Magnetoliposomes for dual cancer therapy

Rodrigues, Ana Rita Oliveira; Almeida, Bernardo; Araújo, João P.; Queiroz, Maria João R. P.; Coutinho, Paulo J. G.; Castanheira, Elisabete M. S.

doi:10.1016/b978-0-12-813661-4.00011-0

“…where is the particles mass, v the velocity and is the sum of all forces acting on the particles. For the magnetic separation system, the particles' forces were the drag force (4) and the magnetic force, which is dependent on the magnetic flux density distribution imposed by the applied magnetic field physic (5). In the case of the AsPFF separation system, the involved forces were the drag force defined in (4) and the lift force in the pinched segment (7).…”

Section: Particle Tracing Modelmentioning

confidence: 99%

“…As a result, MLs have enabled various potential therapeutic strategies for conditions ranging from Parkinson's disease to cancer [2,3]. This ample range of applications could be attributed to the suitability of the contained MNPs as contrast agents, drug delivery vehicles, and enablers of localized hyperthermia upon magnetic stimulation [1,4,5]. Over the past few years, several techniques have been proposed for the preparation of MLs, in which MNPs can be encapsulated in the aqueous lumen, embedded in the lipid bilayer, or conjugated on the surface of the liposomes [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

“…This ample range of applications could be attributed to the suitability of the contained MNPs as contrast agents, drug delivery vehicles, and enablers of localized hyperthermia upon magnetic stimulation [1,4,5]. Over the past few years, several techniques have been proposed for the preparation of MLs, in which MNPs can be encapsulated in the aqueous lumen, embedded in the lipid bilayer, or conjugated on the surface of the liposomes [5][6][7][8]. Despite the progress, these methods pose some challenges, including the relatively large particle size distribution, heterogeneous morphology, and, most importantly, the difficulty in separating the non-encapsulated/unbound MNPs [9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

In Silico Analysis of Microfluidic Systems for the Purification of Magnetoliposomes

Torres

¹

,

Aranguren

²

,

Reyes

³

et al. 2020

The 2nd International Online-Conference on Nanomaterials

0

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Magnetite nanoparticles (MNPs) have been considered for several applications in drug delivery. However, the main challenge is to assure high cell-penetration levels, especially when dealing with cargoes that show limited membrane passing. A strategy is to encapsulate the MNPs into liposomes to form magnetoliposomes (MLs) capable of fusing with membranes to achieve high delivery rates. MLs have therefore been used as carriers in the biomedical field due to their ability to release active molecules that can be used in treatments of diverse diseases. There are several techniques to produce such encapsulates, however, the main challenge is that the process often leads to an important fraction of non-encapsulated MNPs. Purification of such a fraction is challenging because of the small size difference between the particles and the MLs and the reduced magnetic responsiveness. Seeking to obtain pure MLs with potential use in the medical field, the following study presents finite element simulations using COMSOL Multiphysics of two purification methods. Accordingly, we implemented the magnetic and asymmetric pinched flow fractionation (AsPFF) separation systems to evaluate their purification efficiencies considering operation parameters such as the Flow Rate Ratio (FRR) and Total Velocity Ratio (TVR). Additionally, a mixture interaction approach was used to model the MNPs as a dispersed ferrofluid phase. This was compared with a particle tracing approach where MNPs are considered individual entities subjected to hydrodynamic forces. The results show efficiencies between 60% and 90% for both separation methods, which confirms their feasibility to improve and optimize the purification of MLs in a high throughput manner.

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“…Currently, MLPs have been explored as drug delivery carriers to treat conditions as diverse as cancer, Parkinson's, and Alzheimer's [24][25][26]. Over the past few years, several techniques have been proposed for preparing MLPs, in which nanoparticles can be encapsulated in the aqueous lumen, embedded in the lipid bilayer, or conjugated on the surface of the liposome [27][28][29][30]. By implementing these techniques, liposome solutions' parameters vary considerably, posing some challenges related to their particle size, dispersity, lamellarity, entrapment efficiency, and, most importantly, the difficulty in separating the non-encapsulated/unbound MNPs [31,32].…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Synthesis and Purification of Magnetoliposomes for Potential Applications in the Gastrointestinal Delivery of Difficult-to-Transport Drugs

Torres

¹

,

Cifuentes

²

,

Gómez

³

et al. 2022

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Magnetite nanoparticles (MNPs) have gained significant attention in several applications for drug delivery. However, there are some issues related to cell penetration, especially in the transport of cargoes that show limited membrane passing. A widely studied strategy to overcome this problem is the encapsulation of the MNPs into liposomes to form magnetoliposomes (MLPs), which are capable of fusing with membranes to achieve high delivery rates. This study presents a low-cost microfluidic approach for the synthesis and purification of MLPs and their biocompatibility and functional testing via hemolysis, platelet aggregation, cytocompatibility, internalization, and endosomal escape assays to determine their potential application in gastrointestinal delivery. The results show MLPs with average hydrodynamic diameters ranging from 137 ± 17 nm to 787 ± 45 nm with acceptable polydispersity index (PDI) values (below 0.5). In addition, we achieved encapsulation efficiencies between 20% and 90% by varying the total flow rates (TFRs), flow rate ratios (FRRs), and MNPs concentration. Moreover, remarkable biocompatibility was attained with the obtained MLPs in terms of hemocompatibility (hemolysis below 1%), platelet aggregation (less than 10% with respect to PBS 1×), and cytocompatibility (cell viability higher than 80% in AGS and Vero cells at concentrations below 0.1 mg/mL). Additionally, promising delivery results were obtained, as evidenced by high internalization, low endosomal entrapment (AGS cells: PCC of 0.28 and covered area of 60% at 0.5 h and PCC of 0.34 and covered area of 99% at 4 h), and negligible nuclear damage and DNA condensation. These results confirm that the developed microfluidic devices allow high-throughput production of MLPs for potential encapsulation and efficient delivery of nanostructured cell-penetrating agents. Nevertheless, further in vitro analysis must be carried out to evaluate the prevalent intracellular trafficking routes as well as to gain a detailed understanding of the existing interactions between nanovehicles and cells.

show abstract

In Silico Analysis of Microfluidic Systems for the Purification of Magnetoliposomes

Torres

¹

,

Aranguren

²

,

Reyes

³

et al. 2020

The 2nd International Online-Conference on Nanomaterials

0

View full text Add to dashboard Cite

Magnetite nanoparticles (MNPs) have been considered for several applications in drug delivery. However, the main challenge is to assure high cell-penetration levels, especially when dealing with cargoes that show limited membrane passing. A strategy is to encapsulate the MNPs into liposomes to form magnetoliposomes (MLs) capable of fusing with membranes to achieve high delivery rates. MLs have therefore been used as carriers in the biomedical field due to their ability to release active molecules that can be used in treatments of diverse diseases. There are several techniques to produce such encapsulates, however, the main challenge is that the process often leads to an important fraction of non-encapsulated MNPs. Purification of such a fraction is challenging because of the small size difference between the particles and the MLs and the reduced magnetic responsiveness. Seeking to obtain pure MLs with potential use in the medical field, the following study presents finite element simulations using COMSOL Multiphysics of two purification methods. Accordingly, we implemented the magnetic and asymmetric pinched flow fractionation (AsPFF) separation systems to evaluate their purification efficiencies considering operation parameters such as the Flow Rate Ratio (FRR) and Total Velocity Ratio (TVR). Additionally, a mixture interaction approach was used to model the MNPs as a dispersed ferrofluid phase. This was compared with a particle tracing approach where MNPs are considered individual entities subjected to hydrodynamic forces. The results show efficiencies between 60% and 90% for both separation methods, which confirms their feasibility to improve and optimize the purification of MLs in a high throughput manner.

show abstract

Magnetoliposomes for dual cancer therapy

Cited by 4 publications

References 123 publications

In Silico Analysis of Microfluidic Systems for the Purification of Magnetoliposomes

In Silico Analysis of Microfluidic Systems for the Purification of Magnetoliposomes

Microfluidic Synthesis and Purification of Magnetoliposomes for Potential Applications in the Gastrointestinal Delivery of Difficult-to-Transport Drugs

In Silico Analysis of Microfluidic Systems for the Purification of Magnetoliposomes

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