Formulation development of antibiotic lipid nanoparticles
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Date
2020-07-17
Authors
Euan Martínez, Arlen Aurora
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Abstract
Lipid nanoparticles (LNPs) are colloidal carriers that can be used for a wide range of therapeutic applications. LNPs have low toxicity, enhanced cellular uptake, and prolonged drug release in comparison with liposomes. Production of LNPs in the laboratory has been reported, but the production methods must be suitable for the clinical translation and the eventual reach to the market.The project focuses on the production of lipid nanoparticles loaded with antibiotics for its incorporation in a bioengineered human skin for wound therapy. The main objective is the GMP production of the nanoparticles following a QbD approach to increase the antibiotic stability and activity and to decrease its toxicity. The nanoparticles are composed of the antibiotic, a combination of lipids, and a surfactant. Surfactants used were sodium dodecyl sulfate, stearic acid, and myristic acid sodium salt. The production of the nanoparticles is performed using the microfluidics system NanoAssemblrTM. Tobramycin was the chosen antibiotic for its effectivity against microorganisms present in burn wounds, since it is water-soluble a hydrophobic ion-pair step with a surfactant is added to modify its solubility. The LNPs are purified using Tangential Flow Filtration and sterilized by filtration to obtain a sterilized suspension.Formulations of nanoparticles using different surfactants were prepared. The characterization was focused on the particle size, morphology, and cytotoxicity. Particle size and polydispersity index were measured using Dynamic Light Scattering. Images of the LNPs were obtained by Cryo-Electron Microscopy. Size evaluation exhibited that formulations are size appropriate (<200 nm) and stable for a period of 30 days. Cryo-EM microscopy checks the particle size and the encapsulation of the antibiotic. Results confirmed that microfluidics is a one-step manufacturing process for nanopharmaceuticals that provide reliable, scalable, and reproducible results.
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Keywords
Lipid nanoparticles, Tobramycin