Development of a Novel Oral Drug Delivery System Using pH-Responsive Hollow Microparticle with Macropores on the Surface

• Author / Creator

  Sun, Chengmeng

• Oral administration of drugs is considered advantageous over all other routes of drug delivery due to several benefits, including painless self-administration, lack of biohazardous waste, and easier and cold-chain free transportation. However, numerous environment sensitive drugs such as vaccines lose their therapeutic efficacy due to the extreme pH environment in the gastrointestinal (GI) tract. Till now, several methods have been proposed to produce microencapsulation systems for oral drug delivery, such as emulsion polymerization and spray drying. However, a universal, efficient, and effective drug delivery system for environment-sensitive biopharmaceuticals is still unavailable. The main drawback of emulsion polymerization method is the exposure of the drug to the organic solvent suspension during the microparticle synthesis process, which commonly causes loss of bioactivity of pharmaceuticals. Similarly, spray drying involves complicated optimization of the fabrication parameters such as temperature, concentrations, and feed rate for different types of drugs. To overcome these technical challenges, we have developed a novel and facile method of producing microparticles with pH-responsive macropores. And since the microparticle fabrication and drug encapsulation steps are independent, the problem of loss of bioactivity of drugs has been addressed. Microparticles were prepared using a FDA approved pH-responsive copolymer poly-(methacrylic acid-co-ethyl acrylate) with a monomer ratio of 1:1. Scanning electron microscopy analysis was used to study morphology and confirm the pore formation. The microparticles were sized ~35 μm in diameter with pores' diameter ranging from 1-10 μm. In a systematic approach, the effects of stirring, temperature, and evaporation time on pore formation were investigated. Following successful encapsulation of model drug (100 nm fluorescent nanoparticles, abbreviated as FNPs) and pH-sensitive drug (pravastatin sodium), the release profiles of ingredients were studied by employing UV-Vis, UV-MS, and fluorescence microscopy to demonstrate our proof-of-concept intestine-targeted drug delivery system. In this work, we found that the encapsulated pravastatin maintained > 60% of its original activity and was released after 6 hours of incubation in simulated GI tract environment which proved that the high effectiveness of our proof-of-concept microparticles drug delivery system.

• Subjects / Keywords

  • microparticle
  • pH-responsive
  • encapsulation

• Graduation date

  Fall 2017

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R35718447

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.