Generic placeholder image

Pharmaceutical Nanotechnology


ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Preparation of Nanostructured Lipid Drug Delivery Particles Using Microfluidic Mixing

Author(s): Linda Hong, Yao-Da Dong and Ben J. Boyd*

Volume 7, Issue 6, 2019

Page: [484 - 495] Pages: 12

DOI: 10.2174/2211738507666191004123545


Background: Cubosomes are highly ordered self-assembled lipid particles analogous to liposomes, but with internal liquid crystalline structure. They are receiving interest as stimuli responsive delivery particles, but their preparation typically requires high energy approaches such as sonication which is not favourable in many applications.

Objective: Here we investigated the impact of microfluidic preparation on particle size distribution and internal structure of cubosomes prepared from two different lipid systems, phytantriol and glyceryl monooleate (GMO).

Methods: The impact of relative flow rates of the aqueous and organic streams, the total flow rate and temperature were investigated in a commercial microfluidic system. The particle size distribution and structure were measured using dynamic light scattering and small angle X-ray scattering respectively.

Results: Phytantriol based particles were robust to different processing conditions, while cubosomes formed using GMO were more sensitive to composition both locally and globally, which reflects their preparation using other techniques.

Conclusion: Thus, in summary microfluidics represents a reproducible and versatile method to prepare complex lipid particle dispersions such as cubosomes.

Keywords: Cubosome, glyceryl monooleate, lipid drug delivery, microfluidics, phytantriol, small angle X-ray scattering, solvent dilution.

Graphical Abstract
Fong WK, Negrini R, Vallooran JJ, Mezzenga R, Boyd BJ. Responsive self-assembled nanostructured lipid systems for drug delivery and diagnostics. J Colloid Interface Sci 2016; 484: 320-39.
[] [PMID: 27623190]
Lyon PC, Griffiths LF, Lee J, et al. Clinical trial protocol for TARDOX: a phase I study to investigate the feasibility of targeted release of lyso-thermosensitive liposomal doxorubicin (ThermoDox®) using focused ultrasound in patients with liver tumours. J Ther Ultrasound 2017; 5: 28.
[] [PMID: 29118984]
Lancelot A, Sierra T, Serrano JL. Nanostructured liquid-crystalline particles for drug delivery. Expert Opin Drug Deliv 2014; 11(4): 547-64.
[] [PMID: 24490701]
Mo J, Milleret G, Nagaraj M. Liquid crystal nanoparticles for commercial drug delivery. Liq Cryst Rev 2017; 5(2): 69-85.
Du JD, Hong L, Tan A, Boyd BJ. Naphthalocyanine as a new photothermal actuator for lipid-based drug delivery systems. J Phys Chem B 2018; 122(5): 1766-70.
[] [PMID: 29316389]
Paasonen L, Sipila T, Subrizi A, et al. Gold-embedded photosensitive liposomes for drug delivery: triggering mechanism and intracellular release. J Control Rel Soc 2010; 147(1): 136-43.
Aleandri S, Speziale C, Mezzenga R, Landau EM. Design of light-triggered lyotropic liquid crystal mesophases and their application as molecular switches in “On Demand” release. Langmuir 2015; 31(25): 6981-7.
[] [PMID: 26039728]
Mendozza M, Montis C, Caselli L, Wolf M, Baglioni P, Berti D. On the thermotropic and magnetotropic phase behavior of lipid liquid crystals containing magnetic nanoparticles. Nanoscale 2018; 10(7): 3480-8.
[] [PMID: 29404545]
Negrini R, Fong WK, Boyd BJ, Mezzenga R. pH-responsive lyotropic liquid crystals and their potential therapeutic role in cancer treatment. Chem Commun 2015; 51(30): 6671-4.
[] [PMID: 25783035]
Negrini R, Mezzenga R. pH-responsive lyotropic liquid crystals for controlled drug delivery. Langmuir 2011; 27(9): 5296-303.
[] [PMID: 21452814]
Chong JYT, Mulet X, Waddington LJ, Boyd BJ, Drummond CJ. Steric stabilisation of self-assembled cubic lyotropic liquid crystalline nanoparticles: high throughput evaluation of triblock polyethylene oxide-polypropylene oxide-polyethylene oxide copolymers. Soft Matter 2011; 7(10): 4768.
Zhai J, Waddington L, Wooster TJ, Aguilar MI, Boyd BJ. Revisiting β-casein as a stabilizer for lipid liquid crystalline nanostructured particles. Langmuir 2011; 27(24): 14757-66.
[] [PMID: 22026367]
Grace JL, Alcaraz N, Truong NP, et al. Lipidated polymers for the stabilization of cubosomes: nanostructured drug delivery vehicles. Chem Commun (Camb) 2017; 53(76): 10552-5.
[] [PMID: 28890981]
Zhai J, Suryadinata R, Luan B, et al. Amphiphilic brush polymers produced using the RAFT polymerisation method stabilise and reduce the cell cytotoxicity of lipid lyotropic liquid crystalline nanoparticles. Faraday Discuss 2016; 191: 545-63.
[] [PMID: 27453499]
Fong WK, Salentinig S, Prestidge CA, Mezzenga R, Hawley A, Boyd BJ. Generation of geometrically ordered lipid-based liquid-crystalline nanoparticles using biologically relevant enzymatic processing. Langmuir 2014; 30(19): 5373-7.
[] [PMID: 24783947]
Hong L, Salentinig S, Hawley A, Boyd BJ. Understanding the mechanism of enzyme-induced formation of lyotropic liquid crystalline nanoparticles. Langmuir 2015; 31(24): 6933-41.
[] [PMID: 26029994]
Spicer PT, Hayden KL, Lynch ML, Ofori-Boateng A, Burns JL. Novel process for producing cubic liquid crystalline nanoparticles (cubosomes). Langmuir 2001; 17(19): 5748-56.
Kastner E, Kaur R, Lowry D, Moghaddam B, Wilkinson A, Perrie Y. High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. Int J Pharm 2014; 477(1-2): 361-8.
[] [PMID: 25455778]
Belliveau NM, Huft J, Lin PJ, et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 2012; 1 e37
[] [PMID: 23344179]
Stroock AD, Dertinger SKW, Ajdari A, Mezic I, Stone HA, Whitesides GM. Chaotic mixer for microchannels. Science 2002; 295(5555): 647-51.
[] [PMID: 11809963]
Akhlaghi SP, Ribeiro IR, Boyd BJ, Loh W. Impact of preparation method and variables on the internal structure, morphology, and presence of liposomes in phytantriol-pluronic(®) F127 cubosomes. Colloids Surf B Biointerfaces 2016; 145: 845-53.
[] [PMID: 27315333]
Kirby NM, Mudie ST, Hawley AM, et al. A low-background-intensity focusing small-angle X-ray scattering undulator beamline. J Appl Cryst 2013; 46(6): 1670-80.
Hyde ST. Identification of lyotropic liquid crystalline mesophases. In: Holmberg K, Ed. Handbook of applied surface and colloid chemistry. Wiley: United States 2001; pp. 299-332.
Dong YD, Larson I, Hanley T, Boyd BJ. Bulk and dispersed aqueous phase behavior of phytantriol: effect of vitamin E acetate and F127 polymer on liquid crystal nanostructure. Langmuir 2006; 22(23): 9512-8.
[] [PMID: 17073473]
Nakano M, Teshigawara T, Sugita A, et al. Dispersions of liquid crystalline phases of the monoolein/oleic acid/pluronic F127 system. Langmuir 2002; 18(24): 9283-8.
Khan IU, Serra CA, Anton N, Vandamme T. Microfluidics: a focus on improved cancer targeted drug delivery systems. J Control Release 2013; 172(3): 1065-74.
Guimarães Sá Correia M, Briuglia ML, Niosi F, Lamprou DA. Microfluidic manufacturing of phospholipid nanoparticles: Stability, encapsulation efficacy, and drug release. Int J Pharm 2017; 516(1-2): 91-9.
[] [PMID: 27840162]
Kim H, Sung J, Chang Y, Alfeche A, Leal C. Microfluidics synthesis of gene silencing cubosomes. ACS Nano 2018; 12(9): 9196-205.
[] [PMID: 30081623]
Volpatti LR, Yetisen AK. Commercialization of microfluidic devices. Trends Biotechnol 2014; 32(7): 347-50.
[] [PMID: 24954000]
Zhigaltsev IV, Belliveau N, Hafez I, et al. Bottom-up design and synthesis of limit size lipid nanoparticle systems with aqueous and triglyceride cores using millisecond microfluidic mixing. Langmuir 2012; 28(7): 3633-40.
[] [PMID: 22268499]
Kastner E, Verma V, Lowry D, Perrie Y. Microfluidic-controlled manufacture of liposomes for the solubilisation of a poorly water soluble drug. Int J Pharm 2015; 485(1-2): 122-30.
[] [PMID: 25725309]
Jahn A, Vreeland WN, Gaitan M, Locascio LE. Controlled vesicle self-assembly in microfluidic channels with hydrodynamic focusing. J Am Chem Soc 2004; 126(9): 2674-5.
[] [PMID: 14995164]

© 2022 Bentham Science Publishers | Privacy Policy