Chylomicron-pretended nano-bio self-assembling vehicle to promote lymphatic transport and GALTs target of oral drugs

Mao, Yuling; Feng, Shuang; Li, Shuai; Zhao, Qinfu; Di, Donghua; Liu, Yanfeng; Wang, Siling

doi:10.1016/j.biomaterials.2018.10.012

Cited by 45 publications

(32 citation statements)

References 50 publications

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“…Lipids are naturally packaged into chylomicron particles by enterocytes, which are transported to systemic circulation via lymphatic vessels. Nanoparticles can be formulated to mimic chylomicrons through the addition of lipids or bile salts on the surface [27][28][29][30][31]. For example, one group generated 100 nm mesoporous silica nanoparticles coated with 1,3-dipalmitoyl-glycerols with a ζ-potential of -8.3…”

Section: Discussionmentioning

confidence: 99%

“…mV, and demonstrated that these nanoparticles entered the lymphatics through the chylomicron pathways after oral administration [27]. Studies using glycocholic acid-(a bile salt) conjugated 100 nm nanoparticles demonstrated that these nanoparticles improved lymphatic delivery of therapeutics including paclitaxel, insulin, and Exendin-4 compared to uncoated nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

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Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

McCright

Skeen

Yarmovsky

et al. 2020

Preprint

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Lymphatic vessels have received considerable attention in recent years as delivery route for immune modulatory therapies to the lymph nodes. Lymph node targeting of immunotherapies and vaccines has been shown to significantly enhance their therapeutic efficacy. Lymphatics transport functions materials from peripheral tissues to the lymph nodes, including small 10 – 250 nm therapeutic nanoparticles. While size required to enter lymphatic vessels, surface chemistry is more poorly studied. Here, we probed the effects of surface poly(ethylene glycol) (PEG) density on nanoparticle transport across lymphatic endothelial cells (LECs). We differentially PEGylated model carboxylate-modified polystyrene nanoparticles to form either a brush or dense brush PEG conformation on the nanoparticle surfaces. Using an established in-vitro lymphatic transport model, we found that the addition of any PEG improved the transport of nanoparticles through lymphatic endothelial cells (2.5 - 2.6 ± 0.9% transport efficiency at 24 hours) compared to the unmodified PS-COOH nanoparticles (0.05 ± 0.05% transport efficiency at 24 hours). Additionally, we found that transcellular transport is maximized (4.2 ± 0.7% transport efficiency at 24 hours) when the PEG is in a dense brush conformation on nanoparticle surfaces, corresponding with a high grafting density (Rf/D = 4.9). These results suggest that PEG conformation has a crucial role in determining translocation of nanoparticles across LECs and into lymphatic vessels. Thus, we identified PEG density as a major design criteria for maximizing lymphatic targeting of therapeutic nanoparticle formulations that can be widely applied to enhance immunotherapeutic and vaccine outcomes in future studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

McCright

Skeen

Yarmovsky

et al. 2020

Preprint

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“…The NPs improved poor solubility and avoided the first-pass metabolism of oral lopinavir to achieve high oral bioavailability with no side effects. 147 The lopinavir-loaded bioadhesive protein NPs increased the oral bioavailability by 4-and 1.5-fold compared to the free lopinavir suspension and lopinavir/ritonavir formulations, respectively. 140 The poly (lactic-co-glycolic acid) NPs increased the permeability and oral bioavailability of lopinavir by 3.04-and 13.9-fold in rats.…”

Section: Nanotechnology To Improve Pharmacokinetics Of Avds Delivery System To Improve Pharmacokineticsmentioning

confidence: 98%

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

Chen¹,

Wang²,

Song³

et al. 2021

IJN

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Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 . Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.

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“…A cytotoxicity assay of GSN was performed using a plate reader (DNM-9606) at 492 nm. 21 GSN (100 mg) were dispersed at 1 mg/mL of fluorescein isothiocyanate (FITC) anhydrous ethanol solution under stirring for 4 h, and then FITC-labeled GSN (FITC-GSN) were obtained by centrifugation. The sample was stored in a vacuum.…”

Section: Gsn Cytotoxicity Cell Uptake and Intestinal Mucosal Uptakementioning

confidence: 99%

Development and Characterization of a Glimepiride-Loaded Gelatin-Coated Mesoporous Hollow Silica Nanoparticle Formulation and Evaluation of Its Hypoglycemic Effect on Type-2 Diabetes Model Rats

Liu

Lin

2020

ASSAY and Drug Development Technologies

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In this study, we prepared gelatin-coated mesoporous hollow silica nanospheres (GSN) as a drug carrier to improve the water solubility and regulate the release rate of glimepiride (GLM). GLM was loaded into GSN by an absorption method, and drugloaded samples (GLM-GSN) were characterized by differential scanning calorimeter (DSC) and X-ray diffraction (XRD). Cellular uptake and in vivo intestinal uptake experiments were performed in rats. In addition, the studies of in-vitro drug dissolution, pharmacokinetics, and pharmacodynamic experiments also were performed. GLM-GSN showed excellent drug loading (39.7%-0.7%) and sustained GLM release. The state of GLM in GSN was amorphous according to DSC and XRD results. Cellular uptake and in vivo intestinal uptake experiments indicated that GSN could be effectively absorbed, and an MTT experiment demonstrated that GSN had good biocompatibility. Furthermore, the GLM-GSN had a higher bioavailability in pharmacokinetics experiments and a prominent hypoglycemic effect on type-2 diabetes model rats in pharmacodynamic experiments. This study clearly shows that GSN is a promising platform for delivering GLM for the treatment of type-2 diabetes.

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Chylomicron-pretended nano-bio self-assembling vehicle to promote lymphatic transport and GALTs target of oral drugs

Cited by 45 publications

References 50 publications

Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

Dense poly(ethylene glycol) coatings maximize nanoparticle transport across lymphatic endothelial cells and accumulate in the skindraining lymph nodes

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

Development and Characterization of a Glimepiride-Loaded Gelatin-Coated Mesoporous Hollow Silica Nanoparticle Formulation and Evaluation of Its Hypoglycemic Effect on Type-2 Diabetes Model Rats

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