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Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule

Authors Lee SG, Jeong JH, Lee KM, Jeong KH, Yang H, Kim M, Jung H, Lee S, Choi YW

Received 14 September 2013

Accepted for publication 23 October 2013

Published 31 December 2013 Volume 2014:9(1) Pages 289—299

DOI https://doi.org/10.2147/IJN.S54529

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Sang Gon Lee,1,* Jae Han Jeong,1,* Kyung Min Lee,1 Kyu Ho Jeong,1 Huisuk Yang,2 Miroo Kim,2 Hyungil Jung,2 Sangkil Lee,3 Young Wook Choi1

1College of Pharmacy, Chung-Ang University, Seoul, South Korea; 2Department of Biotechnology, Yonsei University, Seoul, South Korea; 3College of Pharmacy, Keimyung University, Daegu, South Korea

*These authors contributed equally to this work

Abstract: Nanostructured lipid carriers (NLCs) were employed to formulate a lipophilic drug into hydrophilic polymeric microneedles (MNs). Hyaluronic acid (HA) was selected as a hydrophilic and bioerodible polymer to fabricate MNs, and nile red (NR) was used as a model lipophilic molecule. NR-loaded NLCs were consolidated into the HA-based MNs to prepare NLC-loaded MNs (NLC-MNs). A dispersion of NLCs was prepared by high-pressure homogenization after dissolving NR in Labrafil and mixing with melted Compritol, resulting in 268 nm NLCs with a polydispersity index of 0.273. The NLC dispersion showed a controlled release of NR over 24 hours, following Hixson–Crowell's cube root law. After mixing the NLC dispersion with the HA solution, the drawing lithography method was used to fabricate NLC-MNs. The length, base diameter, and tip diameter of the NLC-MNs were approximately 350, 380, and 30 µm, respectively. Fluorescence microscopic imaging of the NLC-MNs helped confirm that the NR-loaded NLCs were distributed evenly throughout the MNs. In a skin permeation study performed using a Franz diffusion cell with minipig dorsal skin, approximately 70% of NR was localized in the skin after 24-hour application of NLC-MNs. Confocal laser scanning microscopy (z-series) of the skin at different depths showed strong fluorescence intensity in the epidermal layer, which appeared to spread out radially with the passage of time. This study indicated that incorporation of drug-loaded NLCs into MNs could represent a promising strategy for controlled dermal delivery of lipophilic drugs.

Keywords: polymeric microneedles, nanostructured lipid carriers, dermal delivery, controlled release, hyaluronic acid

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