Abstract
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.
Highlights
Microneedles are designed to deliver pharmaceutical compounds across the skin in a minimally invasive manner and could offer a number of advantages over traditional needle injections, including reduced injection pain and improved patient compliance [1,2,3]
Coumarin 314 and sulforhodamine B (SRB) fluorescent dyes were added to poly(lactic-co-glycolic acid) (PLGA) and PVP solutions, respectively, to distinguish each layer
The results demonstrate that drug loading amounts can be controlled by adjusting spraying parameters and can be estimated at a given initial drug concentration
Summary
Microneedles are designed to deliver pharmaceutical compounds across the skin in a minimally invasive manner and could offer a number of advantages over traditional needle injections, including reduced injection pain and improved patient compliance [1,2,3]. Since microneedles can target the antigen-presenting immune cells of the skin, application of microneedles in vaccination and immunotherapy has received great attention in recent years [4,5]. When composed of biocompatible polymers, microneedles can be manufactured at low costs and be safely disposed of after use [6,7]. Polymers, microneedles can be manufactured at low costs and be safely disposed of after use [6,7]. Rapid drug release can utilizing the dissolution and degradation properties of materials. In some cases, sustained release of drugs desirable to improve the treatment efficiency and patient compliance and to reduce undesirable side is desirable to improve the treatment efficiency and patient compliance and to reduce undesirable effects by providing optimal drug concentrations over a prolonged period [14,15]. For some drugs or vaccines, biphasic release would be more desirable form microneedles [16,17,18,19,20]. efficiency
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