Diffusion Kinetics for Drug Release and Food Preservation

Abstract

This thesis presents silica nanoparticles for the controlled release of AMACR-conjugated doxorubicin for the inhibition of prostate cancer cell growth. Inorganic MCM-41 silica nanoparticles were synthesized, functionalized with phenylboronic groups (MCM-B), and capped with dextran (MCM-B-D). The nanoparticles were then characterized using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), zeta potential analysis, N2 sorption, X-ray diffraction, and thermogravimetric analysis before exploring their potential for drug loading and controlled drug release. This was done using a model prostate cancer drug, doxorubicin (DOX), and a targeted prostate cancer biomarker to facilitate the localized delivery of the drug, α-Methyl Acyl-CoA racemase (AMACR)-conjugated DOX, which attaches specifically to receptors that are overexpressed on the surfaces of prostate cancer cells. The kinetics of controlled drug release over 30 days was then studied using zeroth order, first order, second order, Higuchi, and the Korsmeyer-Peppas models, while the thermodynamics of drug release was elucidated by determining the entropy and enthalpy changes. The flux of the released DOX was also simulated using the COMSOL Multiphysics software package. Generally, the AMACR-conjugated DOX drug-loaded nanoparticles were more effective than the free DOX drug-loaded formulations in inhibiting the growth of prostate cancer cells (PC-3 cell line) in vitro over a 96-h period. Furthermore, the effectiveness of DOX-A cancer drug for the targeted treatment of prostate cancer was explored in vivo. AMACR-conjugated drug (AMACR-doxorubicin) and free doxorubicin drug injections into groups of 4-week-old athymic male nude mice were discovered to target and shrink tumors without any apparent cytotoxicity, as shown by ex vivo toxicity histopathology studies. Our findings demonstrate that prostate cancer cells/tumors with overexpressed AMACR receptors act as binding sites vi for AMACR-conjugated drugs, which in both in vitro and in vivo tests prevented the growth of prostate cells/tumors. The ability to restrain the growth of prostate cancer cells/tumors effects are due to the adhesive contacts between the overexpressed AMACR receptors on the prostate cancer cells/tumors and the AMACR molecular recognition units on the drug doxorubicin, DOX and DOX-A. The implications of the results are then discussed for the development of drug-eluting structures for the localized and targeted treatment of prostate cancer. The second phase of the work, presents the release kinetics (RK) of a fungicidal antimicrobial agent (AMA), potassium sorbate (PS), that prolongs the shelf life of packaged food. The effects of PS release are explored on peanuts and fresh bread to determine the effects of PS on Aspergillus niger (A. niger) microbial growth. The A. niger was cultured in a potato dextrose agar (PDA) medium to obtain AMA activity on the film. AMA activity of PS incorporated into cellulose acetate (CA) based film was tested on peanuts and fresh bread for an extended period of time. The RK of PS from the films was obtained by studying the de swelling properties of PS loaded film at room temperature (24°C) and at elevated temperature (37°C). The diffusion coefficients of PS released through the film network were obtained to be between 8.32 × 10−10 to 7.3 × 10−7 m2/s. The release exponents (n) of PS from the film occurred by anomalous transport with n values ranging from 0.13 to 0.16 at 24°C and 0.5 to 0.89 at 37°C. The average flux released from the CA film was consistent with the percentage PS release from the CA film showing that modelling the effective diffusion of PS from a porous media is feasible. The released PS was potent enough to inhibit the growth of A. niger for a week then over a period of 2 years. Thereafter, the implications of the results in designing smart food packaging for enhanced food preservation were discussed