Atomistic Simulations for Construction of an “in Vitro - In Vivo - Ex Vivo – in Cyto - in silico” Performance-Correlation Profile within Biomedical Material Assemblies

In silico static-lattice atomistic simulations (SLAS) and molecular mechanics energy relationships (MMER), in vacuum and solvent phase, have been employed by our research group to quantify and correlate the “in vitro - in vivo - ex vivo – in cyto” performance of various drug delivery systems and tissue engineering scaffolds. The reactional profiles of multicomponent biomedical material assemblies, polymeric combinations, ionic and chemical crosslinkers, enzymatic degradation, mucopeptidic interactions, and stimuli-responsive systems were elucidated by exploring the spatial disposition of the molecular components. The presentation will focus on the applications of SLAS and MMER in our recently completed and published studies and will discuss:

• nanoformation and solvation properties of the surfactant-emulsified polymeric nanosystems
• stabilizer-interaction displayed considerable stereospecificity, proper spacing and geometry of the coordination shell providing “crosslinking stabilized–stabilized emulsion” systems.
• amphiphilic polymer–peptide aggregation confirmed that passing of a polymer–peptide conjugate through the cell membrane requires a hydrophilic–lipophilic-balance with lipophilicity on the higher side.
• incorporation of a physical crosslinker to a polymer complex lead to the accumulation of cohesion forces among the side-by-side polymer fragments chains, due to intermolecular crosslinking, inducing an axial stress
• energy stabilization, low SVR, high density, lower polarizability and lower refractivity lead to highly efficient interactions within the polyelectrolyte complexes
• plasticizers and crosslinking closely effect the “cohesive energy density (CED)” and hence the mechanical properties of polymeric fibers. The molar volume defines the elastic as well cohesive properties of a polymeric architecture
• catalytic action of enzymes reduces molecular energy by a large quantity through relaxing close interatomic contacts
• protein-polysaccharide and polymer-mucopeptide complexes
• biological mucoglycopeptide–polymer dimerizations impacted the pK profile of drugs as they played a significant role in the retention of the polymeric implant for a longer time in the vaginal tissue with strong binding constants
• electroactive molecules in electroresponsive hydrogels tend to drift close to the hydrogen-bonding sites sunken inside the polymer structure displaying a critical “jump diffusional behaviour”.
• molecular interactions inherent to multicomponent matrix formation and the mucoadhesion mechanism.

To date we have successfully demonstrated and published (≈50 papers) the role of molecular mechanics energy relationships towards the interpretation and understanding of the mechanisms that control the formation, fabrication, selection, design, performance, complexation, interaction, sterospecificity, and preference of various biomaterial systems for biomedical applications.

Key References:

Colloids and Surfaces B: Biointerfaces 87 (2011) 243-254

AAPS PharmSciTech 12 (2011) 227-238

Biofabrication 4 (2012) 025002

Pharmaceutical Research 29 (2012) 3075–3089

Journal of the Mechanical Behavior of Biomedical Materials 23 (2013) 80–102

Journal Pharmaceutical Sciences 102 (2013) 2780–2805

International Journal of Pharmaceutics 448 (2013) 267– 281

Journal of Controlled Release 166 (2013) 234–245

Pharmaceutical Research 31 (2014) 607-634

International Journal of Pharmaceutics 462 (2014) 52–65

Pharmaceutical Research 32 (2015) 2384–2409

Pharmaceutical Research (2016) 33:3057–3071

Carbohydrate Polymers 135 (2016) 324–333

Journal of Drug Delivery Science and Technology 37 (2017) 123-133

Materials Science and Engineering C 78 (2017) 376–388