In this study we present the fabrication of multilayer microneedles with circular obelisk and beveled-circular obelisk geometries, which have potential applications in implantable drug delivery devices. Micro-milling was adopted as an environmental-friendly and cost-effective way to fabricate primary metal microneedle masters. Polylactic acid (PLA) microneedles with sharp tips were then obtained by micromolding followed by oxygen plasma etching and used for preparing polydimethylsiloxane (PDMS) microneedle molds. A spray deposition process was employed for microneedle fabrication to facilitate the formation of multilayer microneedles while helping in maintenance of drug stability. Multilayer microneedles were successfully formed by sequential spraying of poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) solutions into the mold. The fabricated PLGA-PVP multilayer microneedles penetrated the pig cadaver skin without breakage and released dyes in the skin at different rates, which reveals the potential for implantable microneedles enabling controlled release. Mechanical testing demonstrated that the obelisk-shaped microneedles were mechanically stronger than a pyramid-shaped microneedle and suggested that strong adhesion between PLGA and PVP layers was achieved as well. Structural stability and functionality of a model drug, horseradish peroxidase (HRP), upon spray deposition was examined using circular dichroism (CD) spectroscopy and enzyme activity assay. HRP retained its secondary structure and activity in PVP, whereas HRP in PLGA showed structural changes and reduced activity. Combination of micro-milling and spray deposition would be an attractive way of fabricating drug-containing polymer microneedles with various geometries while reducing prototyping time and process-induced drug instability.

In this study we present polymeric microneedles composed of multiple layers to control drug release kinetics. Layered microneedles were fabricated by spraying poly(lactic-co-glycolic acid) (PLGA) and polyvinylpyrrolidone (PVP) in sequence, and were characterized by mechanical testing and ex vivo skin insertion tests. The compression test demonstrated that no noticeable layer separation occurred, indicating good adhesion between PLGA and PVP layers. Histological examination confirmed that the microneedles were successfully inserted into the skin and indicated biphasic release of dyes incorporated within microneedle matrices. Structural changes of a model protein drug, bovine serum albumin (BSA), in PLGA and PVP matrices were examined by circular dichroism (CD) and fluorescence spectroscopy. The results showed that the tertiary structure of BSA was well maintained in both PLGA and PVP layers while the secondary structures were slightly changed during microneedle fabrication. In vitro release studies showed that over 60% of BSA in the PLGA layer was released within 1 h, followed by continuous slow release over the course of the experiments (7 days), while BSA in the PVP layer was completely released within 0.5 h. The initial burst of BSA from PLGA was further controlled by depositing a blank PLGA layer prior to forming the PLGA layer containing BSA. The blank PLGA layer acted as a diffusion barrier, resulting in a reduced initial burst. The formation of the PLGA diffusion barrier was visualized using confocal microscopy. Our results suggest that the spray-formed multilayer microneedles could be an attractive transdermal drug delivery system that is capable of modulating a drug release profile.

Nanostructured materials such as mesoporous metal oxides and phase-separated block copolymers form the basis for new monolith, membrane, and thin film technologies having applications in energy storage, chemical catalysis, and separations. Mass transport plays an integral role in governing the application-specific performance characteristics of many such materials. The majority of methods employed in their characterization provide only ensemble data, often masking the nanoscale, molecular-level details of materials morphology and mass transport. Single-molecule fluorescence methods offer direct routes to probing these characteristics on a single-molecule/single-nanostructure basis. This article provides a review of single-molecule studies focused on measurements of anisotropic diffusion, adsorption, partitioning, and confinement in nanostructured materials. Experimental methods covered include confocal and wide-field fluorescence microscopy. The results obtained promise to deepen our understanding of mass transport mechanisms in nanostructures, thus aiding in the realization of advanced materials systems.

Developing a facile means of controlling drug release is of utmost interest in drug delivery systems. In this study, core–shell structured nanofibers containing a water-soluble porogen were fabricated via solution blow spinning, to be used as drug-loaded bioactive tissue scaffolds. Hydrophilic polyvinylpyrrolidone (PVP) and hydrophobic poly(ε-caprolactone) (PCL) were chosen to produce the core and the shell compartments of the fiber, respectively. In the core, a hydrophilic sulforhodamine B (SRB) dye was loaded as a model drug. In the PCL shell, two kinds of PVP with different molecular weights (40 kDa and 1300 kDa) were added, and the influence of PVP leaching on the SRB release and cell growth was investigated. The monolithic PCL-shelled fibers displayed a sustained SRB release with a weak burst effect. The addition of PVP in the shell induced a phase separation, forming microscale PVP domains. The PVP domain, acting as a porogen, was leached out in the medium and, as a result, the burst release of SRB was promoted. This burst effect was more prominent with the lower molecular weight PVP. The biocompatibility of the core–shell fibers was evaluated with human epidermal keratinocytes (HEK) by a cell viability assay and microscopic observation of cell proliferation. The HEK cells on fibers with a PVP/PCL composite shell formed self-assembled spherical clusters, displaying higher cell viability and proliferation than those on the monolithic PCL-shelled fibers that induced HEK cell growth in two-dimensional monolayers. The results demonstrate that the presence of hydrophilic porogens on tissue scaffolds can accelerate drug release and enhance cell proliferation by increasing surface wettability, roughness and porosity. The findings of this study provide a basic insight into the construction of bioactive three-dimensional tissue scaffolds.

Polymer microneedles are an attractive way of transdermal delivery of various pharmaceutical compounds. Fabrication of drug-encapsulating polymer microneedles, however, often involves processing conditions unfavorable for maintaining the stability of drugs, including highly concentrated formulations, high temperature and long drying time. The stability of labile substances in biodegradable polymer matrices could also be significantly reduced by the use of organic solvents and emulsification. In this paper, we reported a new fabrication technique called the dual-nozzle spray deposition process, which utilizes a separate deposition of drug and polymer solutions, as a potential way to address the stability issue associated with current microneedle fabrication processes. A model protein, bovine serum albumin (BSA), was successfully incorporated into both water-soluble poly(vinyl alcohol) (PVA) and biodegradable poly(lactic-co-glycolic acid) (PLGA) microneedles by the dual-nozzle spray deposition process. The conformational change of BSA examined by circular dichroism and fluorescence spectroscopy suggests that the developed process helps maintain the structural stability of BSA during encapsulation in both PVA and PLGA matrices. We anticipate that the dual-nozzle spray deposition process would improve the stability of drugs by reducing adverse interaction with solvents and eliminating the emulsification process. Also, the developed process could be an attractive approach to fabricating polymer-based drug delivery devices.