Controlled Release System for Localized and Sustained Drug Delivery Applications

Current controlled release formulations has many drawbacks such as excess of initial burst release, low drug efficiency, non-degradability of the system and low reproducibility. The present project aims to offer an alternative by developing a technique to prepare uniform, biodegradable particles (~19 µm) that can sustainably release a drug for a specific period of time. Chitosan is a natural polysaccharide that has many characteristics to be used for biomedical applications. In the last two decades, there have been a considerable number of studies affirming that chitosan could be used for pharmaceutical applications. However, chitosan suffers from inherent weaknesses such as low mechanical stability and dissolution of the system in acidic media. In the present study, chitosan microparticles were prepared by emulsification process. The model drug chosen was acetylsalicylic acid as it is a small and challenging molecule. The maximum loading capacity obtained for the microparticles was approximately 96%. The parameters for the preparation of uniform particles with a narrow size distribution were identified in a triangular phase diagram. Moreover, chitosan particles were successfully coated with thin layers of poly lactic-co-glycolic acid (PLGA) and poly lactic acid (PLA). The performance of different layers was tested for in vitro drug release and degradation studies. Additionally, the degradability of the system was evaluated by measuring the weight loss of the system when exposed to enzyme and without enzyme.Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM) and inductively coupled plasma optical emission spectrometry (ICP-OES) were used to characterize the controlled release system. Additionally, the in vitro drug release was monitored by ultraviolet-visible spectrophotometry (UV-Vis) and liquid chromatography mass spectrometry (LC-MS). The results obtained from this project showed that it is possible to prepare biodegradable microparticles with a uniform size distribution and high drug loading efficiency. However, this could only be achieved with a hybrid system consisting of chitosan matrix interior and then exterior coating of PLGA or PLA. A two layer coating of PLGA 50:50 was shown to be optimal with sustainable controlled drug release for almost 5 days and with 91% of degradation (weight loss) in 8 weeks.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biomedical Engineering

Grantor dc:publisher

University of Toledo

Year dc:date

2013

Author dc:creator

• Rodriguez, Lidia Betsabe

Contributors dc:contributor

• Nadarajah, Arunan

• Biomedical Engineering
• Biomedical Research
• Chemical Engineering
• Materials Science
• chitosan
• controlled
• aspirin
• sodium tripolyphosphate
• poly lactic acid
• poly lactic co glycolic acid
• poly glycolic acid
• degradation
• release

Statement dc:rights

• unrestricted
• This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.

Language dc:language

English

Repository record dc:identifier

http://rave.ohiolink.edu/etdc/view?acc_num=toledo1365107103

OAI identifier oai:identifier

oai:etd.ohiolink.edu:toledo1365107103