Porous Functionalized Calcium Carbonate Microparticle as a Drug Carrier: Pore-scale structure and its role in drug delivery

Porous materials are ubiquitous in nature and technology. The expansive applications of porous materials has brought forth a need for further research on these structures for different purposes. The field of drug delivery is no exception. Porous materials exhibit large surface areas and voluminous void spaces that make them suitable for drug delivery purposes. The drug can adsorb on the pore walls or precipitate inside the pores of these carriers. Functionalized calcium carbonate (FCC) is a porous microparticulate material that has shown great promise for drug delivery applications by incorporating active compounds in its porous meshwork. To be able to fully utilize the benefits offered by the porous structure, the payload must be effectively loaded in the internal structure of the carriers. However, without a clear understanding of the porous structure of the carriers, we are bound to take a black-box approach towards drug delivery with porous materials. This approach poses limitations in terms of design, modification and trouble-shooting of the resulting drug delivery systems. This thesis thus attempted to shed light on the structural characteristics of FCC as a porous material and a drug delivery carrier. Accordingly, we revealed the internal structure of FCC, for the first time, by a direct imaging technique. We proceeded to use this method to investigate the distribution of two model compounds in FCC after loading, and the factors determining this material distribution. The investigation of material loading in FCC were followed by a narrative review on the general kinetics of loading and release from porous media. The acquired knowledge on FCC as a drug carrier was then employed to design a formulation strategy for delivery of liposomes by the oral route. The obtained formulation was a combination of FCC and phospholipids and with the help of the porous structure properties of FCC, lead to a mass formation of liposomes in simulated gastrointestinal media. The thesis was concluded by an attempt to pave the path towards modeling and simulation of mass transport processes involved in drug delivery with FCC. For this purpose, a pore-network model was developed based on tomography images of FCC with a pore-scale resolution. The pore network contained properties of the porous structure, extracted from the direct images of FCC that can be used for modeling the processes of drug loading, precipitation and release in the carrier. The outcome of this thesis contributes to a deeper understanding of drug delivery with FCC and the structural factors influencing the drug delivery behavior in this carrier. The findings from the combination FCC-phospholipid formulations can be used as a platform for formulating oral liposomes and for transforming lipid-based formulations into a dry powder form by loading in FCC.