Abstract:Illustration of the Zapped Assembly of Polymeric (ZAP) nanoparticles processing by the microwave heating of PLGA-PEG, PLGA, TPGS, and PXL in solvent followed by cooling to produce nanoparticles with exceptionally high loading of PXL (12.6 wt%, ∼7 times higher than the original PLGA-PEG NPs).
“…The blank blend NPs at 114 nm showed no toxicity from 0.1 μg/mL to 100 μg/mL, while the 45 nm blank blend NPs showed some toxicity to HeLa cells at higher concentrations. It has been previously reported that nano-sized PLGA particles can be toxic to cells to some extent [ 36 , 37 ]. After incubation with 52 nm blend-PTX for 24 h, cell viability remarkably reduced, whereas 109 nm blend-PTX could not show significant cytotoxicity.…”
The realization of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) from laboratory to clinical applications remains slow, partly because of the lack of precise control of each condition in the preparation process and the rich selectivity of nanoparticles with diverse characteristics. Employing PLGA NPs to establish a large range of size-controlled drug delivery systems and achieve size-selective drug delivery targeting remains a challenge for therapeutic development for different diseases. In this study, we employed a microfluidic device to control the size of PLGA NPs. PLGA, poly (ethylene glycol)-methyl ether block poly (lactic-co-glycolide) (PEG-PLGA), and blend (PLGA + PEG-PLGA) NPs were engineered with defined sizes. Blend NPs exhibit the widest size range (40–114 nm) by simply changing the flow rate conditions without changing the precursor (polymer molecular weight, concentration, and chain segment composition). A model hydrophobic drug, paclitaxel (PTX), was encapsulated in the NPs, and the PTX-loaded NPs maintained a large range of controllable NP sizes. Furthermore, size-controlled NPs were used to investigate the effect of particle size of sub-200 nm NPs on tumor cell growth. The 52 nm NPs showed higher cell growth inhibition than 109 nm NPs. Our method allows the preparation of biodegradable NPs with a large size range without changing polymer precursors as well as the nondemanding fluid conditions. In addition, our model can be applied to elucidate the role of particle sizes of sub-200 nm particles in various biomedical applications, which may help develop suitable drugs for different diseases.
“…The blank blend NPs at 114 nm showed no toxicity from 0.1 μg/mL to 100 μg/mL, while the 45 nm blank blend NPs showed some toxicity to HeLa cells at higher concentrations. It has been previously reported that nano-sized PLGA particles can be toxic to cells to some extent [ 36 , 37 ]. After incubation with 52 nm blend-PTX for 24 h, cell viability remarkably reduced, whereas 109 nm blend-PTX could not show significant cytotoxicity.…”
The realization of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) from laboratory to clinical applications remains slow, partly because of the lack of precise control of each condition in the preparation process and the rich selectivity of nanoparticles with diverse characteristics. Employing PLGA NPs to establish a large range of size-controlled drug delivery systems and achieve size-selective drug delivery targeting remains a challenge for therapeutic development for different diseases. In this study, we employed a microfluidic device to control the size of PLGA NPs. PLGA, poly (ethylene glycol)-methyl ether block poly (lactic-co-glycolide) (PEG-PLGA), and blend (PLGA + PEG-PLGA) NPs were engineered with defined sizes. Blend NPs exhibit the widest size range (40–114 nm) by simply changing the flow rate conditions without changing the precursor (polymer molecular weight, concentration, and chain segment composition). A model hydrophobic drug, paclitaxel (PTX), was encapsulated in the NPs, and the PTX-loaded NPs maintained a large range of controllable NP sizes. Furthermore, size-controlled NPs were used to investigate the effect of particle size of sub-200 nm NPs on tumor cell growth. The 52 nm NPs showed higher cell growth inhibition than 109 nm NPs. Our method allows the preparation of biodegradable NPs with a large size range without changing polymer precursors as well as the nondemanding fluid conditions. In addition, our model can be applied to elucidate the role of particle sizes of sub-200 nm particles in various biomedical applications, which may help develop suitable drugs for different diseases.
“…Under this condition, the encapsulation efficiency reached as high as 87.60 ± 8.73% (Figure S5), and the particle size was 161.61 ± 15.63 nm, which was favorable, as large particle (> 200 nm) could be cleared by RES. 31 Figure 4 Preparation and characterization of pSFV-MEG/LNPs. (A) Structural diagram of pSFV-MEG/LNPs.…”
DNA vaccine is an attractive immune platform for the prevention and treatment of infectious diseases, but existing disadvantages limit its use in preclinical and clinical assays, such as weak immunogenicity and short half-life. Here, we reported a novel liposome-polymer hybrid nanoparticles (pSFV-MEG/LNPs) consisting of a biodegradable core (mPEG-PLGA) and a hydrophilic shell (lecithin/PEG-DSPE-Mal 2000) for delivering a multi-epitope self-replication DNA vaccine (pSFV-MEG). The pSFV-MEG/LNPs with optimal particle size (161.61 ± 15.63 nm) and high encapsulation efficiency (87.60 ± 8.73%) induced a strong humoral (3.22-fold) and cellular immune responses (1.60-fold) compared to PBS. Besides, the humoral and cellular immune responses of pSFV-MEG/LNPs were 1.58- and 1.05-fold than that of pSFV-MEG. All results confirmed that LNPs were a very promising tool to enhance the humoral and cellular immune responses of pSFV-MEG. In addition, the rational design and delivery platform can be used for the development of DNA vaccines for other infectious diseases.
“…PEG-PLGA NPs have emerged as a novel formulation with great biocompatibility and non-immunogenicity that can improve the solubility, stability, and safety of chemotherapeutic drugs for the treatment of various cancer types (Table 1). For example, paclitaxel (PTX)-loaded PEG-PLGA NPs rapidly prepared by microwave synthesis showed similar cytotoxicity to Taxol (Dunn et al, 2019). Satisfactory pharmacokinetic and pharmacodynamic results have also been reported for docetaxel Frontiers in Pharmacology frontiersin.org (DTX)-and PTX-loaded PEG-PLGA NPs (Wei et al, 2013;Noori Koopaei et al, 2014).…”
Section: Chemotherapeutic Applicationsmentioning
confidence: 94%
“…PEGylating recombinant human interleukin-11 (IL-11) not only enhanced its pharmacological activity, but also prolonged its retention time in plasma by reducing the liver and kidney clearance of IL-11 (Takagi et al, 2007) (Menkhorst et al, 2009). Modifying PLGA NPs with PEG improves their surface hydrophilicity and prolongs circulation time (Noori Frontiers in Pharmacology frontiersin.org Koopaei et al, 2014), giving them substantial promise as drug carriers (Haggag et al, 2018;Dunn et al, 2019). These NPs consist of a PEG shell and a PLGA core that can effectively encapsulate hydrophilic and hydrophobic drugs (Figure 2).…”
Nanoparticles based on single-component synthetic polymers, such as poly (lactic acid-co-glycolic acid) (PLGA), have been extensively studied for antitumor drug delivery and adjuvant therapy due to their ability to encapsulate and release drugs, as well as passively target tumors. Amphiphilic block co-polymers, such as polyethylene glycol (PEG)-PLGA, have also been used to prepare multifunctional nanodrug delivery systems with prolonged circulation time and greater bioavailability that can encapsulate a wider variety of drugs, including small molecules, gene-targeting drugs, traditional Chinese medicine (TCM) and multi-target enzyme inhibitors, enhancing their antitumor effect and safety. In addition, the surface of PEG-PLGA nanoparticles has been modified with various ligands to achieve active targeting and selective accumulation of antitumor drugs in tumor cells. Modification with two ligands has also been applied with good antitumor effects, while the use of imaging agents and pH-responsive or magnetic materials has paved the way for the application of such nanoparticles in clinical diagnosis. In this work, we provide an overview of the synthesis and application of PEG-PLGA nanoparticles in cancer treatment and we discuss the recent advances in ligand modification for active tumor targeting.
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