Mechanical properties of drug loaded diblock copolymer bilayers: A molecular dynamics study

Abstract

In this work, we present results of coarse-grained simulations to study the encapsulation of prilocaine (PLC), both neutral and protonated, on copolymer bilayers through molecular dynamics simulations. Using a previously validated membrane model, we have simulated loaded bilayers at different drug concentrations and at low (protonated PLC) and high (neutral PLC) pH levels. We have characterized key structural parameters of the loaded bilayers in order to understand the effects of encapsulation of PLC on the bilayer structure and mechanical properties. Neutral PLC was encapsulated in the hydrophobic region leading to a thickness increase, while the protonated species partitioned between the water phase and the poly(ethylene oxide)-poly(butadiene) (PBD) interface, relaxing the PBD region and leading to a decrease in the thickness. The tangential pressures of the studied systems were calculated, and their components were decomposed in order to gain insights on their compensation. In all cases, it is observed that the loading of the membrane does not significantly decrease the stability of the bilayer, indicating that the system could be used for drug delivery.

Study of the Lamellar and Micellar Phases of Pluronic F127: A Molecular Dynamics Approach

“…This characteristic could influence drug partition in PL F127-based nanocarriers. Besides, this interface could also change with the pH, depending on a drug ionization state [13,37].…”

“…For spherical systems, we used the method developed by Nakamura et al [36] and for lamellas, we divided the systems in slabs along the z-direction (similarly to the MDPs) and computed tangential pressure (PT)(z) and normal pressure (PN)(z) for each slab. Details of the calculation method for PT(z) and PN(z) can be found elsewhere [37][38][39]. The calculation of the pressure profiles for both planar and spherical systems was implemented in GROMACS 2018 and its freely available at https://gitlab.com/damgrillo/gromacs-lpressure; it will be further discussed in a future publication.…”

Mechanistic Understanding From Molecular Dynamics Simulation in Pharmaceutical Research 1: Drug Delivery

“…In most cases the drugs being considered are hydrophobic and sit within a non-polar region. Nanoparticles that have been simulated carrying their drug payload include carbon nanotubes, nanographene, peptide carriers, PAMAM dendrimers, polymeric nanoparticles, polymeric micelles, hydrophobic drugs within the membrane of liposomes, other issues related to drug loading of liposomes (Cern et al, 2014) and polymersomes (Grillo et al, 2018) (further citations found in Table 4). Drug cargoes studied include cucurbitacin, carmustine, 5-flouracil (Barraza et al, 2015), chacone, picoplatin, porphyrins, ibuprofen, paclitaxel, and albendazole, however, the most popular drug for these model systems is doxorubicin (see Table 4 for citations).…”

“…Once the nanoparticle has reached the cell, surviving the journey through the bloodstream with its payload still contained and intact, there is one final barrier that must be crossed for the drug delivery system to be efficacious: the cell membrane (Wolski et al, 2017a;Kordzadeh et al, 2019;Ghadri et al, 2020) Liposomes (Cern et al, 2014;Dzieciuch et al, 2015) Nanographene (Moradi et al, 2018;Mahdavi et al, 2020;Maleki et al, 2020) PAMAM dendrimers (Kelly et al, 2009;Wen et al, 2014;Barraza et al, 2015;Badalkhani-Khamseh et al, 2017Farmanzadeh and Ghaderi, 2018;Fox et al, 2018) Peptide Carriers (Thota et al, 2016) Polymeric Micelles (Patel et al, 2010a,b;Guo et al, 2012a;Kasomova et al, 2012;Nie et al, 2014;Myint et al, 2016;Shi et al, 2016;Gao et al, 2019;Kacar, 2019;Wu W. et al, 2019) Polymeric Nanoparticles (Shen et al, 2017;Yahyaei et al, 2017;Ghitman et al, 2019;Styliari et al, 2020) Polymersomes (Grillo et al, 2018) Cargo Molecules: 5-flouracil (Barraza et al, 2015) Albendazole (da Silva Costa et al, 2020) Carmustine (Wolski et al, 2017a) Chacone (Badalkhani-Khamseh et al, 2019) Cucurbitacin (Patel et al, 2010a) Doxorubicin (Yang et al, 2012;Nie et al, 2013;Kordzadeh et al, 2019;Koochaki et al, 2020;…”

Mucus-penetrating polymersomes as a potential lung drug delivery system: preparation, in vitro characterization, and biodistribution tests

“…A key question when using a drug carrier is to understand the loading capacity of the carrier and if the active ingredient affects its stability, especially when dealing with a self-assembled structure. 89 To achieve the information regarding encapsulation efficiency, Men et al 86 between encapsulated and released CAT-1. 90 As a control, we found that DPPC liposomes (1 mg.mL -1 ) could encapsulate 0.53%.…”