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Modeling Of Hydroxycamptothecin Release From Electrospun Fibers

Posted on:2011-06-29Degree:MasterType:Thesis
Country:ChinaCandidate:H T LiaoFull Text:PDF
GTID:2144360305460857Subject:Biochemistry and Molecular Biology
Abstract/Summary:PDF Full Text Request
Hydroxycamptothecin (HCPT) has gained widespread interests for cancer therapy, as it has obvious antitumor effect. However, the low solubility, low photo-stability and high toxicity are the practical limits for clinical applications. Encapsulation of HCPT into biodegradable polymeric carrier can decrease the toxicity, improve the stability, and promote the bioavailability. Many studies have been done on simulation or prediction the release profile of drug delivery system through a series of mathematical models. In present study, HCPT loaded poly(ethylene glycol)-poly (DL-lactic acid) (PELA) nanofibers were prepared by electrospinning, and the release profiles had been simulated by Higuchi, Fick-2 diffusion, and Monte Carlo models. With the obtained parameters, the release profiles of HCPT encapsulated in other kinds of nanofibers can be predicted. Then, the predicted similarity values had been compared with the exact similarity value calculated using the actual dataset.Nanofibers with different average size can be prepared by regulating the concentration of polymer concentration. HCPT-loaded nanofibers prepared by blend electrospinning possessed uniform morphology and high drug loading efficiency. The diameters of nanofibers can be controlled from 800 to 1600 nm. The fiber diameter, drug loading, and polymer composition have some effects on in vitro drug release and polymer degradation. It was indicated that higher drug loading, smaller fiber diameter, and faster polymer degradation led a faster drug release. The decrease of fiber diameter would accelerate the polymer degradation, while the drug loading had little effect on the matrix degradation.According to the structural properties of electrospun fibers, drug release profile of HCPT loaded PELA nanofibers were simulated using the Higuchi model, and the relational expression of drug release percent and the incubation time were obtained. The parameters in this relational expression were determined through fitting with the experimental data. The results indicated that the prediction similarity value of drug release profiles from electrospun fibers with different diameters was higher than that of fibers with different drug loadings.According to the Fick-2 model and the fiber structure, the release profiles of HCPT loaded in PELA and PDLLA electrospun fibers were simulated, neglecting the polymer degradation, and the relational expression of drug release percent and the incubation time were obtained. The parameters in this relational expression were determined through fitting with the actual dataset. It also indicated that the predicted similarity value of drug release profile from electrospun fibers with different diameters was higher than that of fibers with different polymer compositions. The lower predicted similarity value of fibers with matrix polymer of PELA and PDLLA (50/50), by the use of drug diffusion coefficient of PELA and PDLLA, was due to the large differences in the degradation profile between PELA and PDLLA.According to the principle of Monte Carlo and the structural properties of electrospun fibers with different drug loadings and diameters, the nanofibers were divided into numbers of layers and pixels, the drug release were simulated by the Matlab program and fitted with the experimental data, and the constants of Monte Carlo were determined. It indicated that the predict similarity values of fibers with higher drug loading were better than those of lower drug loadings. Besides these, the fibers with different diameters also had excellent predict similarity values of drug release.The aforementioned three models can be used to simulate the drug release from fibers with different characteristics, even though there are some limitations. This study proved that the drug release profile of electrospun fibers could be controlled by regulating the fiber characteristics, and provided some theoretical basis to achieve highly sustainable and controllable drug releasing kinetics for electrospun fibers.
Keywords/Search Tags:Electrospun nanofibers, Hydroxycamptothecin, Drug release modeling, Higuchi model, Fick model, Monte carlo
PDF Full Text Request
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