Hielscher Ultrasound Technology

Pharmaceuticals Encapsulated in Lipid Nanoparticles with Ultrasonics

Nano-size drug carriers are widely used to deliver pharmaceutically active compounds into the targeted cells. In order to encapsulate the active substances into a drug carrier with a high bioavailability, solid lipid nanoparticles are used. Ultrasonic nano-emulsification and encapsulation is a reliable technique to produce large quantities of high-quality nano carriers such as solid lipid nanoparticles, nano-structured lipid carriers and liposomes.

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Ultrasonic Nano-Emulsification and Encapsulation

Sonication is capable of disrupting the oil and aqueous phases and mixing tiny oil droplets into water. Since the ultrasonic emulsification process can be precisely controlled, ultrasonic emulsification and the subsequent process of forming solid-lipid nanoparticles is capable to produce loaded nanoparticles sonication can produce significantly lower droplet sizes in comparison to conventional emulsion methods.

Since ultrasonic nano-emulsification and encapsulation can be precisely controlled, the sonication technique allows for an exact control over the solid lipid nanoparticle size and its loading.

Ultrasonic nano-emulsification results in nano-enhanced emulsions, liposomes and solid-lipid nanoparticles for drug delivery.

Ultrasonic nano-emulsification is used to produce loaded nano-emulsions, liposomes and solid-lipid nanoparticles. Sonication produces a narrow droplet distribution and nano-structured particles.

Whilst larger solid lipid nanoparticles (SLNs) can be loaded with a higher concentration of active substances, small-sized SNLs show greatly increased kinetics of absorption and lengthened circulation time in the human organism.

Hielscher Ultrasonics homogenizers give you the full control over the process parameters such as amplitude, temperature, pressure, sonication time and energy input. This enables you to develop a customised recipe for your proprietary solid lipid nanoparticle formulation. The ultrasonic preparation of lipid nanoparticles is compatible with multiple lipid sources and emulsifiers.
Sonication results in a very uniform narrow particle size distribution, therefore leading to a high stability during storage.

Ultrasonic encapsulation is used to produce large volumes of pharmaceutical-grade liposomes with a high load of active substances.

UIP1000hdT with glass flow reactor for solid lipid nanoparticle production

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Ultrasonic encapsulation of pharmaceutical substances in solid lipid nanoparticles (SLNs)

Ultrasonic Preparation of Solid-Lipid Nanoparticles
(Kumar et al. 2019)

The Advantage of Ultrasonic Lipid Nanoparticle Preparation

  • High performance emulsification
  • Exact control over lipid particle size and load
  • High load of active substances
  • Exact control over process parameters
  • Fast Process
  • Non-thermal, precise temp control
  • Linear Scalability
  • Reproducibility
  • Process standardisation / GMP
  • Autoclavable probes and reactors
  • CIP / SIP
Ultrasonic preparation of solid-lipid nanoparticles produces nano-structured drug carriers with a high bioavailability, high stability and low cytotoxicity

Steps of ultrasonic production of Solid-Lipid Nanoparticles
(Kumar et al. 2019)

What are Solid-Lipid Nanoparticles?

Solid lipid nanoparticles (SLNs) are a common form of nano-structured drug carrier, which can encapsulate bioactive or pharmaceutical compounds. They can enhance the delivery of drugs to intestinal lymphatics and to improve the penetration into tissues for a high delivery rate of the therapeutics. SNLs can entrap lipophilic drugs into their lipid core, whilst the surfactant coating makes the nanoparticle water-soluble and gives them thereby a high bioavailability. SNLs have a spherical shape and consist of a solid lipid core stabilized by an emulsifying agent (surfactant, co-surfactants).

Common lipid and triglyceride sources are tricaprin, trilaurin, trimyristin, tripalmitin, tristearin, glyceryl monostearate, glyceryl behenate, glyceryl palmitostearate, cetyl palmitate, stearic acid, palmitic acid, decanoic acid, behenic acid, glycol esters, acylglycerols, waxes etc.

As surfactant in solid lipid nanoparticles often lecithins (e.g. soy lecithin, sunflower lecithin, egg lecithin), phospholipids, phosphatidylcholine, sphingomyelins, bile salts (sodium taurocholate), sterols (cholesterol), poloxamer 188, 182, and 407, poloxamine 908, Tyloxapol, polysorbate 20, 60, and 80, sodium cholate, sodium glycocholate, taurocholic acid sodium salt, taurodeoxycholic acid sodium salt, butanol, butyric acid, dioctyl sodium sulfosuccinate, monooctylphosphoric acid sodium amongst others are used.

Since solid lipid nanoparticles consist in physiologically similar lipids found in the human body, they are considered as well tolerated. They can be administered orally, intravenously and dermally.

High-Performance Ultrasonicators for Solid Lipid Nanoparticles

Precise control over the ultrasonic process parameters by Hielscher Ultrasonics' intelligent softwareHielscher Ultrasonics’ systems are widely used in the pharmaceutical and supplement production to formulate high-quality solid lipid nanoparticles and liposomes loaded with pharmaceutical substances, vitamins, antioxidants, peptides and other bioactive compounds. To meet its customers’ demands, Hielscher supplies ultrasonicators from the compact, yet powerful hand-held lab homogeniser and bench-top ultrasonicators to fully industrial ultrasonic systems for the production of high-volumes of pharmaceutical formulations. A broad range of ultrasonic sonotrodes and reactors are available to ensure an optimal setup for your liposome production. The robustness of Hielscher’s ultrasonic equipment allows for 24/7 operation at heavy duty and in demanding environments.
In order to enable our customers to fulfil Good Manufacturing Practices (GMP) and to establish standardised processes, all digital ultrasonicators are equipped with intelligent software for precise setting of the sonication parameter, continuous process control and automatic recording of all important process parameters on a built-in SD-card. High product quality depends on process control and continuously high processing standards. Hielscher ultrasonicators help you to monitor and standardise your process!
The table below gives you an indication of the approximate processing capacity of our ultrasonicators:

Batch Volume Flow Rate Recommended Devices
1 to 500mL 10 to 200mL/min UP100H
10 to 2000mL 20 to 400mL/min UP200Ht, UP400St
0.1 to 20L 0.2 to 4L/min UIP2000hdT
10 to 100L 2 to 10L/min UIP4000hdT
n.a. 10 to 100L/min UIP16000
n.a. larger cluster of UIP16000

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Hielscher Ultrasonics manufactures high-performance ultrasonic homogenizers for dispersion, emulsification and cell extraction.

High-power ultrasonic homogenizers from lab to pilot and industrial scale.

Literature/References

  • Basarkar A., Devineni D., Palaniappan R., Singh J. (2007): Preparation, characterization, cytotoxicity and transfection efficiency of poly (D, L-lactide- co-glycolide) and poly (D, L-lactic acid) cationic nanoparticles for controlled delivery of plasmid DNA. Int J Pharm 343: 247–254.
  • Zhao K., Li W., Huang T., Luo X., Chen G., Zhang Y., Guo Ch.,
    Dai Ch., Jin Z., Zhao Y., Cui H., Wang Y. (2013): Preparation and Efficacy of Newcastle Disease Virus DNA Vaccine Encapsulated in PLGA Nanoparticles. PLoS ONE 8(12), 2013.


Facts Worth Knowing

Solid Lipid Nanoparticles as Drug Carrier

Solid lipid nanoparticles typically have a spherical shape with an average diameter between 10 and 1000 nanometers. Solid lipid nanoparticles possess a solid lipid core matrix in which lipophilic molecules can be solubilized. The lipid core can consist of different fat compounds, meaning that the term “lipid” is used in wider sense that includes triglycerides (e.g. tristearin), diglycerides (e.g. glycerol bahenate), monoglycerides (e.g. glycerol monostearate), fatty acids (e.g. stearic acid), steroids (e.g. cholesterol), and waxes (e.g. cetyl palmitate). The lipid core is stabilized by (mostly a combination of) emulsifying agents (surfactant) that are chosen depending on the way of administration.

RNA vaccines

RNA vaccines use synthetic messenger RNA (mRNA) strands that encode proteins from the virus surface Those mRNA strands are encapsulated in solid lipid nanoparticles in order to provoke a response of the human immune system to the virus.