Pulmonary delivered polymeric micelles – Pharmacokinetic evaluation and biodistribution studies

Hu, Xiaoyun; Yang, Fang; Quan, Li-Hui; Liu, Chunyu; Liu, Xinmin; Ehrhardt, Carsten; Liao, Yong-Hong

doi:10.1016/j.ejpb.2014.10.010

Cited by 44 publications

(11 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After intratracheal dosing, the animals were held in an upright position for 1 minute to ensure delivery of the dose following the removal of the delivery device. 28 …”

Section: Methodsmentioning

confidence: 99%

Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

Ji¹,

Yu²,

Liu³

et al. 2016

DDDT

View full text Add to dashboard Cite

Naringenin (NRG), a flavonoid compound, had been reported to exhibit extensive pharmacological effects, but its water solubility and oral bioavailability are only~46±6 µg/mL and 5.8%, respectively. The purpose of this study is to design and develop NRG-loaded solid lipid nanoparticles (NRG-SLNs) to provide prolonged and sustained drug release, with improved stability, involving nontoxic nanocarriers, and increase the bioavailability by means of pulmonary administration. Initially, a group contribution method was used to screen the best solid lipid matrix for the preparation of SLNs. NRG-SLNs were prepared by an emulsification and low-temperature solidification method and optimized using an orthogonal experiment approach. The morphology was examined by transmission electron microscopy, and the particle size and zeta potential were determined by photon correlation spectroscopy. The total drug content of NRG-SLNs was measured by high-performance liquid chromatography, and the encapsulation efficiency (EE) was determined by Sephadex gel-50 chromatography and high-performance liquid chromatography. The in vitro NRG release studies were carried out using a dialysis bag. The best cryoprotectant to prepare NRG-SLN lyophilized powder for future structural characterization was selected using differential scanning calorimetry, powder X-ray diffraction, and Fourier transform infrared spectroscopy. The short-term stability, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay, cellular uptake, and pharmacokinetics in rats were studied after pulmonary administration of NRG-SLN lyophilized powder. Glycerol monostearate was selected to prepare SLNs, and the optimal formulation of NRG-SLNs was spherical in shape, with a particle size of 98 nm, a polydispersity index of 0.258, a zeta potential of −31.4 mV, a total drug content of 9.76 mg, an EE of 79.11%, and a cumulative drug release of 80% in 48 hours with a sustained profile. In addition, 5% mannitol (w/v) was screened as a cryoprotectant. Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffraction studies confirmed that the drug was encapsulated into SLNs in an amorphous form. The lyophilized powder was stable at both refrigeration (4°C) and ambient temperature (25°C) for 3 months, and the MTT assay demonstrated that the SLNs were nontoxic. The cellular uptake of fluorescein isothiocyanate-labeled SLNs in A549 cells was highly time dependent over a period of 3 hours, while the pharmacokinetic study in Sprague Dawley rats showed that the relative bioavailability of NRG-SLNs was 2.53-fold greater than that of NRG suspension after pulmonary administration. This study shows that SLNs offer a promising pulmonary delivery system to increase the bioavailability of the poorly water-soluble drug NRG.

show abstract

“…After intratracheal dosing, the animals were held in an upright position for 1 minute to ensure delivery of the dose following the removal of the delivery device. 28 …”

Section: Methodsmentioning

confidence: 99%

Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

Ji¹,

Yu²,

Liu³

et al. 2016

DDDT

View full text Add to dashboard Cite

show abstract

“…However, despite the amount of research on polymeric micelles, data regarding the uptake mechanisms and intracellular trafficking of these micelles remains behind. Furthermore, most research that investigated the endocytic uptake of polymeric micelles only analyzed the uptake of the drug, hence, only providing indirect evidence for nanocarrier uptake [47,[93][94][95][96][97][98][99][100][101]. As will be discussed below, this assumption may not always be correct, as the carrier and the load can separate upon the uptake.…”

Section: Uptake Mechanisms Of Polymeric Micellesmentioning

confidence: 99%

“…PEG 2000 -b-PLGA 5000 micelles were previously created by Hu et al [98] and the uptake in Calu-3 or NCI-H441 cells investigated [99]. After an incubation of one hour, the drug was observed in the cytosol.…”

Section: Peg-b-plgamentioning

confidence: 99%

Drug Delivery with Polymeric Nanocarriers—Cellular Uptake Mechanisms

2020

View full text Add to dashboard Cite

Nanocarrier-based systems hold a promise to become “Dr. Ehrlich’s Magic Bullet” capable of delivering drugs, proteins and genetic materials intact to a specific location in an organism down to subcellular level. The key question, however, how a nanocarrier is internalized by cells and how its intracellular trafficking and the fate in the cell can be controlled remains yet to be answered. In this review we survey drug delivery systems based on various polymeric nanocarriers, their uptake mechanisms, as well as the experimental techniques and common pathway inhibitors applied for internalization studies. While energy-dependent endocytosis is observed as the main uptake pathway, the integrity of a drug-loaded nanocarrier upon its internalization appears to be a seldomly addressed problem that can drastically affect the uptake kinetics and toxicity of the system in vitro and in vivo.

show abstract

“…Under TEM, The morphology of PUE@PEG-PE micelles was illustrated in Figure 1(B) , presenting perfectly spheroidal shape and approximately core–shell structure with small size (Tong et al., 2011 ). This might be due to the interparticle electrostatic repulsion which may prevent the aggregation of the vesicles and increase the stability of the dispersions (Hu et al., 2014 ; Szilagyi et al., 2014 ). Average size of blank PEG-PE micelles was 14.2 nm.…”

Section: Resultsmentioning

confidence: 99%

Puerarin-loaded PEG-PE micelles with enhanced anti-apoptotic effect and better pharmacokinetic profile

Zhang

et al. 2018

Drug Delivery

View full text Add to dashboard Cite

Puerarin (PUE) is the most abundant isoflavonoid in kudzu root. It is widely used as a therapeutic agent for the treatment of cardiovascular diseases. However, the short elimination half-life, poor-bioavailability, and acute intravascular hemolysis of PUE are the main obstacles to its widespread clinical applications. Whereas PEG-PE micelles possess the ability to release medicine slowly, enhance the cellular uptake of drugs and improve their biocompatibility. Therefore, it was aim to fabricate puerarin-loaded PEG-PE (PUE@PEG-PE) micelles to improve the pharmaceutical properties of drugs. It can be observed from the TEM images that PUE@PEG-PE micelles appeared obvious core-shell structure and remained well-dispersed without aggregation and adhesion. PUE was successfully embedded in the core of PEG-PE micelles, which was confirmed by FT-IR and 1H NMR spectra. In vitro studies showed that PUE@PEG-PE micelles exhibited a sustained release behavior in pH 7.4 PBS buffer and decreased hemolysis rate of PUE. Compared with PUE, PUE@PEG-PE micelles showed a 3.2-fold increase in the half-life of PUE and a 1.58-fold increase in bioavailability. In addition, the PUE@PEG-PE micelles exerted enhanced protective effect against isoprenaline-induced H9c2 cells apoptosis compared with PUE, as evident by decreased percentage of Hoechst-positive cells, Caspase 3 activity, Bax expression, and increased Bcl-2 expression. Notably, the PEG-PE micelles exhibited favorable cellular uptake efficiency on H9c2 cells, and this may account for their enhanced anti-apoptotic effect of the incorporated drug. Altogether, the PUE@PEG-PE micelles were not only able to control the drug release but also offered promise to enhance the pharmacokinetic and pharmacodynamic potential of PUE.

show abstract

Pulmonary delivered polymeric micelles – Pharmacokinetic evaluation and biodistribution studies

Cited by 44 publications

References 49 publications

Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

Naringenin-loaded solid lipid nanoparticles: preparation, controlled delivery, cellular uptake, and pulmonary pharmacokinetics

Drug Delivery with Polymeric Nanocarriers—Cellular Uptake Mechanisms

Puerarin-loaded PEG-PE micelles with enhanced anti-apoptotic effect and better pharmacokinetic profile

Contact Info

Product

Resources

About