Nanoparticle design for hydrophilic drugs: Isoniazid biopolymeric nanostructure

Isoniazid (ISN) is a drug used in the treatment of tuberculosis with high hydrophilicity and low molecular weight. Polymeric nanoparticles (PNs) have emerged as a promising approach to overcoming the problems associated with the treatment of tuberculosis. Studies report that the encapsulation of hydrophilic drugs in PNs is a challenge, due to the propensity to leach from the internal aqueous phase to the external aqueous phase. The objective of the study is to develop and characterize dl-lactide/Glycolide copolymer (PLGA) PNs coated with chitosan (CHI) and ISN encapsulation, guided by molecular dynamics and evaluation of factors that interfere with encapsulation efficiency (EE) and drug loading (DL) for hydrophilic drug. By molecular dynamics it was possible to predict that the polymer and drug system is able to reach equilibrium, stability and structural compactness. The electrostatic potential map showed that PLGA, CHI and ISN are able to interact through electrostatic interactions. The chemical bonds that prevail between the polymers and the drug are van der Waals interactions and hydrogen bonds. PNs were optimized using 24−1 fractional factorial design. EE (23.3%) and DL (5.66%) were predicted by the study of molecular dynamics, due to the prevalence of electrostatic interactions that are susceptible to disassociation for the aqueous phase, however molecules that perform hydrogen bonding favor EE and DL. The PNs showed a spherical shape with a dense coating, sustained release and cell viability against A549 cells. The developed PNs are a promising candidate for tuberculosis treatment for pulmonary administration. [Display omitted] •Prediction of formation of nanostructured systems through molecular dynamics.•Encapsulation efficiency and drug loading by hydrogen bonding.•Polymeric nanoparticles with spherical shape and dense particle surface coating.•Chitosan-coated PLGA-isoniazid nanoparticles have cell viability against A549 cells.