CELLULAR UPTAKE STUDY AND CYTOTOXICITY STUDY OF RESVERATROL-GOLD-PEG-FOLATE (RSV-AU-PEG-FA) NANOPARTICLES ON HELA HUMAN CERVICAL CANCER CELL LINE

Objective: This study aimed to evaluate the effectivity of resveratrol-gold-PEG-folate (RSV-Au-PEG-FA) nanoparticles formulation in resveratrol (RSV) targeted delivery and cytotoxicity effect on HeLa human cervical cancer cell line. Methods: Gold nanoparticles (AuNP) were used as carriers and folic acid (FA) was used as active targeting moiety, using polyethylene glycol-bis-amine (PEG-bis-amine) as linker. RSV-Au-PEG-FA nanoparticles were characterized by UV-Vis spectrophotometry, infrared spectroscopy, particle size analyzer (PSA), and transmission electron microscopy (TEM). Cellular uptake study was conducted by using fluorescence microscope. Cytotoxicity study was conducted by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: Cellular uptake study has shown that RSV-Au-PEG-FA nanoparticles are potential to be accumulated intracellularly in HeLa cells more than in Vero cells. Cytotoxicity study has shown RSV-Au-PEG-FA nanoparticles IC50 67.06±2.14 mM and RSV IC50 9.66±1.44 mM on HeLa cells Conclusion: RSV-Au-PEG-FA nanoparticles are potential to enhance RSV uptake by HeLa cells selectively

SYNTHESIS AND STABILITY TEST OF RESVERATROL-CONJUGATED GOLD NANOPARTICLE WITH POLYVINYL ALCOHOL STABILIZATION

Objective: Gold nanoparticles (AuNPs) have been developed as a promising effective site-specific drug to increase drug efficacy and reduce potentialside effects. However, AuNPs are unstable because they easily aggregate. This study aims to produce stable resveratrol (RSV)-conjugated AuNPs usingpolyvinyl alcohol (PVA).Methods: AuNPs were synthesized using the Turkevich method, which involves the reduction of chloroauric acid with sodium citrate as a reductor.AuNPs were then modified with PVA as a stabilizing agent and conjugated with RSV as a drug model in the carrier system. The formed conjugates werecharacterized using ultraviolet–visible spectrophotometry, Fourier transform infrared spectroscopy, particle size analysis, and high-performanceliquid chromatography. Furthermore, stability tests were performed in various media (2% bovine serum albumin [BSA], 1% cysteine, phosphatebufferedsaline [PBS] pH 4, PBS pH 7.4, and 0.9% NaCl) for 28 days.Results: RSV–AuNPs–PVA had a particle size of 78.75 nm, with polydispersity index (PDI) of 0.356, zeta potential of −36.1 mV, and highest entrapmentefficiency of 78.1%±0.7. RSV–AuNPs without PVA stabilization had a particle size of 51.97 nm, with PDI of 0.694 and zeta potential of −24.6 mV. Theresults of the stability tests demonstrated that RSV–AuNPs–PVA was stable in 2% BSA, PBS pH 7.4, PBS pH 4, and NaCl 0.9% and were unstable in 1%cysteine. RSV–AuNPs without PVA were stable in 2% BSA and PBS pH 7.4 and unstable in 1% cysteine, PBS pH 4, and 0.9% NaCl.Conclusion: PVA can improve the physical stability of RSV-AuNPs conjugates

PREPARATION AND CHARACTERIZATION OF SODIUM CARBOXYMETHYL CELLULOSE FROM KAPOK (CEIBA PENTANDRA) ALPHA-CELLULOSE

Objective: This study aimed to obtain sodium carboxymethyl cellulose (NaCMC) from α-cellulose of the hulls of kapok (Ceiba pentandra) anddetermining its identity and characteristics base on compendial requirements and compared to the reference (standard).Methods: α-Cellulose was isolated from kapok hulls and used to generate NaCMC powder through alkalization and carboxymethylation. Alkalizationwas performed using 25% NaOH (containing sodium tetraborate), whereas carboxymethylation was using sodium monochloroacetate. Identificationand characterization were performed through infrared spectrum analysis using Fourier transform infrared, qualitative analysis, organolepticexamination, morphologic examination, and topographical analysis using scanning electron microscopy (SEM), and X-ray diffraction. Tests conductedwere pH determination, sulfated ash content, moisture content, loss on drying, particle density, and viscosity.Results: The obtained NaCMC powder was yellowish-white with a similar infrared spectrum as the NaCMC standard. The powder had a degreeof substitution of 0.57 and a pH of 8.5. According to SEM, the obtained powder had a similar morphology as the NaCMC standard, although thesynthesized NaCMC had a rougher surface. The obtained NaCMC also had a similar diffractogram as the NaCMC standard, which was characterizedby the presence of crystalline and amorphous structures. Besides, the NaCMC powder had a similar moisture content (8.50%), sulfated ash content(36.43%), and loss on drying (9.87%) as the standard, whereas its 1% viscosity value (20.6 cP) was substantially different.Conclusion: NaCMC generated from α-cellulose of kapok hulls fulfills compendial requirements and has similar characteristics to reference

SYNTHESIS AND STABILITY OF RESVERATROL-CONJUGATED GOLD NANOPARTICLES MODIFIED WITH POLYETHYLENE GLYCOL

Objective: Gold nanoparticles (AuNPs) are highly useful for drug delivery, but their application is limited by their stability as they readily aggregate.This issue can be prevented by adding a stabilizing agent such as resveratrol (RSV), which is a polyphenol derived from plants, that is used to preventcancer. Therefore, we propose a novel method to prepare stable RSV-conjugated nanoparticles modified with polyethylene glycol (RSV-AuNP-PEG).Methods: In the first step, the Turkevich method was used to synthesize the AuNPs. Then, PEG was added as stabilizer agent and conjugated with RSV.The synthesized conjugates were characterized using ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, particle sizeanalysis, and high-performance liquid chromatography.Results: The obtained RSV-AuNP-PEG had a particle size of 83.93 nm with a polydispersity index (PDI) of 0.562 and formed a translucent purple-redfluid in solution. The zeta potential was −22.9 mV, and the highest entrapment efficiency was 75.86±0.66%. For comparison, the RSV-AuNP solutionwas purple and turbid, the particle size was 51.97 nm with a PDI of 0.694, and the zeta potential was −24.6 mV. The stability test results showed thatthe storage stability of RSV-AuNP-PEG was better than that of AuNP-RSV. Further, the RSV-AuNP-PEG was shown to be most stable in 2% bovine serumalbumin (BSA) while the AuNP-RSV was most stable in 2% BSA in phosphate-buffered saline pH 7.4.Conclusion: These results show that modification of RSV-conjugated AuNPs with PEG effectively prevents their aggregation in storage, but only incertain mediums

Pengembangan Sediaan Dengan Pelepasan Dimodifikasi Mengandung Furosemid Sebagai Model Zat Aktif Menggunakan Sistem Mukoadhesif

Drug bioavailability is one of the parameter which is used to evaluate the effectiveness of pharmaceutical dosage form. Rate of dissolution and drug residence time in gas-trointestinal tract is a factor which can influence the bioavailability. Solid dispersion and mucoadhesive drug delivery system is one of the method which can be used to solve the problem concerning the rate of dissolution and residence time in gastrointes-tinal tract. In this research mucoadhesive microgranule had been made with furo-semide as a drug model and Carbopol 934P® as a mucoadhesive polimer. The mucoadhesive microgranules resulted from this investigation has a particle size rangeof 425-850 µm, and was evaluated by type 1, 100 rpm speed and phosphate buffer pH 5.8 dissolution test and by wash off test. Furosemide was made in solid dispersionwith polyvinylpyrrolidone (PVP K30®) with weight ratio of 1:7 using solubility method. The results showed increasing the dissolution rate of furosemide in solid dispersion compared to pure furosemide. Increasing the concentration of Carbopol934P® in microgranule will cause inhibition of drug release and increasing the amount of microgranule sticked to gastric and intestinal mucous

SYNTHESIS AND STABILITY OF RESVERATROL-GOLD NANOPARTICLE-POLYETHYLENE GLYCOL-FOLIC ACID CONJUGATES

Objective: Gold nanoparticles (AuNPs) can be used as targeted drug delivery systems, however, AuNPs have high surface energy and easily aggregate,thus negatively impacting nanoparticle stability. Therefore, it is necessary to add a stabilizing agent to AuNPs. To synthesize AuNPs stabilized bypolyethylene glycol conjugated to folic acid (FA), thus creating a model drug (resveratrol [RSV]) carrier that targets FA receptors on cancer cells.Methods: AuNPs were synthesized using the Turkevich method and stabilized by adding FA conjugated to polyethylene glycol (PEG). After RSV wasloaded, the conjugate was physically characterized and subjected to stability tests.Results: The RSV-AuNP had an average particle size of 51.97 nm (polydispersity index [PDI] 0.694, zeta potential – 24.6 mV). The RSV-AuNP-PEG-FAconjugate (RSV-AuNP-PEG-FA) had an average particle size of 195.6 nm (PDI=0.233, zeta potential=−21.1 mV). Stability tests showed that RSV-AuNPPEG-FA was more stable than RSV-AuNP. Furthermore, RSV-AuNP-PEG-FA and RSV-AuNP were more stable in buffer pH 7.4 and bovine serum albumin2% than in buffer pH 4, cysteine 1%, and NaCl 0.9% solutions.Conclusion: PEG-FA conjugates can improve the stability of RSV-loaded AuNP

PERLINDUNGAN HUKUM TERHADAP PENGENDARA YANG MENGAKIBATKAN HILANGNYA NYAWA SESEORANG YANG DISEBABKAN OLEH KELALAIAN KEDUA BELAH PIHAK DIJALAN RAYA

Research with the title Legal Protection of Riders Resulting in the Loss of a Person's Life Due to the Negligence of Both Parties on the Highway (Analysis of the Supreme Court Decision Number 2 / Pid.Sus / 2018 / PN.Mbo). Aiming to find out the legal settlement process against motorists who resulted in the loss of one's life due to negligence of both parties on the road and to find out the implementation of legal protection for motorists who resulted in the loss of one's life due to negligence of both parties on the road. This study uses the normative (normative) juridical method, namely research by observing and paying attention to the prevailing legal norms and being connected according to the facts of the problems in the study. The results of the research are the first, namely: the process of criminal justice settlement, investigation, prosecution, examination process in court. Second, namely: protection is the right of the suspect or defendant and the role of restoration of justise as an attempt by the suspect to be forgiven by the victim's family. Keywords: Legal Protection, Rider, Life, Negligence, HighwayPenelitian dengan judul Perlindungan Hukum Terhadap Pengendara Yang Mengakibatkan Hilangnya Nyawa Seseorang Yang Disebabkan Oleh Kelalaian Kedua Belah Pihak Dijalan Raya (Analisis Putusan Mahkamah Agung Nomor. 2/Pid.Sus/2018/PN.Mbo). Bertujuan untuk mengetahui proses penyelesaian hukum terhadap pengendara yang mengakibatkan hilangnya nyawa seseorang yang disebabkan oleh kelalaian kedua belah pihak dijalan raya serta untuk mengetahui pelaksanaan perlindungan hukum terhadap pengendara yang mengakibatkan hilangnya nyawa seseorang yang disebabkan oleh kelalaian kedua belah pihak dijalan raya. Penelitian ini menggunakan metode yuridis normatif (normatif) yakni penelitian dengan melihat dan memperhatikan norma hukum yang berlaku dan dihubungkan sesuai fakta dari permasalahan dalam penelitian. Hasil dari penelitian, yang pertama yaitu : Proses penyelesaian hukum tindak pidana, penyidikan, penuntutan, proses pemeriksaan di pengadilan. Yang kedua yaitu : perlindungan ialah hak tersangka atau terdakwa dan peran restorasi justise sebagai upaya tersangka untuk dimaafkan oleh keluarga korban. Kata Kunci: Perlindungan Hukum, Pengendara, Nyawa, Kelalaian, Jalan Ray

Pengaruh Natrium Hialuronat Terhadap Penetrasi Kofein Sebagai Antiselulit Dalam Sediaan Hidrogel, Hidroalkoholik Gel, Dan Emulsi Gel

Anticellulite topical gel preparation with caffeine as active ingredient needs a penetration enhancer to reach subcutaneous layer. Sodium hyaluronate (NaHA), the sodium salt of hyaluronic acid, is a hydrophilic polysaccharide derivative polymer. It has ability to enhance percutaneous penetration by loosening the dense of the compact substance stratum corneum. The aim of this research was to observe the effects of NaHA on caffeine penetration as anticellulite active agent in three types of gel preparation: hydrogel, hydroalcoholic gel, and gel emulsion. Each gel type contained caffeine 1,5% and was varied into three formulas. Formula 1 contained HPMC 2% as gel basis; formula 2 contained HPMC 2% and NaHA 0,5%; formula 3 contained NaHA 2% as gel basis. Caffeine penetration properties were analyzed by Franz diffusion cell in vitro test using rat skin as membrane. Percent caffeine penetration of hydrogel formula 1, 2, 3 were 9,41 ± 0,01%; 11,74 ± 0,13%; 16,32 ± 0,03%, respectively. Percent caffeine penetration of hydroalcoholic gel formula 1, 2, 3 were 19,54 ± 0,02%; 22,99 ± 0,23%; 7,42 ± 0,08%, respectively. Percent caffeine penetration of gel emulsion formula 1, 2, 3 were 10,47 ± 0,19%; 13,41 ± 0,12%; 18,42 ± 0,06%, respectively. The result showed that NaHA enhanced the caffeine percutaneous penetration properties in various gel preparations, except hidroalkoholic gel formula 3

Mikroenkapsulasi Propanolol Hidroklorida Dengan Penyalut Etil Selulosa Menggunakan Metoda Penguapan Pelarut

Propranolol hydrochloride is antihypertension agent that has a short biological half life of 2-6 hours. Microcapsules of propranolol hydrochloride are prepared by solvent evaporation method using ethylcellulose as a wall material with the drug-polymer ratio 1:1, 1:2, and 1:3 for sustained release oral delivery. The microcapsules were then evaluated by particle size distribution analysis, shape and morphology (SEM), drug content, and dissolution studies. In vitro dissolution was studied using the dissolution apparatus II (paddle) with chloride buffer (pH 1,2) dan phosphate buffer (pH 6,8) medium. The drug-polymer ratio have an important influence on drug release from microcapsules where the increase of polymer cause the higher drug release inhibition

Pengaruh Polivinil Pirolidon Terhadap Laju Disolusi Furosemid Dalam Sistem Dispersi Padat

The research to accelerate furosemide dissolution rate has been done through physical property modification by solid dispersion forming polyvinylpyrolidone (PVP) carrier with solvent method. Pure furosemide posses property of being practically insoluble in water and has low bioavailability. In current research, six weight ratio of furosemide to PVP being used are 1:1; 1:3; 1:5; 1:9 and 1:15. Physical mixtures are made in equivalent weight ratio. The dissolution rate was examined by paddle method in phosphat buffer pH 5,8. Solid dispersion caracterised with in vitro dissolution study, X-ray diffraction, infra red spectrophotometer and differential scanning calorimetric. The result shows that solid dispersion of furosemide with PVP carrier is higher compare to physical mixture dissolution rate and pure furosemide. The ratio furosemide to PVP who has the highest dissolution rate is 1:15. The analyzing shows the existing of altering crystalline to amorphous state