Genetic and cellular therapies represent a group of new techniques based on overlapping fields of biomedical research with similar goals. A new approach in this domain is represented by the development of different personalized gene therapies for patients with rare diseases. There are more than 6000 rare disorders, each with low frequency in the population (less than 5 people in 10,000). The first approved clinical protocol to introduce foreign DNA into humans has been reported by S.A. Rosenberg et al. in the last decade of the previous century. Nontheless, R. Maldonado et al. has recently reported in an extended review that this research field needs collaborative efforts from multidisciplinary teams. Evemore they consider that this kind of therapy has the potential for curative treatment in rare genetic conditions.
The targeted and controlled release of different active bio-molecules is probably the main parameter of a drug delivery system. Drug carriers are developed to protect the loaded agent and / or to modify its properties such as the aqueous solubility and bioavailability. Inorganic, organic and molecular compounds with different shapes such as carbon nanotubes, gold nanorods and nanoparticles and polymer nanocapsules and dendrimers have been developed as drug carriers in the last three decades. Polyurethanes (PU) are versatile biocompatible materials with many applications, such as flexible or rigid foams, artificial skin for the premature neonate, membrane in hybrid artificial pancreas, prosthetic heart valves, etc.
Molecular dynamics-based investigations on the chemical structures of new compounds represent modern, cheap and safe tools that help in understanding structure-property approaches. Different molecular descriptors, such as hydrophobicity descriptors, refractivity descriptors, that are used in computer-aided drug discovery and chemoinformatics, are often used to predict the effect of molecular properties (hydrogen bond donor/acceptor, hydrophobic, steric and electrostatic properties in different 3D-QSAR models. Human pharmacokinetics is of great significance in the selection of drug candidates, and in silico estimation of pharmacokinetic parameters in the field of drug delivery systems is based on docking investigations.
Molecular structures of a series of polyether-urethane capsules and dendrimers have been designed using Bioavia Draw 2019 software; isophorone-diisocyanate and hexamethylene-diisocyanate were used as aliphatic compounds of organic phase, while mixtures of polyethylene-glycol and 1,4-butandiol were used as the main components of the aqueous phase. The geometry of all obtained structures has been optimized using the computational methods AMBER and MM+ from Hyper Chem 8.0. The main structural parameters such as polarizability, refractivity, logP, various energies, solvent-accessible area, van der Waals area, solvent-accessible volume and van der Waals volume) were calculated. The interaction between the polymer matrix and the genetic material have been analysed by PyRX, a virtual screening tool, which is an open-source software with an intuitive user interface that runs on all major operating systems.
Our results indicate that the dendritic polyether-urethane particles represent a more proper carrier for a fast release of the genetic material, while the capsules present a constant concentration for a prolonged release.