Browsing by Subject "hallittu vapautuminen"

Crohn's disease is a type of inflammatory bowel disease. There are no treatment procedures that can cure Crohn's disease, but it is usually controllable with medicinal options. However 70 - 80 % of patients will require surgery and most undergo several during their life, due to weak local potency of drugs and disrupted recovery from surgical treatment. A better method of combined treatment, such as a drug releasing surgical suture, could improve the disease recovery process. One approach would be to coat a surgical suture with nanofibrillar cellulose (NFC) hydrogel containing the active drug ingredient within. NFC is biocompatible, biostable and it can be easily chemically modified. It displays pseudoplastic and thixotropic gel-like behavior in aqueous suspension in addition to high shear thinning properties under low and high shear rates. The shear-thinning behavior is particularly useful in a range of different coating applications. Furthermore, recent studies have shown the potential of NFC in controlled drug release. The aim of this Master's thesis was to investigate the suitability of anionic NFC hydrogel for surgical suture coatings and controlled release applications. The structure of NFC hydrogel was modified with crosslinking cations (Fe3+, Al3+, Ca2+) and alginate. The diffusion studies were performed with two antibiotics, metronidazole and rifaximin together with FITC-dextrans (10 and 250 kDa). The surgical suture was coated with each type of hydrogels (n = 16). Furthermore, the suitability of suture drug formulation for controlled drug release was simulated with STELLA® modeling software. It was shown that the NFC hydrogel structure was stiffened with the use of crosslinking cations; however similar results were not observed with the addition of alginate. Release profiles of model compounds were similar before and after NFC hydrogel crosslinking. At 6 days, 50 - 60 % of 10 kDa dextran (6 µg) was released. For 250 kDa dextran (6 µg) the released amount was 25 - 35 %. During the first 3 days of the diffusion study, all of metronidazole (20 µg) was released. Rifaximin samples were not obtained due to high adsorption to the container surfaces. The release profiles of metronidazole and 10 kDa dextran had linear correlation with square-root diffusion process. 250 kDa dextran followed a near zero-order kinetics after a few hours from the start. The coating was performed successfully with NFC hydrogels except for hydrogels with dextrans or without crosslinking. Metronidazole was predicted to release from the surgical suture almost instantly with STELLA® modeling software. NFC hydrogel shows potential as a matrix for controlled drug release and the coating of surgical sutures. However, the manufacturing method of the NFC hydrogel could be improved with surface modifications of nanofibrils or with the choice of a drug or of its derivatives. With pharmacokinetic simulation models it is possible to predict and estimate different factors which affect drug release from the surgical suture. Furthermore, the simulation models can be used to estimate an effect in the treatment of Crohn's disease.

Cellulose has already been used as an industrial raw material for over a century. However, during recent years the nanostructural features of the naturally occurring biopolymer have been fully investigated and characterized through different processing methods as nanofibrillar cellulose (NFC). This has led to a rapid development of novel cellulose based nanoscale materials and advancements in the field of composite materials. NFC offers interesting specific properties that differ from many other natural and synthetic polymers, such as self-renewable raw materials, semi-crystalline morphology, broad chemical modification capacity, biocompatibility and biodegradability. Biocompatibility and the biomimetic aspects of NFC have enabled the fabrication of nanoporous membranes and scaffolds that can function as medical devices (e.g. tissue engineering, wound healing, novel active implants). In this study, the properties of plant-derived NFC, as potential injectable drug releasing hydrogel "implants" were investigated. Three different sized candidate molecules were selected (123I-NaI, 123I-β-CIT and 99mTc-HSA, from small to large respectively) and investigated with the use of a small animal SPECT/CT molecular imaging device. Study compounds were mixed with the NFC biomaterial and injected into the pelvic region of mice. Drug release was observed for a period of 24 hours and the results were compared to saline/study compound control injections. In addition, 99mTc labeled NFC hydrogels were prepared for dual label tracing to observe the hydrogel positioning during the SPECT/CT acquisitions. For the smaller compounds (123I-NaI, 123I-β-CIT), no differences were found in the drug release or absorption in between the NFC biomaterial and saline injections. However, a clear difference was found with the large compound (99mTc-HSA). In the NFC hydrogel, the rate of release was slower and the distribution of 99mTc-HSA was more concentrated around the area of injection. In addition, the NFC hydrogel did not migrate from, or disintegrate, at the site of injection, suggesting a robust enough structural integrity to withstand normal movement and activity. In conclusion, the labeling of NFC was found to be a reliable and simple method. NFC hydrogels have the potential use as drug releasing medical devices with larger compounds. NFC matrix did not have any controlled release effect on the studied small molecules. Therefore further studies are required for more specific conclusions.