Synthesis of poly(methyl methacrylate-co-methacrylic acid) copolymers and their application in the development of oral and transdermal drug delivery systems

• Author / Creator

  Chakrapani, Harish

• pH-responsive polymers have been intensively investigated over the years due to their diverse applications in environmental decontamination, nutrient delivery/packaging, cosmetics, and pharmaceutical science. A pH-responsive swelling/shrinkage behavior of encapsulation systems can be accounted for by the conformation change of polymer chains at different pH. However, it is unusual to find their commercial applications due to several technical limitations such as incomplete protection of the encapsulated ingredients against harsh environmental conditions, weak response to pH change, and inefficient release behaviour. Previously in our group, macropored microparticles (MPs) have been developed to increase drug loading capacities and protect the drugs from harsh gastric environments using commercially available pH responsive polymers, overcoming major technical challenges for oral drug delivery systems. We wanted to further synthesize copolymers with different material properties such as pKa, (acid dissociation constants) by changing the hydrophobic/hydrophilic ratio of methyl methacrylate to methacrylic acid to better understand the effects of pH responsiveness and their influence on pH responsive drug delivery system to overcome the fixed characteristics of commercially available polymers.
  To this end, we synthesized pH-responsive low molecular weight poly (methyl methacrylate-co-methacrylic acid) copolymer with different acid dissociation constants for better intestinal targeting using free radical solvent copolymerization. We further characterized the copolymers and used them to fabricate MPs with pH-responsive macropores in the development of intestine-targeted oral drug delivery systems. The pH-responding release behaviour of the pored MPs was examined by monitoring time-dependent release profile of encapsulated 100-nm fluorescent nanoparticles in simulated gastrointestinal (GI) tract environment. Further, we encapsulated pH-sensitive drug and measured the remaining activity after subjected to GI tract. Our pH-sensing copolymer and MP delivery system will advance the current microencapsulation technology by solving key challenges in encapsulation, protection, and release of oral drugs and biopharmaceuticals.
  Another important characteristic of these anionic copolymers is their environmental stability. They can be used as protective layers for long-term storage stability as these polymers can protect the drugs from moisture. Microneedles have been researched extensively as an effective drug delivery system for transdermal applications. However, due to low mechanical strength of the conventional based sugar microneedles, it is difficult for them to penetrate the animal skin. Moreover, these sugar-based microneedles are not environmentally stable, failing to protect the drugs from moisture. In this work, we used micromolding techniques to fabricate cellulose nanocrystal-based microneedles of different concentrations and studied the mechanical strength of the microneedles. The microneedles fabricated by cellulose nanocrystals (CNC) and trehalose formulations had almost 6-fold increase in the failure force of the microneedles than the previously fabricated microneedles with CMC and trehalose formulations. Also, we coated these CNC-trehalose based microneedles with the anionic copolymer, i.e. Eudragit S100, by custom designed spray coating device to increase the long-term storage stabilities. Our CNC microneedles will advance the current sugar-based microneedles with higher mechanical strength and greater drug stability and would be the future way of delivering vaccines over conventional needle injections.

• Subjects / Keywords

  • Transdermal drug delivery
  • Microneedles
  • pH sensitive polymers
  • oral drug delivery
  • Microparticles

• Graduation date

  Spring 2020

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/r3-zhe0-j073

• License

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