Nanoporous materials have attracted significant attention as drug delivery platforms, in which interfacial phenomena are often more influential than fluid mechanics in defining molecular loading capacity and release kinetics. This study employs nanoporous gold (np-Au) as a model material system to investigate physical mechanisms of molecular release of fluorescein (a small molecule drug surrogate) from the sub-micron-thick np-Au coatings. Specifically, the study reveals an interfacial mechanism where halide ion-gold surface interactions dictate the loading capacity and release kinetics of fluorescein. We systematically study the effect of halide concentration and species on release kinetics from sputter-deposited np-Au films with a combination of quantitative electron microscopy, fluorospectrometry, and electrochemical surface characterization techniques. The results suggest that the interplay of halide-gold interaction probability and affinity determine the nature of release kinetics. The former mechanism plays a more dominant role at higher ionic strengths, while the latter is more important at lower ionic strengths. This interfacial phenomenon is further complemented by functionalizing the np-Au with self-assembled monolayers (SAMs) of alkane-thiols for modulating gold surface-halide affinity and consequently the molecular release kinetics.
Nanoporous gold (np-Au) is a nanostructured metal with many desirable attributes. Despite the growing number of applications of nanoporous materials, there are still open questions regarding their fabrication and subsequent surface functionalization. For example, the hydrophobic nature of gold surfaces makes the formation of planar supported lipid layers challenging. Here, the authors engineer the interface between np-Au and 1,2-dioleoyl-sn-glycero-3-phosphocholine lipid layers using well-differentiated approaches based on vesicle adsorption and solvent exchange methods. The results reveal that the nanotopography of the np-Au surface plays a clear role in the vesicle adsorption process. Compared to vesicle adsorption, the solvent exchange method proves successful in the formation of planar supported lipid bilayers in both np-Au and planar Au surfaces, being less sensitive to the surface morphological features. The influence of nanostructured surfaces on lipid layer formation is determined by the driving mechanisms behind each process, i.e., the balance of adhesion and cohesion forces in vesicle adsorption and lyotropic lipid phase transitions in solvent exchange, respectively. A better understanding of such interactions will contribute to the development of a variety of applications, from electrochemical biosensors to drug screening and delivery systems, using nanoporous gold coated with stimuli-responsive lipid layers.
Surface-molecule interactions play an essential role in loading capacity and release kinetics in nanostructured materials with high surface area-to-volume ratio. Engineering the surfaces via immobilizing functional moieties is therefore a versatile means to enhance the performance of drug delivery platforms with nanostructured components. Nanoporous gold (np-Au), with its high effective surface area, well established gold-thiol chemistry, and tunable pore morphology, is an emerging material not only for drug delivery applications but also as a model system to study the influence of physicochemical surface properties on molecular loading capacity and release kinetics. Here, we functionalize np-Au with self-assembled monolayers (SAMs) of alkanethiols with varying functional groups and chain lengths, and use fluorescein (a small-molecule drug surrogate) to provide insight into the relationship between surface properties and molecular release. The results revealed that electrostatic interactions dominate the loading capacity for short SAMs (two carbons). As SAM length increases the loading capacity displays a nonmonotonic dependence on chain length, where for medium-length SAMs (six carbons) allow for higher loading plausibly due to denser SAM surface packing. For longer SAMs (11 carbons), the steric hindrance due to long chains crowds the pores, thereby hampering fluorescein access to the deeper pore layers, consequently reducing loading capacity.
Precise timing and dosing of potent small-molecule drugs carries significant potential for effective pharmaceutical management of disorders that exhibit time-varying therapeutic windows such as epilepsy. This study demonstrates the use of alumina-coated nanoporous gold (np-Au) thin film electrodes for iontophoretic release of fluorescein as a small-molecule drug surrogate with picogram dosing and a few seconds temporal resolution. A custom microfluidic platform was engineered to trigger molecular release from an integrated np-Au chip and monitor the resulting time-varying fluorescein concentration. Following a systematic study of the influence of applied voltage on loading capacity and release kinetics, a LabVIEW-based closed-loop control interface was employed to demonstrate voltage-gated fluorescein release with pre-programmed arbitrary concentrations waveforms. 26 Alumina-coated nanoporous gold (np-Au) electrodes allow for voltage-gated closed-loop control of small-molecule release. Via leveraging electrical conductivity, microfabrication compatibility, and high effective surface area of np-Au, arbitrary waveforms of release dose are attained, paving the way to the effective management of disorders with time-varying therapeutic windows.
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