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Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery

1
Nanotechnology Innovation Center of Kansas State, Kansas State University, Manhattan, KS 66506, USA
2
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA
3
QuadMedicine R&D Centre, QuadMedicine Inc., Seongnam 13209, Korea
4
Department of BioNano Technology, College of BioNano Technology, Gachon University, Seongnam 13120, Korea
5
Gachon BioNano Research Institute, Gachon University, Seongnam 13120, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Polymers 2019, 11(2), 369; https://doi.org/10.3390/polym11020369
Received: 14 January 2019 / Revised: 11 February 2019 / Accepted: 16 February 2019 / Published: 20 February 2019
(This article belongs to the Special Issue Materials and Methods for New Technologies in Polymer Processing)
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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. View Full-Text
Keywords: layered microneedles; heterogeneous composition; biphasic release; rapid drug release; sustained drug release; spray deposition layered microneedles; heterogeneous composition; biphasic release; rapid drug release; sustained drug release; spray deposition
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Park, S.C.; Kim, M.J.; Baek, S.-K.; Park, J.-H.; Choi, S.-O. Spray-Formed Layered Polymer Microneedles for Controlled Biphasic Drug Delivery. Polymers 2019, 11, 369.

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