(25f) Multi-Scale Modeling of Soft Matters: A Quality By Design of Drug Delivery Carriers By a Computational Tool

In this work we investigate computationally the relationship between transient motion of multi-compartment microcapsules and their mechanical properties by flowing them in a microfluidic device. Different active ingredients can be encapsulated separately in inner (daughter) capsules that are surrounded by a larger (mother) capsule. The capsule shell (membrane) can be fabricated with materials that are stimuli (e.g. pH, temperature) responsive. Despite significant experimental advance in the fabrication of multi-compartment capsules [1-4], their deformation mechanisms and rheological behavior are poorly understood. Multi-scale modeling is a tool that facilitates the quality by design (QBD) for the fabrication of pharmaceutical capsules (e.g. Chitosan–alginate microcapsules [5]). QBD of microcapsules increases the probability in targeted delivery and the release of encapsulated materials at desired time and location, and mitigates the risk of cross-contamination between the ingredients. Here, we present the effects of different physical and geometrical parameters such as viscosity ratio, number of inner capsules, their sizes and arrangements on the overall dynamical behavior of multi-compartment capsules, by utilizing our membrane spectral boundary element method [6-9]. We further establish the link between the mechanical properties of these capsules and their deformational behavior, which leads to enhanced manufacturing of these class of drug carriers.

[1] Kim, Shin-Hyun, et al. "Multiple polymersomes for programmed release of multiple components." Journal of the American Chemical Society 133.38 (2011): 15165-15171.

[2] Adams, L. L. A., et al. "Single step emulsification for the generation of multi-component double emulsions." Soft Matter 8.41 (2012): 10719-10724.

[3] Dams, Stanley S., and Ian M. Walker. "[5] Multiple emulsions as targetable delivery systems." Methods in enzymology. Vol. 149. Academic Press, 1987. 51-64.

[4] Vasiljevic, Dragana, et al. "An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier." International journal of pharmaceutics 309.1-2 (2006): 171-177.

[5] Ghaffarian, Rasa, et al. "Chitosan–Alginate Microcapsules Provide Gastric Protection and Intestinal Release of ICAM‐1‐Targeting Nanocarriers, Enabling GI Targeting In Vivo." Advanced functional materials 26.20 (2016): 3382-3393.

[6] Dodson, W. R., and P. Dimitrakopoulos. "Dynamics of strain-hardening and strain-softening capsules in strong planar extensional flows via an interfacial spectral boundary element algorithm for elastic membranes." Journal of fluid mechanics 641 (2009): 263-296.

[7] Koolivand, A., and P. Dimitrakopoulos. "Deformation of an elastic capsule in a microfluidic T-junction: settling shape and moduli determination." Microfluidics and Nanofluidics 21.5 (2017): 89.

[8] Koolivand, Abdollah, and Panagiotis Dimitrakopoulos. "Dynamics of Elastic Multi-Compartment Capsules in Microfluidic Channels." 2019 AIChE Annual Meeting. AIChE, 2019.

[9] Koolivand, Abdollah, and Panagiotis Dimitrakopoulos. "An Advanced 3D Computational Model for Designing Next Generation Drug Carriers." 2019 AIChE Annual Meeting. AIChE, 2019.