title: Nanostructured lipid carrier-loaded hyaluronic acid microneedles for controlled dermal delivery of a lipophilic molecule.
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.
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Sang Gon
authors.initials: SG
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Jae Han
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Kyu Ho
authors.initials: KH
authors.lastname: Jeong
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, South Korea.
authors.forename: Huisuk
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, South Korea.
authors.forename: Miroo
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul, South Korea.
authors.forename: Hyungil
authors.initials: H
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Keimyung University, Daegu, South Korea.
authors.forename: Sangkil
authors.initials: S
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung-Ang University, Seoul, South Korea.
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006820:Hyaluronic Acid / Q000737:chemistry; D007271:Injections, Intradermal / Q000295:instrumentation; D008422:Materials Testing; D008845:Microinjections / Q000295:instrumentation*; D050997:Nanomedicine / Q000295:instrumentation; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009339:Needles; D010078:Oxazines / Q000008:administration & dosage / Q000737:chemistry*; D012867:Skin / Q000737:chemistry*; D013552:Swine; D013556:Swine, Miniature; D014018:Tissue Distribution
chemical_list: D003692:Delayed-Action Preparations; D010078:Oxazines; D006820:Hyaluronic Acid; C044808:nile red
keywords: controlled release; dermal delivery; hyaluronic acid; nanostructured lipid carriers; polymeric microneedles