Anti-solvent precipitation of solid lipid nanoparticles using a microfluidic oscillator mixer

Abstract

cosmetic and pharmaceutical applications. For dermatological applications, they provide many advantages such as enhanced chemical stability, increased skin hydration effect, and prolonged release (e.g., of perfumes, insect repellents). Cosmetic products containing lipid nanoparticles are already available in the market (Müller et al. 2007;Pardeike et al. 2009). SLN are also an attractive option when used as a drug carrier. It may overcome the problems such as insufficient concentration and poor drug solubility. Advantages also include low toxicity, increased drug stability, high drug load, and precise release control. (Mehnert and Mäder 2001;Almeida and Souto 2007;Belliveau et al. 2012).SLN can be produced through high-pressure homogenization. In this method, the lipid is pushed by high pressure through a narrow gap and accelerated to a high velocity. Large shear stress and cavitation forces will be produced that break the lipid into nanoparticles. This process is energy intensive as the required pressure is up to several hundred bars or even higher. SLN are also prepared by precipitation. The lipid is first dissolved in a solvent. Then, upon either evaporation of the solvent or addition of an anti-solvent, a nanoparticle dispersion will be formed by precipitation of the lipid (Sjöström and Bergenståhl 1992;Dong et al. 2012). Other methods include microemulsion, higher shear homogenization, and ultrasound. More detailed discussion can be found in Mehnert and Mäder (2001).The property of SLN is largely influenced by the size, uniformity, and morphology. Usually, smaller and more uniform SLN are preferred for higher stability, better absorption, and precise release control. In the precipitation synthesis method, one important factor that influences the quality of SLN is the mixing process. The mixing time need to be less than the precipitation time. Otherwise, slow and incomplete mixing will lead to large and wide Abstract The mixing process is critical in the anti-solvent precipitation process of micro-/nanoparticles. It may directly determine the quality of particles, especially the size and uniformity. In this study, a previously developed microfluidic oscillator mixer is used for anti-solvent precipitation of solid lipid (Gelucire 44/14) nanoparticles. This micromixer generates high-frequency oscillatory flow to enhance the fluid mixing. Based on the design, high flow rates of up to 50 ml/min can be achieved to allow relatively high throughput production. Results show that, within a wide concentration range from 10 to 300 mg/ml, solid lipid particles of 50-240 nm can be produced with the polydispersity index ranging from around 0.16 to 0.26. The influences of the anti-solvent to solution flow rate ratio, the geometrical and operating parameters of the oscillator mixer including the secondary chamber depth, and pumping pressure are investigated. For comparison, the same process was also conducted using a static chaotic mixer. Relevant findings provide useful reference for the performance and potential applicatio...

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Microfluidic Synthesis and Biological Evaluation of Photothermal Biodegradable Copper Sulfide Nanoparticles

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Microfluidic based high throughput synthesis of lipid-polymer hybrid nanoparticles with tunable diameters

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