FORMULATION AND EVALUATION OF RED PALM OLEIN NANOEMULSION

Objective: The objective of this study is to formulate and evaluate the red palm olein (RPO) nanoemulsion using spontaneous emulsification method.Methods: Nanoemulsion formulated by spontaneous emulsification method using the comparison of surfactant (tween 80) and cosurfactant (sorbitol) concentration with the variation of RPO concentration. Evaluation of the stability of the nanoemulsion preparation includes centrifugation test, viscosity, pH, organoleptic observation (odor, color, clarity, and phase separation), and particle size measurement during 12 weeks storage at room temperature.Result: The results showed that all nanoemulsion preparations were transparent yellow, characteristic odor, type weights 1.0166–1.0641 g/ml, and stable for 12 weeks storage at room temperature. The smallest particle size was produced by the nanoemulsion preparation in a formula of the concentration of 5%, which was 67, 64 nm.Conclusion: RPO can be formulated as a nanoemulsion by spontaneous emulsification method. RPO with a 5% concentration is very stable for 12 weeks storage

Pengaruh Kandungan Komponen Minor dari Minyak Kelapa Sawit (Elaeis guineensis Jacq.) Terhadap Aktivitas Antioksidan pada Proses Pemurnian Karotenoid

Palm oil contains carotenoid and vitamin E which possess an antioxidant properties . A long exposure of heat and chemical substances during the purification process may lower the antioxidant activity. This research was conducted to compare antioxidant activity of carotenoid and vitamin E obtained from each stage of three continuous purification process (transesterification, solvolytic micellization, and saponification). Total carotenoid concentration was analyzed by UV-visible spectrophotometer at λ 446 nm and total vitamin E concentration was analyzed by high-performance liquid chromatography, while ester and triglyceride concentration were analyzed by gas chromatography. Antioxidant activity was measured by DPPH assay with 60 minutes incubation time. The highest concentration of carotenoid (229.968 mcg/ml) was extracted from saponification process, yet the highest concentration of vitamin E (97.64 mcg/ml) was extracted from transesterification process. The highest antioxidant activity of carotenoids and vitamin E was obtained from the transesterification process, while other processes had lower antioxidant activity, so it can be concluded that exposure to heat and excessive chemical substances could impact on the  antioxidant activity

NILAI EKONOMI NIRA SAWIT SEBAGAI POTENSI PEMBIAYAAN PEREMAJAAN KEBUN KELAPA SAWIT RAKYAT

Oil palm smallholder currently are more than 25 years old and have to be replanted. However, many smallholders have facing difficulties in replanting especially related to investment and loss of income during the period of immatature. Palm trunks from replanted plants have potential economic value by utilizing sap obtained by tapping inflorescences of oil palm to make brown sugar. This study aims to assess the economic value of oil palm brown sugar as a potential financing of oil palm plantation peremajaan. The study was conducted in the village of Lau Tador, Sei Suka District, Batu Baral Regency North Sumatra. The research method used was on farm participatory research survey and focus group discussions were carried out farm business analysis. Research shows that oil palm trunks have considerable economic value potential. The economic value of 1 palm trunk for oil palm brown sugar (not yet processed/straightened before being cut) is IDR. 15,813 (IDR 1,897,500 per ha). Whereas if processed into oil palm brown sugar has a potential net income per ha of IDR 18,421,500 to IDR 22,866,325 with financial analysis carried out.  This potential can help smallholders living costs and up keep costs as long as immatature. To optimize the economic potential of production, it is carried out on a wide scale through the development of farmer groups or cooperatives. Through cooperatives will be managed in an organized manner including funding, technical, production, and marketing. The utilization oil palm brown sugar can be used as one of the activities in the oil palm smallholder replanting program (PSR) which is the government's main program.Sebagian besar dari perkebunan kelapa sawit rakyat saat ini telah memerlukan peremajaan. Namun banyak pekebun rakyat mengalami kesulitan, terutama karena besarnya biaya yang dibutuhkan dan hilangnya pendapatan selama masa tanaman belum menghasilkan. Batang sawit yang ditumbangkan pada saat peremajaan memiliki potensi nilai ekonomi sehingga dapat dijadikan sebagai alternatif sumber pendapatan selama tanaman belum menghasilkan. Untuk menganalisis hal tersebut penelitian ini dilakukan di Desa Lau Tador Kecamatan Sei Suka Kabupaten Batu Bara Sumatera Utara. Metode penelitian  yang digunakan adalah on farm participatory research survey dan focus group discussion serta dilakukan analisis usaha gula merah sawit. Penelitian menunjukkan nilai ekonomi batang sawit yang belum diolah adalah sebesar Rp. 15.813. atau sebesar Rp. 1.897.500 per ha, sedangkan yang sudah diolah menjadi gula sawit memiliki potensi pendapatan bersih per ha nya sebesar Rp. 18.421.500 sampai dengan Rp. 22.866.325. Potensi ini dapat membantu biaya hidup petani dan biaya perawatan selama sawit masih dalam masa belum menghasilkan. Untuk mengoptimalkan potensi ekonomi produksi gula merah sawit dilakukan dengan skala luas melalui pembentukan kelompok tani ataupun koperasi. Melalui koperasi akan dikelola secara terorganisir baik pendanaan, teknis, produksi, maupun  pemasaran. Pemanfaatan nira sawit ini dapat dijadikan salah satu kegiatan dalam program peremajaan sawit rakyat (PSR) yang menjadi program utama  pemerintah

Improving Brain Delivery of Biomolecules via BBB Modulation in Mouse and Rat: Detection using MRI, NIRF, and Mass Spectrometry

There is an urgent need to develop new and alternative methods to deliver functional biomolecules to the brain for diagnosis and treatment of brain diseases. The goal of this study was to evaluate the activity of blood-brain barrier (BBB) modulators (i.e., HAV and ADT peptides) to deliver functional biomolecules (i.e., galbumin, IRdye800cw-cLABL, and cIBR7) to the brains of mice and rats. HAV6, cHAVc3, and ADTC5 peptides but not HAV4 peptide significantly enhanced the brain delivery of 65 kDa galbumin compared to control in Balb/c mice as quantified by magnetic resonance imaging (MRI). Ten-minute pretreatment with ADTC5 peptide still significantly increased brain delivery of galbumin; however, no enhancement was observed after 10-min pretreatment with HAV6. There was no enhancement of galbumin deposition following 40-min pretreatment with ADTC5 or HAV6, suggesting a short duration of the BBB opening for large molecules. ADTC5 peptide also improved the brain delivery of IRdye800cw-cLABL peptide about 3.5-fold compared to control in Balb/c mice as detected by near infrared fluorescence (NIRF). The BBB modulator activity of ADTC5 to deliver cIBR7 peptide was also evaluated in vivo using Sprague-Dawley rats. The amount of cIBR7 in the brain was detected by LC-MS/MS. ADTC5 peptide enhanced the delivery of cIBR7 peptide into rat brain about 4-fold compared to control and the intact cIBR7 can be efficiently extracted and detected in rat brain. In conclusion, HAV and ADT peptides enhance the brain delivery of functional peptides (e.g., cLABL and cIBR7) and protein (e.g., 65 kDa galbumin) in two animal models, and the duration of the BBB opening for a large molecule (e.g., galbumin) was short

Modulation of Intercellular Junctions by Cyclic-ADT Peptides as a Method to Reversibly Increase Blood-Brain Barrier Permeability

It is challenging to deliver molecules to the brain for diagnosis and treatment of brain diseases. This is primarily due to the presence of the blood-brain barrier (BBB), which restricts the entry of many molecules into the brain. In this study, cyclic ADT peptides (ADTC1, ADTC5, and ADTC6) have been shown to modify the BBB to enhance the delivery of marker molecules (e.g., 14C-mannitol, Gd-DTPA) to the brain via the paracellular pathways of the BBB. The hypothesis is that these peptides modulate cadherin interactions in the adherens junctions of the vascular endothelial cells forming the BBB to increase paracellular drug permeation. In vitro studies indicated that ADTC5 had the best profile to inhibit adherens junction resealing in MDCK cell monolayers in a concentration-dependent manner (IC50 = 0.3 mM) with a maximal response at 0.4 mM. Under the current experimental conditions, ADTC5 improved the delivery of 14C-mannitol to the brain about twofold compared to the negative control in the in situ rat brain perfusion model. Furthermore, ADTC5 peptide increased in vivo delivery of Gd-DTPA to the brain of Balb/c mice when administered intravenously (i.v.). In conclusion, ADTC5 has the potential to improve delivery of diagnostic and therapeutic agents to the brain

Doxorubicin-loaded iron oxide nanoparticles for glioblastoma therapy: A combinational approach for enhanced delivery of nanoparticles

This work is licensed under a Creative Commons Attribution 4.0 International License.Although doxorubicin (DOX) is an effective anti-cancer drug with cytotoxicity in a variety of different tumors, its effectiveness in treating glioblastoma multiforme (GBM) is constrained by insufficient penetration across the blood–brain barrier (BBB). In this study, biocompatible magnetic iron oxide nanoparticles (IONPs) stabilized with trimethoxysilylpropyl-ethylenediamine triacetic acid (EDT) were developed as a carrier of DOX for GBM chemotherapy. The DOX-loaded EDT-IONPs (DOX-EDT-IONPs) released DOX within 4 days with the capability of an accelerated release in acidic microenvironments. The DOX-loaded EDT-IONPs (DOX-EDT-IONPs) demonstrated an efficient uptake in mouse brain-derived microvessel endothelial, bEnd.3, Madin–Darby canine kidney transfected with multi-drug resistant protein 1 (MDCK-MDR1), and human U251 GBM cells. The DOX-EDT-IONPs could augment DOX’s uptake in U251 cells by 2.8-fold and significantly inhibited U251 cell proliferation. Moreover, the DOX-EDT-IONPs were found to be effective in apoptotic-induced GBM cell death (over 90%) within 48 h of treatment. Gene expression studies revealed a significant downregulation of TOP II and Ku70, crucial enzymes for DNA repair and replication, as well as MiR-155 oncogene, concomitant with an upregulation of caspase 3 and tumor suppressors i.e., p53, MEG3 and GAS5, in U251 cells upon treatment with DOX-EDT-IONPs. An in vitro MDCK-MDR1-GBM co-culture model was used to assess the BBB permeability and anti-tumor activity of the DOX-EDT-IONPs and DOX treatments. While DOX-EDT-IONP showed improved permeability of DOX across MDCK-MDR1 monolayers compared to DOX alone, cytotoxicity in U251 cells was similar in both treatment groups. Using a cadherin binding peptide (ADTC5) to transiently open tight junctions, in combination with an external magnetic field, significantly enhanced both DOX-EDT-IONP permeability and cytotoxicity in the MDCK-MDR1-GBM co-culture model. Therefore, the combination of magnetic enhanced convective diffusion and the cadherin binding peptide for transiently opening the BBB tight junctions are expected to enhance the efficacy of GBM chemotherapy using the DOX-EDT-IONPs. In general, the developed approach enables the chemotherapeutic to overcome both BBB and multidrug resistance (MDR) glioma cells while providing site-specific magnetic targeting.Canadian Institutes of Health ResearchNatural Science and Engineering Research Council—CanadaNIH R01-NS075374NIH P30-AG035982NIH T32-GM00835

SUMBERDAYA INDUSTRI KELAPA SAWIT DALAM MENDUKUNG SWASEMBADA DAGING SAPI NASIONAL

Indonesia masih belum mampu swasembada daging sapi hingga saat ini. Untuk mengembangkan peternakan sapi, ketersediaan pakan dan lahan menjadi faktor pembatas.  Sementara itu industri perkebunan kelapa sawit mempunyai potensi untuk menyediakan pakan sapi. Biomassa dari industri perkebunan kelapa sawit yang dapat digunakan sebagai pakan ternak sapi adalah tanaman hijauan pada kebun kelapa sawit, daun dan pelepah hasil kegiatan panen, dan BIS dan solid dari kegiatan pengolahan kelapa sawit. Berdasarkan perhitungan dan assumsi, industri kelapa sawit Indonesia mampu menyediakan pakan sapi bagi 25 juta ekor dengan menggunakan daun dan pelepah sebagai hijauan, dan 19 juta ekor sapi dengan menggunakan solid sebagai bahan tambahan pakan ternak sapi. Model ISSE yang dikembangkan oleh PPKS membuktikan bahwa pemanfaatan sumberdaya industri perkebunan kelapa sawit dapat digunakan sebagai pakan untuk peternakan sapi. 

Spermidine/Spermine N1-Acetyltransferase 1 (SAT1)—A Potential Gene Target for Selective Sensitization of Glioblastoma Cells Using an Ionizable Lipid Nanoparticle to Deliver siRNA

Spermidine/spermine N1-acetyltransferase 1 (SAT1) responsible for cell polyamine catabolism is overexpressed in glioblastoma multiforme (GB). Its role in tumor survival and promoting resistance towards radiation therapy has made it an interesting target for therapy. In this study, we prepared a lipid nanoparticle-based siRNA delivery system (LNP-siSAT1) to selectively knockdown (KD) SAT1 enzyme in a human glioblastoma cell line. The LNP-siSAT1 containing ionizable DODAP lipid was prepared following a microfluidics mixing method and the resulting nanoparticles had a hydrodynamic size of around 80 nm and a neutral surface charge. The LNP-siSAT1 effectively knocked down the SAT1 expression in U251, LN229, and 42MGBA GB cells, and other brain-relevant endothelial (hCMEC/D3), astrocyte (HA) and macrophage (ANA-1) cells at the mRNA and protein levels. SAT1 KD in U251 cells resulted in a 40% loss in cell viability. Furthermore, SAT1 KD in U251, LN229 and 42MGBA cells sensitized them towards radiation and chemotherapy treatments. In contrast, despite similar SAT1 KD in other brain-relevant cells no significant effect on cytotoxic response, either alone or in combination, was observed. A major roadblock for brain therapeutics is their ability to cross the highly restrictive blood–brain barrier (BBB) presented by the brain microcapillary endothelial cells. Here, we used the BBB circumventing approach to enhance the delivery of LNP-siSAT1 across a BBB cell culture model. A cadherin binding peptide (ADTC5) was used to transiently open the BBB tight junctions to promote paracellular diffusion of LNP-siSAT1. These results suggest LNP-siSAT1 may provide a safe and effective method for reducing SAT1 and sensitizing GB cells to radiation and chemotherapeutic agents

Validation of Cadherin HAV6 Peptide in the Transient Modulation of the Blood-Brain Barrier for the Treatment of Brain Tumors

This work is licensed under a Creative Commons Attribution 4.0 International License.The blood-brain barrier (BBB) poses a major obstacle by preventing potential therapeutic agents from reaching their intended brain targets at sufficient concentrations. While transient disruption of the BBB has been used to enhance chemotherapeutic efficacy in treating brain tumors, limitations in terms of magnitude and duration of BBB disruption exist. In the present study, the preliminary safety and efficacy profile of HAV6, a peptide that binds to the external domains of cadherin, to transiently open the BBB and improve the delivery of a therapeutic agent, was evaluated in a murine brain tumor model. Transient opening of the BBB in response to HAV6 peptide administration was quantitatively characterized using both a gadolinium magnetic resonance imaging (MRI) contrast agent and adenanthin (Ade), the intended therapeutic agent. The effects of HAV6 peptide on BBB integrity and the efficacy of concurrent administration of HAV6 peptide and the small molecule inhibitor, Ade, in the growth and progression of an orthotopic medulloblastoma mouse model using human D425 tumor cells was examined. Systemic administration of HAV6 peptide caused transient, reversible disruption of BBB in mice. Increases in BBB permeability produced by HAV6 were rapid in onset and observed in all regions of the brain examined. Concurrent administration of HAV6 peptide with Ade, a BBB impermeable inhibitor of Peroxiredoxin-1, caused reduced tumor growth and increased survival in mice bearing medulloblastoma. The rapid onset and transient nature of the BBB modulation produced with the HAV6 peptide along with its uniform disruption and biocompatibility is well-suited for CNS drug delivery applications, especially in the treatment of brain tumors

SUMBERDAYA INDUSTRI KELAPA SAWIT DALAM MENDUKUNG SWASEMBADA DAGING SAPI NASIONAL

Indonesia masih belum mampu swasembada daging sapi hingga saat ini. Untuk mengembangkan peternakan sapi, ketersediaan pakan dan lahan menjadi faktor pembatas.  Sementara itu industri perkebunan kelapa sawit mempunyai potensi untuk menyediakan pakan sapi. Biomassa dari industri perkebunan kelapa sawit yang dapat digunakan sebagai pakan ternak sapi adalah tanaman hijauan pada kebun kelapa sawit, daun dan pelepah hasil kegiatan panen, dan BIS dan solid dari kegiatan pengolahan kelapa sawit. Berdasarkan perhitungan dan assumsi, industri kelapa sawit Indonesia mampu menyediakan pakan sapi bagi 25 juta ekor dengan menggunakan daun dan pelepah sebagai hijauan, dan 19 juta ekor sapi dengan menggunakan solid sebagai bahan tambahan pakan ternak sapi. Model ISSE yang dikembangkan oleh PPKS membuktikan bahwa pemanfaatan sumberdaya industri perkebunan kelapa sawit dapat digunakan sebagai pakan untuk peternakan sapi.