Offre de Postdoc : Drug Release from Capsules Induced by Acoustic Stimulation: A numerical study

Project title : Drug Release from Capsules Induced by Acoustic Stimulation: A numerical study

Research group: Inter­ac­tions Flu­ides Struc­tures Biologiques (IFSB)

Key words: Mul­ti­physics sim­u­la­tions, Drug deliv­ery, Cap­sules
Research work: Cap­sules are closed mem­branes made of poly­mers pro­tect­ing a flu­id droplet. They are increas­ing­ly used in cos­met­ics and phar­ma­ceu­tics to encap­su­late active agents in order to accom­plish con­trolled and tar­get­ed deliv­ery. For exam­ple, in med­i­cine, they are used to trans­port and release drugs or con­trast agents to tar­get­ed sites with­in the human body. The deliv­ery takes place either by mass trans­fer through the cap­sule mem­brane or by com­plete break-up of the entire cap­sule. Mass trans­fer from unbro­ken cap­sules have been exten­sive­ly stud­ied numer­i­cal­ly at BMBI [1–7] as well as the evo­lu­tion of dam­age and ini­ti­a­tion of rup­ture on the mem­brane [8–10]. Exper­i­men­tal study of breakup has shown the fast release of the entire cap­sule car­go [11]. Trig­ger­ing drug release from micro­cap­sules ensures a con­trolled local­ized deliv­ery of the active sub­stances. Among all the pos­si­ble trig­ger­ing strate­gies, ultra­son­ic stim­u­la­tion offers the advan­tages to be con­trol­lable at dis­tance and not dam­ag­ing for the sur­round­ing cells.

The present project aims at mod­el­ing the son­i­ca­tion of micro­cap­sules sus­pend­ed in an exter­nal flow numer­i­cal­ly, and account­ing for the rup­ture of the cap­sule mem­brane when sub­ject­ed to strong ultra­son­ic forces. The recruit­ed per­son will par­tic­i­pate in devel­op­ing a new numer­i­cal method to mod­el the rup­ture of the cap­sule mem­brane using physics-based approach­es. The cap­sule will be mod­eled as a closed spring net­work, as done in Ref. [1], and the mech­a­nism of brit­tle mate­ri­als break-up will be imple­ment­ed. The devel­oped numer­i­cal method will be used to study cap­sule rup­ture as a func­tion of the mem­brane elas­tic prop­er­ties and the strengths of the applied ultra­son­ic stim­u­la­tion and flow. Reg­u­lar com­par­i­son of the the­o­ret­i­cal and numer­i­cal results will be done to exper­i­men­tal results obtained by oth­er part­ners of the ANR project to improve the mod­els and help explain the observed phe­nom­e­na.

Planned tasks and deliv­er­ies of the project:
Learn­ing the fun­da­men­tals of the lat­tice Boltz­mann method (LBM) and get famil­iar with the in-house com­put­er code “lbm3d”, design and imple­men­ta­tion of bound­ary con­di­tions need­ed to com­pute flow induced by ultra­sound, per­form val­i­da­tion, con­ver­gence tests and bench­mark­ing tests of the new­ly devel­oped code that mod­els ultra­son­ic forces.

Learn­ing the fun­da­men­tals of the finite ele­ment method (FEM) need­ed to com­pute the mechan­ics of the cap­sule, and the immersed bound­ary method (IBM), need­ed to accom­plish the flu­id-struc­ture inter­ac­tion (FSI) with the Caps3D code [12], get famil­iar with both in house com­put­er codes “Caps3D” and “ibmd3d”, cou­pling the struc­ture with the ultra­sound-flow solver, per­form sys­tem­at­ic numer­i­cal study of the dynam­ics and defor­ma­tion of the cap­sule under ultra­son­ic forces, com­par­i­son with exper­i­men­tal results,
Study the cap­sule break-up event and the accom­pa­nied release of the cap­sule car­go, study the spa­tial dis­tri­b­u­tion of the released mol­e­cules with­in blood ves­sel, and its absorp­tion rate by the ves­sel wall and sur­round­ing tissues.