Drug delivery systems to include liposomes and microparticles in order to aid treatment of glioma.
Masters thesis, University of Central Lancashire.
Targeted drug delivery is achieved by enhancing drug availability at the response site while minimising its availability at other sites, especially those that manifest toxicity. The effects of liposomes and polymeric nanoparticles in cancer chemotherapy have been investigated in recent years and there have been some interesting outcomes resulting in improved survival rates of the patients. Thus, the present study was carried out to investigate the effect of encapsulating TMZ and Patrin-2 into liposomes and microparticles separately in order to enhance the delivery.
A validated HPLC system was used for the analysis of both TMZ and Patrin-2. First phase of our study involved the preparation of a delivery system of TMZ and Patrin-2 through liposomes in order to enhance the treatment of glioma. It involved the application of freeze-thaw and dehydration-rehydration methods to encapsulate the TMZ into liposomes. However, the desired encapsulation efficiency (EE %) of TMZ was not achieved using these methods, the maximum entrapment achieved with freeze-thaw method was 11.54 ± 0.70 % while for dehydration-rehydration method was 26.69 ± 0.34 %. Therefore the second phase focussed on preparing polymeric microparticles for continuous delivery of intact TMZ and Patrin-2 using the spray dry method. The maximum entrapment achieved using this method for TMZ was 64.32 ± 2.58 % while the maximum entrapment achieved for Patrin-2 was 68.47 ± 1.47 %, thus, this technique was found to be successful for the preparation of both TMZ and Patrin-2 loaded PLGA microparticles. Furthermore the release study of both TMZ and Patrin-2 was investigated using dispersion and dialysis methods. TMZ and Patrin-2 showed an initial burst release, however TMZ later showed decrease in concentration over the period of time while Patrin-2 showed a slow release with an increase in concentration.
This novel study aids in comparing various methods used for investigating the preparation of TMZ loaded liposomes, and TMZ and Patrin-2 loaded microparticles. In preparation of liposomes based on this research dehydration-rehydration was found to be a more efficient method than the freeze-thaw method for encapsulating TMZ, while the spray dry method was found to be more effective than the emulsifying solvent evaporation method in obtaining the maximum EE % for TMZ and Patrin-2 for preparation of microparticles. The release profiles of TMZ and Patrin-2 from the microparticles was studied using the dispersion method and the dialysis bag diffusion technique however due to tome being the limited factor the technique could not be explored completely.
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