ABSTRACT
Additive manufacturing (AM) techniques and so-called 2D materials have undergone an explosive growth in the past decade. The former opens multiple possibilities in the manufacturing of multifunctional complex structures, and the latter on a wide range of applications from energy to water purification. Extrusion-based 3D printing, also known as Direct Ink Writing (DIW), robocasting, and often simply 3D printing, provides a unique approach to introduce advanced and high-added-value materials with limited availability into lab-scale manufacturing. On the other hand, 2D colloids of graphene oxide (GO) exhibit a fascinating rheology and can aid the processing of different materials to develop 'printable' formulations. This work provides an in-depth rheological study of GO suspensions with a wide range of behaviours from Newtonian-like to viscoelastic 'printable' soft solids. The combination of extensional and shear rheology reveals the network formation process as GO concentration increases from <0.1 vol% to 3 vol%. Our results also demonstrate that the quantification of 'printability' can be based on three rheology parameters: the stiffness of the network via the storage modulus (G'), the solid-to-liquid transition or flow stress (σf), and the flow transition index, which relates the flow and yield stresses (FTI = σf/σy).
ABSTRACT
HIV is a global public health threat and requires life-long, daily oral dosing to effectively treat. This pill burden often results in poor adherence to the medications. An injectable in situ forming implant with tuneable drug release kinetics would allow patients to replace some of their daily pills with a single infrequent injection. In this work, we investigate how the size of poly(N-isopropylacrylamide) (polyNIPAm) nanogels influences the long-acting release behaviour of the HIV drug lopinavir from an in situ forming implant. Four sizes of polyNIPAm nanogels were prepared with mean diameters of 65, 160, 310 and 450 nm as characterised by dynamic light scattering. These nanogels all displayed synergistic dual stimuli responsive behaviour by aggregating only upon heating above 31 °C at physiological ionic strength. Mixing the nanogels with solid drug nanoparticles (SDNs) of lopinavir and exposing this concentrated dispersion to physiological temperature and ionic strength resulted in the in situ formation of nanocomposite implants. Three different loadings of the SDNs (33, 50 and 66% w/w) with each of the nanogels were prepared. The drug release behaviour and stability of these nanocomposite implants were then assessed in vitro over 360 hours. All samples displayed a single phase of drug release and application of the Ritger-Peppas equation indicated Fickian diffusion. Nanocomposites with the lowest loading of SDNs (33%) showed a linear relationship between nanogel diameter and the dissolution constant. These results show an attractive method for tuning the release of lopinavir from in situ loading implants with high drug loadings.
