propylene glycol, 8% oleic acid and furosemide 40mg/mL. Test for SNEDDS dissolution of the capsules was developed using USP dissolution apparatus I and compared to market products, furosemide suspenssion and furosemide powder. The medium consists of 900mL of Artificial Gastric Fluid (AGF) , phosphate buffer pH 5.8 at 37±0.5°C and stirred with a speed of 100rpm. Diffusion test of SNEDDS furosemide was conducted by using reversed rat intestinal bowel and compared to furosemide suspension and furosemide solution. The SNEDDS formulation  could enhance the dissolution and diffusion of furosemide compared to the non-SNEDDS formulation
AKTIVITAS DIURETIK SELF-NANOEMULSIFYING DRUG DELIVERY SYSTEM (SNEDDS) FUROSEMID wahyuningsih, iis; sugiyanto, sugiyanto; Yuswanto, Ag; martien, ronny
Farmasains : Jurnal Ilmiah Ilmu Kefarmasian Vol 4 No 1 (2017)
Publisher : Universitas Muhammadiyah Prof. DR. HAMKA

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22236/farmasains.v4i1.3360

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Furosemide is a diuretic having low solubility and low bioavailability thus the diuretic activity is not optimal. The purpose of this study was to determine the effect of furosemide SNEDDS formation to  the diuretic activity. SNEDDS was made with a mixture of 66% tween 80, 26% propilene glycol, 8% oleic acid and furosemide 40 mg/mL. A total of 20 test animals were divided into 4 groups, namely the negative control 1 (CMC 0,5% suspension), negativ control 2 (a mixture of tween 80, propilene glycol and oleic acid), furosemid suspension and SNEDDS furosemid. Tests on the diuretic activity is done by measuring the volume of urine released for 6 hours.Furosemide SNEDDS  could enhance the diuretic activity of furosemide.
PERKEMBANGAN TEKNOLOGI NANOPARTIKEL SEBAGAI SISTEM PENGHANTARAN OBAT Martien, Ronny; Adhyatmika, Adhyatmika; Irianto, Iramie D. K.; Farida, Verda; Sari, Dian Purwita
Majalah Farmaseutik Vol 8, No 1 (2012)
Publisher : Fakultas Farmasi Universitas Gadjah Mada

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Teknologi nanopartikel saat ini telah menjadi tren baru dalam pengembangan sistem penghantaran obat. Partikel atau globul pada skala nanometer memiliki sifat fisik yang khas dibandingkan dengan partikel pada ukuran yang lebih besar terutama dalam meningkatkan kualitas penghantaran senyawa obat. Kelebihan lain dari teknologi nanopartikel adalah keterbukaannya untuk dikombinasikan dengan teknologi lain, sehingga membuka peluang untuk dihasilkan sistem penghantaran yang lebih sempurna. Keterbukaan lain dari teknologi nanopartikel adalah kemampuannya untuk dikonjugasikan dengan berbagai molekul pendukung tambahan, sehingga menghasilkan sebuah sistem baru dengan spesifikasi yang lebih lengkap. Namun, sifat umum nanopartikel yang berlaku pada berbagai jaringan maupun organ di dalam tubuh adalah sifat fisik nanopartikel yang relatif lebih mudah menembus berbagai pembatas biologis, sehingga menjadi kurang spesifik jika digunakan dengan tujuan aplikasi khusus. Oleh karena itu, molekul yang dikonjugasikan pada nanopartikel secara umum dimanfaatkan sebagai molekul pentarget untuk meningkatkan selektivitas dari sistem nanopartikel secara keseluruhan. Review ini membahas perkembangan beberapa hasil penelitian yang telah dipublikasikan selama kurun waktu beberapa tahun terakhir dalam usaha pengembangan nanopartikel sebagai sistem penghantaran obat. Beberapa topik khusus akan dipaparkan dalam review ini yaitu penggunaan biopolimer dalam sistem nanopartikel, modifikasi sistem nanopartikel pada penerapan penghantaran obat tertarget, serta nanoliposom dan nanoemulsi.