Antisolvent precipitation of lipid nanoparticles in microfluidic systems – A comparative study

Riewe, Juliane; Erfle, Peer; Melzig, Sebastian; Kwade, Arno; Dietzel, Andreas; Bunjes, Heike

doi:10.1016/j.ijpharm.2020.119167

Cited by 26 publications

(33 citation statements)

References 44 publications

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“…[63] To narrow down nanoparticle size distribution, a homogeneous and supersaturated solution of lipids is favored for spontaneous nucleation. [68] Mixing time plays a critical role in controlling nanoprecipitation. [69] To get a smaller nanoparticle size, mixing time should be less than the characteristic time of precipitation, which means that mixing completes before precipitation occurs.…”

Section: Bulk Nanoprecipitationmentioning

confidence: 99%

Lipid Nanoparticles for Drug Delivery

Wang

Liu

et al. 2021

Advanced NanoBiomed Research

186

110

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Lipid nanoparticles have attracted significant interests in the last two decades, and have achieved tremendous clinical success since the first clinical approval of Doxil in 1995. At the same time, lipid nanoparticles have also demonstrated enormous potential in delivering nucleic acid drugs as evidenced by the approval of two RNA therapies and mRNA COVID‐19 vaccines. In this review, an overview on different classes of lipid nanoparticles, including liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, is first provided, followed by the introduction of their preparation methods. Then the characterizations of lipid nanoparticles are briefly reviewed and their applications in encapsulating and delivering hydrophobic drugs, hydrophilic drugs, and RNAs are highlighted. Finally, various applications of lipid nanoparticles for overcoming different delivery challenges, including crossing the blood–brain barrier, targeted delivery, and various routes of administration, are summarized. Lipid nanoparticles as drug delivery systems offer many attractive benefits such as great biocompatibility, ease of preparation, feasibility of scale‐up, nontoxicity, and targeted delivery, while current challenges in drug delivery warrant future studies about structure–function correlations, large‐scale production, and targeted delivery to realize the full potential of lipid nanoparticles for wider clinical and pharmaceutical applications in future.

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Section: Bulk Nanoprecipitationmentioning

confidence: 99%

Lipid Nanoparticles for Drug Delivery

Wang

Liu

et al. 2021

Advanced NanoBiomed Research

186

110

View full text Add to dashboard Cite

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“…However, it was previously stated that even in segmented flow micromixers, the fouling effect might occur depending on the type of lipid used (Riewe et al., 2020 ) besides the surface properties of the inner channels (Erfle et al., 2019 ); shedding light on the proper selection of components and experimental setup, as well. The solubility of the lipid is of great importance; Softisan ® 100 (a blend of solid triglycerides) ethanolic solution resulted in fouling in a segmented flow micromixer due to its low solubility in ethanol, resulting in its crystallization (Erfle et al., 2017 ).…”

Section: Approaches For Efficient Microfluidicsmentioning

confidence: 99%

Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects

et al. 2022

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Microfluidics is used to manipulate fluid flow in micro-channels to fabricate drug delivery vesicles in a uniform tunable size. Thanks to their designs, microfluidic technology provides an alternative and versatile platform over traditional formulation methods of nanoparticles. Understanding the factors that affect the formulation of nanoparticles can guide the proper selection of microfluidic design and the operating parameters aiming at producing nanoparticles with reproducible properties. This review introduces the microfluidic systems’ continuous flow (single-phase) and segmented flow (multiphase) and their different mixing parameters and mechanisms. Furthermore, microfluidic approaches for efficient production of nanoparticles as surface modification, anti-fouling, and post-microfluidic treatment are summarized. The review sheds light on the used microfluidic systems and operation parameters applied to prepare and fine-tune nanoparticles like lipid, poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles as well as cross-linked nanoparticles. The approaches for scale-up production using microfluidics for clinical or industrial use are also highlighted. Furthermore, the use of microfluidics in preparing novel micro/nanofluidic drug delivery systems is presented. In conclusion, the characteristic vital features of microfluidics offer the ability to develop precise and efficient drug delivery nanoparticles.

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“…A continuous anti-solvent precipitation procedure with a T-junction was selected to prepare the SC-PEG NPs. This procedure has been used to prepare NPs [ 18 , 19 ] and is superior to the conventional bulk preparation method, such as the solvent evaporation method, in terms of scalability and reproducibility [ 20 , 21 ]. It was also reported that process parameters, such as temperature, flow rate, and flow rate ratio, affect the characteristics of NPs [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Processing Parameters and Ion Excipients Affect the Physicochemical Characteristics of the Stereocomplex-Formed Polylactide-b-Polyethylene Glycol Nanoparticles and Their Pharmacokinetics

et al. 2022

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To optimize the characteristics of stereocomplex polylactide-b-polyethylene glycol nanoparticles (SC-PEG NPs) in terms of pharmacokinetics (PK), we chose continuous anti-solvent precipitation with a T-junction as a preparation method and investigated the effect of using solvents containing an ion excipient (lithium bromide, LiBr) on the characteristics of SC-PEG NPs by changing the processing temperature and total flow rate (TFR). Processing temperatures above the melting temperature (Tm) of the PEG domain produced a sharper polydispersity and denser surface PEG densities of SC-PEG NPs than those produced by processing temperatures below the Tm of the PEG domains. Response surface analysis revealed that a higher LiBr concentration and slower TFR resulted in larger and denser hydrodynamic diameters (Dh) and surface PEG densities, respectively. However, a high concentration (300 mM) of LiBr resulted in a decreased drug loading content (DLC). 14C-tamoxifen-loaded 111In-SC-PEG NPs with larger Dh and denser surface PEG densities showed a prolonged plasma retention and low tissue distribution after intravenous injection in mice. These results indicate that the novel strategy of using solvents containing LiBr at different processing temperatures and TFR can broadly control characteristics of SC-PEG NPs, such as Dh, surface PEG densities, and DLC, which alter the PK profiles and tissue distributions.

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Antisolvent precipitation of lipid nanoparticles in microfluidic systems – A comparative study

Cited by 26 publications

References 44 publications

Lipid Nanoparticles for Drug Delivery

Lipid Nanoparticles for Drug Delivery

Merits and advances of microfluidics in the pharmaceutical field: design technologies and future prospects

Processing Parameters and Ion Excipients Affect the Physicochemical Characteristics of the Stereocomplex-Formed Polylactide-b-Polyethylene Glycol Nanoparticles and Their Pharmacokinetics

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