Liquid crystal nanoparticle formulation as an oral drug delivery system for liver-specific distribution

Abstract

Liquid crystal nanoparticles have been utilized as an efficient tool for drug delivery with enhanced bioavailability, drug stability, and targeted drug delivery. However, the high energy requirements and the high cost of the liquid crystal preparation have been obstacles to their widespread use in the pharmaceutical industry. In this study, we prepared liquid crystal nanoparticles using a phase-inversion temperature method, which is a uniquely low energy process. Particles prepared with the above method were estimated to be ~100 nm in size and exhibited a lamellar liquid crystal structure with orthorhombic lateral packing. Pharmacokinetic and tissue distribution studies of a hydrophobic peptide-based drug candidate formulated with the liquid crystal nanoparticles showed a five-fold enhancement of bioavailability, sustained release, and liver-specific drug delivery compared to a host–guest complex formulation.

Keywords:

• LCNP
• PIT
• sustained release
• bioavailability

Supplementary materials

Table S1 Body weights and dose volumes of Sprague Dawley rats for the pharmacokinetic study

Table S2 Body weights and dose volumes of Sprague Dawley rats for the tissue distribution study

Table S3 Compositions of LCNPs for the pharmacokinetic study

Figure S1 High-performance liquid chromatography analysis of BMK-20113 incorporated into the liquid crystal nanoparticles (LCNPs).

Notes: (A) BMK-20113 in tetrahydrofuran, (B) LCNP-#8 and (C) LCNP-#11.

Abbreviations: min, minute(s); Sig, signal; Ref, reference.

Figure S2 The differential scanning calorimetry results.

Notes: Emulgade SE-PF (A), tetradecyl tetradecanoate (B) and PEG-12 cetostearyl ether (C).

Abbreviations: PEG-12, polyethylene glycol; Exo up, exothermic heat flow.

Figure S3 Transmission electron microscopy image of BMK-20113 recrystallization of LCNP-#12.

Abbreviation: LCNP, liquid crystal nanoparticle.

Figure S4 Transmission electron microscopy image of LCNP-#8 and #11 in an acidic condition (pH 1.5).

Abbreviation: LCNP, liquid crystal nanoparticle.

General information

High-performance liquid chromatography analyses were performed with an HP1100 system (Agilent Technologies, Santa Clara, CA, USA), comprised of HP Chemstation software, an auto sampler, a quaternary pump, and a photodiode array detector. C18 Vydac 218TP54 column 250×4.6 mm in diameter (5 µm particle size) was employed for the analysis. The mobile phase for the analysis was 0.1% trifluoroacetic acid in water (A) and acetonitrile (B) at a flow rate of 1 mL/min at 20°C. Method: 100% A and 0% B (0 minutes), 100% B (10 minutes), 100% B (20 minutes), 0% B (22 minutes), 0% B (25 minutes).

Acknowledgments

This research was supported by the Korean Ministry of Education, Science and Technology (grant number 2012M3A7B4049644, Nano Material Development Program through the National Research Foundation of Korea, NRF).

Disclosure

The authors report no conflicts of interest in this work.