Microfluidic Synthesis of PEG- and Folate-Conjugated Liposomes for One-Step Formation of Targeted Stealth Nanocarriers

Hood, Renee R.; Shao, Chenren; Omiatek, Donna M.; Vreeland, Wyatt N.; DeVoe, Don L.

doi:10.1007/s11095-013-0998-3

Cited by 61 publications

(40 citation statements)

References 30 publications

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“…In this method, folate conjugated phospholipid are passed through thermoplastic microfluidic device in a controlled laminar flow. This method can produce immunoliposomes in nano size range (90).…”

Section: Immunoliposomesmentioning

confidence: 99%

Liposomal Drug Delivery: A Versatile Platform for Challenging Clinical Applications

et al. 2014

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-Liposomes are lipid based vesicular systems that offer novel platform for versatile drug delivery to target cell. Liposomes were first reported by Bangham and his co-workers in 1964 (1). Since then, liposomes have undergone extensive research with the prime aim to optimize encapsulation, stability, circulation time and target specific drug delivery. Manipulation of a liposome's lipid bilayer and surface decoration with selective ligands has transformed conventional liposomes into adaptable and multifunctional liposomes. Development of liposomes with target specificity provide the prospect of safe and effective therapy for challenging clinical applications. Bioresponsive liposomes offer the opportunity to release payload in response to tissue specific microenvironment. Incorporation of novel natural and synthetic materials has extended their application from stable formulations to controlled release targeted drug delivery systems. Integration and optimization of multiple features into one system revolutionized research in the field of cancer, gene therapy, immunotherapy and infectious diseases. After 50 years since the first publication, this review is aimed to highlight next generation of liposomes, their preparation methods and progress in clinical applications.

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Section: Immunoliposomesmentioning

confidence: 99%

Liposomal Drug Delivery: A Versatile Platform for Challenging Clinical Applications

et al. 2014

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“…Subsequently, these lipid discs bend to reduce the exposure of the hydrophobic lipid chain to the hydrophilic buffer and finally close into spherical liposomes [11]. This single-step method offers better control over the properties of liposomes, such as particle size, size distribution and surface properties (PEGylation and targeting ligand) [11][12][13][14]. More importantly, this method can be easily scaled up.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic synthesis of multifunctional liposomes for tumour targeting

Ran

Middelberg

Zhao

2016

Colloids and Surfaces B: Biointerfaces

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Graphical abstract Highlights Targeted liposomes can be prepared in the one-step microfluidic device  Size and surface properties can be controlled easily  This microfluidic method directed targeted liposomes possess selective cell uptake enhancement in both 2D and 3D model.  At the same time, these liposomes can reduce phagocytosis. AbstractNanotechnology has started a new era in engineering multifunctional nanoparticles for diagnosis and therapeutics by incorporating therapeutic drugs, targeting ligands, stimuliresponsive release and imaging molecules. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield and high production cost, hence difficulties in clinical translation. Herein we report a one-step microfluidic method for making multifunctional liposomes. Three formulations were prepared using this simple method, including plain liposomes, PEGylated liposomes and folic acid functionalised liposomes, all with a fluorescence dye encapsulated for imaging. The size and surface properties of these liposomes can be precisely controlled by simply tuning the flow rate ratio and the ratio of the lipids to PEGylated lipid (DSPE-PEG2000) and to the DSPE-PEG2000-Folate, respectively. The synthesised liposomes remained stable under mimic serum conditions.Compared to the plain liposomes and PEGylated liposomes, the targeted folic acid functionalised liposomes exhibited enhanced cellular uptake by the FA receptor positive SKOV3 cells, but not the negative MCF7 cells, and this enhanced uptake could be inhibited by adding excess free folic acid, indicating high specificity of FA ligand-receptor endocytosis.Further evaluation using the 3D tumour spheroid model also showed higher internalisation of the targeted liposome formulation in comparison with the PEGylated one. To the best of our knowledge, this work demonstrates for the first time the versatility of this microfluidic method for making different liposome formulations in a single step, their superior physicochemical properties as well as the enhanced cellular uptake and tumour spheroid uptake of the targeted liposomes.

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“…Moreover, we found that TUNEL experiments showed apoptotic death of SW480 cells was also consistently increased. PEG-liposomal L-OHP degraded in cells after pinocytosis; furthermore, the intracellular drug release enhanced active drug level within cells and slowed down drug efflux, therefore, liposome entrapment of chemotherapeutics represents its dual effect on tumor cells (24)(25)(26).…”

Section: Discussionmentioning

confidence: 99%

PEG-liposomal oxaliplatin combined with nuclear factor-κB inhibitor (PDTC) induces apoptosis in human colorectal cancer cells

Yang

2014

Oncology Reports

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To achieve sufficient antitumor activity for colorectal carcinoma, optimization of the therapeutic regimen is of great importance. The aim of the present study was to investigate the effects of polyethylene glycol (PEG)-liposomal oxaliplatin (L-OHP) on the induction of apoptosis in human colorectal cancer SW480 cells and how the nuclear factor-κB (NF-κB) pathway may contribute to mediating PEG-liposomal L-OHP-induced apoptosis. PEG-liposomal L-OHP was prepared and used to treat colorectal cancer SW480 cells. SW480 cell uptake of liposomes was observed by laser focus or SEM. Apoptosis was measured by flow cytometry (FCM) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assay. Expression of NF-κB, Bcl-2, Bax and activated caspase-3 (P17) was examined by western blot analyses. The results indicated that PEG-liposomal L-OHP induced apoptosis. When pretreated with pyrrolidine dithiocarbamate (PDTC), PEG-liposomal L-OHP induced a significant apoptotic response. Moreover, apoptosis was associated with concentration of PDTC. Expression of protein p-P65, Bcl-2 was downregulated, but Bax and P17 were upregulated. These findings indicate that PEG-liposomal L-OHP enhances the anticancer potency of the chemotherapeutic agent. Moreover, NF-κB signaling pathways may contribute to mediating PEG-liposomal L-OHP-induced apoptosis.

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Microfluidic Synthesis of PEG- and Folate-Conjugated Liposomes for One-Step Formation of Targeted Stealth Nanocarriers

Cited by 61 publications

References 30 publications

Liposomal Drug Delivery: A Versatile Platform for Challenging Clinical Applications

Liposomal Drug Delivery: A Versatile Platform for Challenging Clinical Applications

Microfluidic synthesis of multifunctional liposomes for tumour targeting

PEG-liposomal oxaliplatin combined with nuclear factor-κB inhibitor (PDTC) induces apoptosis in human colorectal cancer cells

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