An experimental framework for manufacturing nanomedicine via custom-made 3D-printed microfluidics

Khorshid, Shiva

Nanoparticles offer a paradigm shift in therapeutic strategies. These structures, derived from diverse materials, exhibit unique properties such as enhanced drug delivery, controlled release, and targeted therapies. Microfluidic methods, a cutting-edge technology, revolutionize the fabrication of nanoparticles by enabling precise manipulation of fluids in microchannels. This approach provides advantages like scalable production, rapid mixing, and controlled physicochemical properties. Together, nanoparticles and microfluidics redefine therapeutic approaches. For instance, the collaboration has been exemplified in the production of lipid nanoparticles encapsulating mRNA vaccines for cancer and COVID-19, showcasing a transformative leap in the field of medicine. This convergence of nanotechnology and microfluidics holds immense promise for tailored and efficient drug delivery systems, maximizing treatment efficacy while minimizing side effects. In this thesis, the result of the conducted research on nanoparticle preparation utilizing the microfluidic method and Design of Experiments (DoE) during my PhD program has been presented. Initial projects delve into the investigation of novel applications in anticancer drug delivery. Leveraging carbohydrate targeting and the unique properties of berberine, innovative liposomal formulations demonstrate enhanced anti-proliferative effects. In addressing cutaneous mycoses, the thesis introduces keratin nanoparticles as a promising antifungal drug carrier. Tannic acid (TA) crosslinking proves superior to conventional crosslinkers, ensuring stability and effectiveness in tioconazole-loaded keratin nanoparticles (TCZ-KNP). The study exemplifies a tailored approach to combat topical fungal infections. Our third study aims to assess the impact of various nanomedicines on hematological malignancies (HM), offering new possibilities for enhanced patient outcomes, where curative treatments are scarce. Conventional top-down nanomedicine development methods in preclinical research are time-consuming, motivating a bottom-up microfluidic and DoE approach to expedite production, evaluation, and prediction of a nanoparticle (NP) library composed of liposomes, lipid nanoparticles (LNP), and nanoemulsions (NE). Notably, the formulations exhibited considerable uptake without showing any toxicity. In conclusion, this thesis advances nanomedicine by bridging diverse applications through the exploration of NP synthesis methods. The fusion of microfluidics, DoE, and targeted formulations not only showcases a comprehensive and forward-looking approach to revolutionizing therapeutic interventions across multiple medical domains but also offers scalability. This scalability facilitates the transition of nanomedicine from bench to bedside, paving the way for efficient and personalized clinical application

Nanoparticles offer a paradigm shift in therapeutic strategies. These structures, derived from diverse materials, exhibit unique properties such as enhanced drug delivery, controlled release, and targeted therapies. Microfluidic methods, a cutting-edge technology, revolutionize the fabrication of nanoparticles by enabling precise manipulation of fluids in microchannels. This approach provides advantages like scalable production, rapid mixing, and controlled physicochemical properties. Together, nanoparticles and microfluidics redefine therapeutic approaches. For instance, the collaboration has been exemplified in the production of lipid nanoparticles encapsulating mRNA vaccines for cancer and COVID-19, showcasing a transformative leap in the field of medicine. This convergence of nanotechnology and microfluidics holds immense promise for tailored and efficient drug delivery systems, maximizing treatment efficacy while minimizing side effects. In this thesis, the result of the conducted research on nanoparticle preparation utilizing the microfluidic method and Design of Experiments (DoE) during my PhD program has been presented. Initial projects delve into the investigation of novel applications in anticancer drug delivery. Leveraging carbohydrate targeting and the unique properties of berberine, innovative liposomal formulations demonstrate enhanced anti-proliferative effects. In addressing cutaneous mycoses, the thesis introduces keratin nanoparticles as a promising antifungal drug carrier. Tannic acid (TA) crosslinking proves superior to conventional crosslinkers, ensuring stability and effectiveness in tioconazole-loaded keratin nanoparticles (TCZ-KNP). The study exemplifies a tailored approach to combat topical fungal infections. Our third study aims to assess the impact of various nanomedicines on hematological malignancies (HM), offering new possibilities for enhanced patient outcomes, where curative treatments are scarce. Conventional top-down nanomedicine development methods in preclinical research are time-consuming, motivating a bottom-up microfluidic and DoE approach to expedite production, evaluation, and prediction of a nanoparticle (NP) library composed of liposomes, lipid nanoparticles (LNP), and nanoemulsions (NE). Notably, the formulations exhibited considerable uptake without showing any toxicity. In conclusion, this thesis advances nanomedicine by bridging diverse applications through the exploration of NP synthesis methods. The fusion of microfluidics, DoE, and targeted formulations not only showcases a comprehensive and forward-looking approach to revolutionizing therapeutic interventions across multiple medical domains but also offers scalability. This scalability facilitates the transition of nanomedicine from bench to bedside, paving the way for efficient and personalized clinical application.