Microfluidic preparation of drug-loaded PEGylated liposomes, and the impact of liposome size on tumour retention and penetration

Dong, Yao; Tchung, Estefania; Nowell, Cameron J.; Kağa, Sadık; Leong, Nathania; Mehta, Dharmini; Kaminskas, Lisa M.; Boyd, Ben J.

doi:10.1080/08982104.2017.1391285

Cited by 45 publications

(32 citation statements)

References 25 publications

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“…Successful formulation of safe, stable and efficient nanocarriers, therefore, requires the preparation of homogenous (monodisperse) populations of nanocarriers of a certain size. However, it is difficult to control the particle size distribution without considering the composition of the nanocarriers and the nature of the solvents and co-solvents used during their preparation [ 8 , 75 , 76 ]. Following preparation, nanocarriers must be characterized to assure their suitability for in vitro and in vivo applications.…”

Section: Polydispersity Indexmentioning

confidence: 99%

Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems

et al. 2018

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Lipid-based drug delivery systems, or lipidic carriers, are being extensively employed to enhance the bioavailability of poorly-soluble drugs. They have the ability to incorporate both lipophilic and hydrophilic molecules and protecting them against degradation in vitro and in vivo. There is a number of physical attributes of lipid-based nanocarriers that determine their safety, stability, efficacy, as well as their in vitro and in vivo behaviour. These include average particle size/diameter and the polydispersity index (PDI), which is an indication of their quality with respect to the size distribution. The suitability of nanocarrier formulations for a particular route of drug administration depends on their average diameter, PDI and size stability, among other parameters. Controlling and validating these parameters are of key importance for the effective clinical applications of nanocarrier formulations. This review highlights the significance of size and PDI in the successful design, formulation and development of nanosystems for pharmaceutical, nutraceutical and other applications. Liposomes, nanoliposomes, vesicular phospholipid gels, solid lipid nanoparticles, transfersomes and tocosomes are presented as frequently-used lipidic drug carriers. The advantages and limitations of a range of available analytical techniques used to characterize lipidic nanocarrier formulations are also covered.

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Section: Polydispersity Indexmentioning

confidence: 99%

Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems

et al. 2018

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“…This can be achieved in a single process without the need for postprocessing or changing the lipid composition of the liposomes 30,35 . Cancer therapy is one example where size reduction of liposomes is desirable 34 . A recent study by Dong et al demonstrated that by using MF methodology it was possible to reduce the size of doxorubicin-loaded liposomes to 50 nm.…”

Section: Fabrication and Physicochemical Characterization Of L-aunp Hmentioning

confidence: 99%

“…Furthermore, this control is achieved in a single step without the need for additional post-production processing through extrusion or sonication. Very promising examples of liposomal systems with high payload capacity of hydrophilic and/or lipophilic drugs have been reported 34,35,36,37,38 . Moreover, advances in the design of integrated microfluidic devices allow the combination of in-line liposome fabrication with other processes such as remote drug loading 39 , and complexation with genetic material such as pDNA and siRNA 40 .…”

Section: Introductionmentioning

confidence: 99%

Enhanced Intraliposomal Metallic Nanoparticle Payload Capacity Using Microfluidic-Assisted Self-Assembly

et al. 2019

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Hybrids composed of liposomes (L) and metallic nanoparticles (NP) hold great potential for imaging and drug delivery purposes. However, the efficient incorporation of metallic nanoparticles into liposomes using conventional methodologies has so far proved to be challenging. In this study, we report the fabrication of hybrids of liposomes and hydrophobic gold nanoparticles of size 2-4 nm (Au) using a microfluidic assisted self-assembly process. The incorporation of increasing amounts of Au nanoparticles into liposomes was examined using microfluidics and compared to L-AuNP hybrids prepared by the reverse-phase evaporation method. Our microfluidics strategy produced L-AuNP hybrids with a homogeneous size distribution, smaller polydispersity index, and a 3-fold increase in loading efficiency when compared to those hybrids prepared using the reverse-phase method of production. Quantification of the loading efficiency was determined by ultraviolet spectroscopy, inductively coupled plasma mass spectroscopy and centrifugal field flow fractionation and confirmed qualitatively by transmission electron microscopy. The higher loading of gold nanoparticles into the liposomes achieved using microfluidics produced a slightly thicker and more rigid bilayer as determined with small angle neutron scattering. These observations were confirmed using fluorescent anisotropy and atomic force microscopy, respectively. Structural characterization of the liposomal-nanoparticle hybrids with cryo-electron microscopy revealed the coexistence of membrane-embedded and interdigitated nanoparticle-rich domains suggesting AuNP incorporation through hydrophobic interactions. The microfluidic technique that we describe in this study allows for the automated production of monodisperse liposomal-nanoparticle hybrids with high loading capacity highlighting the utility of microfluidics to improve the payload of metallic nanoparticles within liposomes, thereby enhancing their application for imaging and drug delivery.

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“…PEG-coated particles are known as long circulating lipid particles and have longer half-lives compared to conventional or targeted LNPs. 42 Blood samples collected 24 hours post-administration also confirmed the total clearance of non-targeted PEG-LNP(Cal), PEG-LNP(Cal)-IgG, and PEG-LNP(Cal)-αmCD163 in blood, comparable to the control PBS mice group (not shown). At 25 hours post-LNP administration, ex vivo imaging of the organs confirmed the accumulation of PEG-LNP(Cal) only in the liver, in contrast to the accumulation of PEG-LNP(Cal)-αmCD163 in the liver and spleen.…”

Section: Effects Of Encapsulated Calcitriol On Proinflammatory Cytokimentioning

confidence: 57%

<p>Targeted lipid nanoparticle delivery of calcitriol to human monocyte-derived macrophages in vitro and in vivo: investigation of the anti-inflammatory effects of calcitriol</p>

Rafique¹,

Etzerodt²,

Graversen³

et al. 2019

IJN

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Background: Vitamin D 3 possesses anti-inflammatory and modulatory properties in addition to its role in calcium and phosphate homeostasis. Upon activation, macrophages (M) can initiate and sustain pro-inflammatory cytokine production in inflammatory disorders and play a pathogenic role in certain cancers. Purpose: The main purpose of this study was to encapsulate and specifically target calcitriol to macrophages and investigate the anti-inflammatory properties of calcitriol in vitro and in vivo. Methods: In this study we have designed and developed near-infrared calcitriol PEGylated nanoparticles (PEG-LNP(Cal)) using a microfluidic mixing technique and modified lipid nanoparticles (LNPs) to target the M specific endocytic receptor CD163. We have investigated LNP cellular uptake and anti-inflammatory effect in LPS-induced M in vitro by flow cytometry, confocal microscopy and gene expression analyses. LNP pharmacodynamics, bio-distribution and organ specific LNP accumulation was also investigated in mice in vivo. Results: In vitro, we observed the specific uptake of PEG-LNP(Cal)-hCD163 in human M, which was significantly higher than the non-specific uptake of control PEG-LNP(Cal)-IgG(h) in M. Pretreatment with encapsulated calcitriol was able to attenuate intracellular TNF-expression, and M surface marker HLA-DR expression more efficiently than free calcitriol in LPS-induced M in vitro. Encapsulated calcitriol diminished mRNA gene levels of TNF-, NF-B, MCP-1 and IL-6, while upregulating IL-10. TNF-and IL-6 protein secretion also decreased. In mice, an in vivo pharmacodynamic study of PEG-LNP(Cal) showed a rapid clearance of IgG and CD163 modified LNPs compared to PEG-LNP(Cal). Antibody modified PEG-LNP(Cal) accumulated in the liver, spleen and kidney, whereas unmodified PEG-LNP(Cal) accumulation was only observed in the liver. Conclusion: Our results show that calcitriol can be effectively targeted to M. Our data confirms the anti-inflammatory properties of calcitriol and this may be a potential way to deliver high dose bioactive calcitriol to M during inflammation in vivo.

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Microfluidic preparation of drug-loaded PEGylated liposomes, and the impact of liposome size on tumour retention and penetration

Cited by 45 publications

References 25 publications

Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems

Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems

Enhanced Intraliposomal Metallic Nanoparticle Payload Capacity Using Microfluidic-Assisted Self-Assembly

<p>Targeted lipid nanoparticle delivery of calcitriol to human monocyte-derived macrophages in vitro and in vivo: investigation of the anti-inflammatory effects of calcitriol</p>

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