POTENTIAL OF MICROCRYSTALLINE CELLULOSE-G- POLY(ITACONIC ACID) AS ?-TOCOPHEROL CARRIER MATERIAL
The definition of a drug according to the FDA (Food and Drug Administration) is a substance used for the mitigation, treatment, and therapy of a disease. In increasing the effectiveness of treatment, drugs need a carrier to produce a controlled delivery systems. Drug carriers that produce a controll...
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Format: | Theses |
Language: | Indonesia |
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Online Access: | https://digilib.itb.ac.id/gdl/view/75522 |
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Institution: | Institut Teknologi Bandung |
Language: | Indonesia |
Summary: | The definition of a drug according to the FDA (Food and Drug Administration) is a substance used for the mitigation, treatment, and therapy of a disease. In increasing the effectiveness of treatment, drugs need a carrier to produce a controlled delivery systems. Drug carriers that produce a controlled delivery pattern can release the drug in a constant concentration over a long period of time. With this, the drug is used in the long-term and there is no need for repeated drug doses as in conventional drug delivery systems. This study used a microcrystalline cellulose-graft-poly(itaconic acid) (MCC-PIA) and ?-tocopherol drug models were used. The ?-tocopherol used as a model drug in this study has hydrophobic properties so its bioavailability is low. This reduces the effectiveness of ?- tocopherol in the treatment process. Therefore, an ?-tocopherol carrier is needed to increase bioavailability. The backbone of MCC-g-PIA is hydrophilic, while the side chain is hydrophobic. The amphiphilic structure can result in the formation of micelles. In the synthesis of this copolymer, the grafted itaconic acid DPn was varied to 10 and 20. The % grafting values obtained for MCC-g-PIA DPn 10 and 20 were 60.21% and 22.02%. The characterization carried out on MCC-g-PIA was Fourier Transform Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), and Particle Size Analyzer (PSA). The success of copolymer synthesis is proven by the presence of a new peak in the infrared absorption band at 1645 cm-1. That peak indicates the presence of a C=O group of itaconic acid grafted onto the main chain of microcrystalline cellulose. In addition, there was a decrease in the % crystallinity index from 24.27 % for the microcrystalline cellulose chain, to 8.96 % and 10.32 % for MCC-g-PIA DPn 10 and 20. The decrease in % crystallinity index indicated the formation of copolymers due to poly(itaconic acid) chains that disrupt the hydrogen bonds in microcrystalline cellulose thereby reducing the % crystallinity index. The process of carrying ?-tocopherol was carried out by forming micelles with DPn 10 and 20 Critical Micelle Concentration (CMC) values of 50 ppm and 150 ppm. The carrier of ?-tocopherol by MCC-g-PIA can be seen from the enlarged micelle size in the presence of ?-tocopherol from the PSA results. The amount of ?-tocopherol carried by MCC-g-PIA DPn 10 and 20 was 1.74 mg and 0.92 mg, respectively.
The molecular process of carrying ?-tocopherol can also be observed based on the results of molecular dynamics simulations. In the molecular dynamics simulation, the variations of DPn itaconic acid grafted onto microcrystalline cellulose are 1 and 2. Based on the simulation results, the ?-tocopherol carrying process can be carried out at pH 2.97 wich indicated by several observations. The first observation was the presence of two Radial Distribution Function (RDF) peaks of the copolymer towards ?-tocopherol in the range of 0.5 - 0.9 nm. The second observation is a decrease in Solvent Accessible Surface Area (SASA) which indicates the presence of aggregation of copolymer chains that interact with ?- tocopherol. In the third observation regarding the trajectory results, it was found that the number of chains that interacted with ?-tocopherol were two and three for MCC-g-PIA DPn 1 and 2. Analysis of the delivery pattern of ?-tocopherol was carried out in Phosphate Buffer Saline (PBS) with pH 7, 40 and 5.75. In the analysis of the delivery pattern, MCC-g-PIA produced a controlled ?-tocopherol delivery pattern at both pH levels. This is evidenced by the drug release profile with a constant concentration of ?-tocopherol within 150 minutes. Based on experimental and computational results, MCC-g-PIA has the potential as a carrier material for ?-tocopherol which produces a controlled drug delivery pattern.
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