Structural changes on polymeric nanoparticles induced by hydrophobic drug entrapment

Several scattering techniques (DLS, SLS, SAXS) and transmission electron microscopy (TEM, cryo-TEM) were used to probe how the entrapment of a hydrophobic drug molecule modifies the inner structure of polyester nanoparticles. [Display omitted] The potential use of polyester polymeric nanoparticles (NPs) as drug nanocarriers is well-documented. Nevertheless, structural changes due to hydrophobic drug loading and release have been rarely explored. Herein, we have used static and dynamic light scattering (SDLS), small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM) and cryo-TEM to probe how the entrapment of a hydrophobic drug molecule changes the nanoparticles feature. The presence of the hydrophobic drug molecule modifies the inner structure of the NPs. The polymeric assemblies are characterized by differences in their densities (∼0.06gcm-3 for poly(D,L-lactide) – PLA or poly(D,L-lactide-co-glycolide – PLGA) and 0.46gcm-3 for poly[(butylene succinate)-co-(butylene dilinoleate)] − PBSBDL). They are thus water swollen in the drug-free condition. The NPs were further prepared by using the same polyesters and given amounts of the poorly water-soluble drug paclitaxel (PTX). The density (dNP), RG (radius of gyration), RH (hydrodynamic radius), RG/RH and R (contrast radius) have been monitored as a function of the amount of drug loaded. The drug entrapment increased the size of PLA and PLGA NPs. On the other hand, it also promoted the shrinkage of PBSBDL NPs. These observations revealed that changes in the inner structure of soft nanoparticles caused by drug loading is not straightforward and it mainly depends on the strength of van der Waals interactions between the polyester core and the probe which is connected to their chemical composition and hydrophobicity. These findings are crucial to understand the key physicochemical parameters involved in the interactions between drug and polymer that affects the final particle structure and influence its loading, release and degradation.