scholarly journals LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque

Author(s):  
Christian A. Boada ◽  
Assaf Zinger ◽  
Scott Rohen ◽  
Jonathan O. Martinez ◽  
Michael Evangelopoulos ◽  
...  

Apolipoprotein-based drug delivery is a promising approach to develop safe nanoparticles capable of targeted drug delivery for various diseases. In this work, we have synthesized a lipid-based nanoparticle (NPs) that we have called “Aposomes” presenting native apolipoprotein B-100 (apoB-100), the primary protein present in Low-Density Lipoproteins (LDL) on its surface. The aposomes were synthesized from LDL isolated from blood plasma using a microfluidic approach. The synthesized aposomes had a diameter of 91 ± 4 nm and a neutral surface charge of 0.7 mV ± mV. Protein analysis using western blot and flow cytometry confirmed the presence of apoB-100 on the nanoparticle’s surface. Furthermore, Aposomes retained liposomes’ drug loading capabilities, demonstrating a prolonged release curve with ∼80% cargo release at 4 hours. Considering the natural tropism of LDL towards the atherosclerotic plaques, we evaluated the biological properties of aposomes in a mouse model of advanced atherosclerosis. We observed a ∼20-fold increase in targeting of plaques when comparing aposomes to control liposomes. Additionally, aposomes presented a favorable biocompatibility profile that showed no deviation from typical values in liver toxicity markers (i.e., LDH, ALT, AST, Cholesterol). The results of this study demonstrate the possibilities of using apolipoprotein-based approaches to create nanoparticles with active targeting capabilities and could be the basis for future cardiovascular therapies.

2019 ◽  
Author(s):  
Yuan Chuanxun ◽  
Zhang Xueru ◽  
Jin Risheng

AbstractThe aim of this study is to develop a self microemulsion drug delivery system for phytosterols to improve the solubility and bioavailability. The results showed that the formulation of phytosterol self-microemulsion is: lemon essential oil in oil phase, polyoxyethylene hydrogenated castor oil 40 and Tween 60 in emulsifier, polyethylene glycol 400 in co-emulsifier, Km = 7:3, Kp = 3:1, Ke = 50%. The drug loading of phytosterol self-microemulsion prepared by this method was 87.22 mg/g, encapsulation efficiency was 89.65%, particle size was 48.85nm, potential was −12.863mV. In vitro release experiment showed that the release of phytosterols in microemulsion was more than 90%, and the release curve was in accordance with the first-order kinetics equation. The pharmacokinetic analysis of PSSM synthesized by this method shows that PSSM can increase the bioavailability of PS more than three times, so it is necessary to do more in-depth research on the self-microemulsion delivery system of phytosterols.


2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Zhaohui Li ◽  
Congqin Ning ◽  
Dongyan Ding ◽  
Hegang Liu ◽  
Lin Huang

Surface modification of low modulus implant alloys with oxide nanostructures is one of the important ways to achieve favorable biological behaviors. In the present work, amorphous Ti-Nb-Zr-O nanostructures were grown on a peak-aged Ti35Nb5Zr alloy through anodization. Biological properties of the Ti-Nb-Zr-O nanostructures were investigated throughin vitrobioactivity testings, stem cell interactions, and drug release experiments. The Ti-Nb-Zr-O nanostructures demonstrated a good capability of inducing apatite formation after immersion in simulated body fluids (SBFs). Drug delivery experiment based on gentamicin and the Ti-Nb-Zr-O nanostructures indicated that a high drug loading content could result in a prolonged release process and a higher quantity of drug residues in the oxide nanostructures after drug release. Quick stem cell adhesion and spreading, as well as fast formation of extracellular matrix materials on the surfaces of the Ti-Nb-Zr-O nanostructures, were found. These findings make it possible to further explore the biomedical applications of the Ti-Nb-Zr-O nanostructure modified alloys especially clinical operation of orthopaedics by utilizing the nanostructures-based drug-release system.


2020 ◽  
Vol 10 (2) ◽  
pp. 166-183 ◽  
Author(s):  
Dipak Dilip Gadade ◽  
Sanjay Sudhakar Pekamwar

Colloidal nanoparticulate technology has been described in the literature as a versatile drug delivery system. But it possesses some inherent lacunae in their formulation. Cyclodextrins (CDs) have been extensively reported for the solubility enhancement of poorly water-soluble drugs. The CDs can cause intervention in aspects related to nanoparticles (NPs) that include improving drug loading in nano-system, improving stability, site-specific/targeted drug delivery, improving solubility profile and absorption of the drug in nanosystem with consequent improvement in bioavailability, with the possibility of controlled release, safety and efficacy. They find application in for simultaneous diagnosis and therapeutics for better treatment procedures. The current communication is focused on the application of CDs to overcome troubles in nanoparticulate formulation and enhancement of their performance. It also envisages the theranostic aspects of CDs.


2014 ◽  
Vol 2 (46) ◽  
pp. 8085-8097 ◽  
Author(s):  
D. M. Eckmann ◽  
R. J. Composto ◽  
A. Tsourkas ◽  
V. R. Muzykantov

Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli.


Nanoscale ◽  
2020 ◽  
Vol 12 (17) ◽  
pp. 9541-9556 ◽  
Author(s):  
Seyedmehdi Hossaini Nasr ◽  
Zahra Rashidijahanabad ◽  
Sherif Ramadan ◽  
Nate Kauffman ◽  
Narayanan Parameswaran ◽  
...  

Atherosclerosis is associated with inflammation in the arteries. Hyaluronan atorvastatin nanoparticle conjugate could target CD44 overexpressed in atherosclerotic plaques and significantly reduce plaque associated inflammation.


Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3082 ◽  
Author(s):  
Wei Liu ◽  
Fan Wang ◽  
Yongchao Zhu ◽  
Xue Li ◽  
Xiaojing Liu ◽  
...  

Targeted drug delivery to colon cancer cells can significantly improve the efficiency of treatment. We firstly synthesized carboxyl-modified mesoporous silica nanoparticles (MSN–COOH) via two-step synthesis, and then developed calcium leucovorin (LV)-loaded carboxyl-modified mesoporous silica nanoparticles based on galactosylated chitosan (GC), which are galectin receptor-mediated materials for colon-specific drug delivery systems. Both unmodified and functionalized nanoparticles were characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD), Fourier transform infrared (FT-IR), nitrogen sorption, and dynamic light scattering (DLS). Drug release properties and drug loading capacity were determined by ultraviolet spectrophotometry (UV). LV@MSN–COOH/GC had a high LV loading and a drug loading of 18.07%. In vitro, its release, mainly by diffusion, was sustained release. Cell experiments showed that in SW620 cells with the galectin receptor, the LV@MSN–COOH/GC metabolized into methyl tetrahydrofolic acid (MTHF) and 5-fluorouracil (5-FU)@MSN–NH2/GC metabolized into FdUMP in vivo. MTHF and 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) had combined inhibition and significantly downregulated the expression of thymidylate synthase (TS). Fluorescence microscopy and flow cytometry experiments show that MSN–COOH/GC has tumor cell targeting, which specifically recognizes and binds to the galectin receptor in tumor cells. The results show that the nano-dosing system based on GC can increase the concentrations of LV and 5-FU tumor cells and enhance their combined effect against colon cancer.


RSC Advances ◽  
2021 ◽  
Vol 11 (31) ◽  
pp. 18809-18817
Author(s):  
Ali Bina ◽  
Heidar Raissi ◽  
Hassan Hashemzadeh ◽  
Farzaneh Farzad

Polymeric nanoparticles have emerged as efficient carriers for anticancer drug delivery because they can improve the solubility of hydrophobic drugs and also can increase the bio-distribution of drugs throughout the bloodstream.


Carbon ◽  
2012 ◽  
Vol 50 (2) ◽  
pp. 622-632 ◽  
Author(s):  
Elena Heister ◽  
Vera Neves ◽  
Constanze Lamprecht ◽  
S.Ravi P. Silva ◽  
Helen M. Coley ◽  
...  

2018 ◽  
Vol 8 (6-s) ◽  
pp. 328-339 ◽  
Author(s):  
Ankita Gupta ◽  
Shaifali Dubey ◽  
Mayuri Mishra

Dendrimers are novel three dimensional, hyperbranched globular nano polymeric architectures. Attractive features like nanoscopic size, narrow polydispersity index and excellent control over molecular structure afford dendrimers with ideal drug delivery ability through encapsulating drugs in their interior or covalently conjugating drugs on their surfaces. The adaptable surface functionalization ability enables covalent conjugation of various targeting molecules onto the surface of dendrimers, thereby allowing for generation of various multifunctional nanodevices for targeted drug delivery applications. Drug delivery researchers are especially enthusiastic about possible utility of dendrimers as drug delivery tool. However, to get the maximum benefits of these novel class macromolecules, a research by collaboration is very much essential. Finally,  it is one of the youngest and exciting fields of polymer researches where all branches of science can take part and hence, deserves more intensive attention. Keywords: Dendrimers, Drug Delivery, Targeting, Dual Drug Loading, PAMAM


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