Increase in the Vascular Residence Time of Propranolol-Loaded Nanoparticles Coated with Heparin (original) (raw)
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Preparation and In Vitro Evaluation of Heparin-Loaded Polymeric Nanoparticles
Drug Delivery, 2001
Nanoparticles of a highly soluble macromolecular drug, heparin, were formulated with two biodegradable polymers (poly-ecaprolactone [PCL] and poly (D, L-lactic-co-glycolic-acid) 50/50 [PLAGA]) and two nonbiodegradabl e positively charged polymers (Eudragit RS and RL) by the double emulsion and solvent evaporation method, using a high-pressure homogenization device. The encapsulation ef ciency and heparin release pro les were studied as a function of the type of polymers employed (alone or in combination) and the concentration of heparin. Optimal encapsulation ef ciency was observed when 5000 IU of heparin were incorporated in the rst emulsion. High drug entrapment ef ciency was observed in both Eudragit RS and RL nanoparticles (60% and 98%, respectively), compared with PLAGA and PCL nanoparticles (<14%). The use of the two types of Eudragit in combination with PCL and PLAGA increased the encapsulation ef ciency compared with these two biodegradable polymers used alone; however, the in vitro drug release was not modi ed and remained low. On the other hand, the addition of esterase to the dissolution medium resulted in a signi cant increase in heparin release. The in vitro biological activity of released heparin, evaluated by measuring the anti-Xa activity by a colorimetric assay, was conserved after the encapsulation process.
International Journal of Pharmacy and Pharmaceutical Sciences, 2016
Objective: The objective of the current research work was to prepare and evaluate novel subcutaneous sustained release polymeric nanoparticles for low molecular weight heparin (LMWH). Methods: In this study, we prepared subcutaneously administered polymeric nanoparticles encapsulating LMWH using different grades of polycaprolactons (PCL) (14k, 45k, 80k) and 0.1% Polyvinyl alcohol (PVA) solution as surfactant by employing water-in-oil in-water (w/o/w) emulsion and evaporation method. The formulated nanoparticles were evaluated for size, shape, zeta potential, in vitro drug release, and in vivo biological activity (anti factor Xa activity) using standard kit, antithrombotic activity in thrombosis induced rat model. Drug and polymer interactions in the nanoparticles were evaluated using Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD). Results: Scanning electron microscopic (SEM) studies on the nanoparticles confirmed the formation of spherical particles with smooth surface. The size of the formed nanoparticles were about 415-495 nm. The % entrapment of nanoparticles was found to be between 69-81%. Nanoparticles showed slow and sustained pattern of release for about 59-65 % in 48 h. Optimized nanoparticles exhibited excellent improvement in pharmacokinetic parameters and showed good antithrombotic activity, Activated partial thromboplastin time (aPTT) activity when compared to free drug. FTIR studies indicated that there was no loss in chemical integrity of the drug upon fabrication into nanoparticles. XRD results demonstrated that the drug changed its physical form in the formulation. Conclusion: The results of this study revealed that subcutaneous nanoparticles were excellent candidates for sustained drug delivery of LMWH to avoid repeated subcutaneous administration.
Interaction of Nanoparticles with Blood Components and Associated Pathophysiological Effects
Unraveling the Safety Profile of Nanoscale Particles and Materials - From Biomedical to Environmental Applications, 2018
Nanotechnology currently plays a pivotal role in several fields and has enabled substantial advances in a relatively short time. In biomedicine, nanomaterials can be potentially employed as a tool for early diagnosis and an innovative mode of drug delivery. Novel nanomaterials are currently widely manipulated without a full assessment of their potential health risks. It is commonly thought that nanomaterials' first contact with the organism is through the different components of the immune system. However, if the entry route is intravenous, the first contact will be with the blood's components (erythrocytes, platelets, white cells, plasma and complement proteins). The presence of nanomaterials within a dynamic environment such as the bloodstream can produce potential harmful effects following interaction with several blood components. The design of innovative strategies leading to the development of more hemocompatible nanomaterials is also necessary.
Nanomedicine, 2013
Aim: A whole blood assay for evaluating the uptake of nanoparticles into white blood cells in order to close the gap between basic studies in cell culture and pharmacokinetic studies in animals was developed. Materials & methods: After drawing peripheral blood into standard blood collection vials with different anticoagulants, amino- and carboxy-functionalized polymeric styrene nanoparticles were added and uptake was evaluated by flow cytometry. Results: By counterstaining surface markers of leukocytes (e.g., monocytes, neutrophil granulocytes, B or T lymphocytes), investigations of different cell types can be conducted in a single run by flow cytometry. The authors demonstrated that anticoagulation should be done with heparin, and not EDTA, in order to prevent hampering of uptake mechanisms. Conclusion: By using heparinized whole blood, the authors demonstrated differences and usefulness of this assay for screening cellular uptake as it should occur in the bloodstream. Nevertheless...
Cytotoxicity assessment of heparin nanoparticles in NR8383 macrophages
International Journal of Pharmaceutics, 2010
The bioavailability of low molecular weight heparin (LMWH) has been increased by encapsulation in nanoparticles. As a complement to these results, the cytotoxicity and apoptosis induced by LMWH nanoparticles prepared by two methods [nanoprecipitation (NP) and double emulsion (DE)] using Eudragit ® RS (RS) and poly--caprolactone (PCL) have been analysed. Particle sizes varied from 54 to 400 nm with zeta potential values between −65 and +63 mV. Our results showed that the method of nanoparticle preparation affects their properties, especially in terms of drug incorporation and cell tolerance. Cell viability ranged from 6% to 100% depending on the preparation method and physicochemical properties of the particles and the type of toxicity assay. Particle diameter and zeta potential seemed to be the most valuable cytotoxicity markers when cell viability was measured by Trypan blue exclusion and MTT respectively. Nanoparticles prepared by DE were better tolerated than those of NP. LMWH encapsulation into the cationic nanoparticles reduces remarkably their toxicity. Apoptosis evaluation showed activated caspases in exposed cells. However, no nuclear fragmentation was detected in NR8383 cells whatever the tested nanoparticles. DE nanoparticles of RS and PCL can be proposed as a good LMWH delivery system due to their low toxicity (IC 50 ∼ 2.33 and 0.96 mg/mL, respectively).
Asian Journal of Pharmaceutical and Clinical Research, 2017
Objective: The objective of the present study was to prepare and evaluate a novel oral formulation of nanoparticles for the systemic delivery of low molecular weight heparin (LMWH). Methods: Nanoparticles were prepared by polyelectrolyte complexation (PEC) method using polymers sodium alginate and chitosan. Entrapment efficiency of LMWH in nanoparticles was found to be ̴88%. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), X‑ray diffraction (XRD), Scanning electron microscopy (SEM) studies carried for nanoparticles. In vitro release studies were performed for the formulations. Ex vivo permeation studies were performed optimized formulation by using small intestine of rat and in vivo studies were conducted on rat model.Results: In vitro release studies demonstrated that the release of LMWH was negligible in the stomach and high in the small intestine. FTIR has indicated that there is no interaction between the ingredients in nanoparticle. DSC...
Biomaterials, 1993
The biological fate of injected foreign particles is believed to be closely related to their interactions with blood plasma proteins and cells. In order to verify this correlation, we have quantitatively measured protein adsorption and blood retention profiles in rats by using model polystyrene latex nanoparticles. The in vitro interactions of these non-biodegradable particles with plasma proteins and whole blood can be altered by modifying their surfaces with a family of amphiphilic polymeric surfactants, PEO/PPO Pluronic or Tetronic block copolymers. Protein adsorption was measured by several techniques, including photon correlation spectroscopy, centrifugation, high performance liquid chromatography and field-flow fractionation. Pluronic F108 and Tetronic 908 and 1508 copolymers (with PEO terminal block iWpE 0 > 5000, PPO middle block MWpp 0 > 3000, and HLB values >24) were shown to be the most effective surface modifiers in reducing adsorption of plasma proteins on the particles. Minimum interaction of coated particles with whole blood was also observed by optical microscopy. The blood circulation half-life of the particles injected in rats was increased from 20 min to 13 h when the latex particles (75 nm) were precoated with these block copolymers. These results suggest that nanoparticles designed for use as injectable drugs or drug carriers should display similar surface characteristics provided by such amphiphilic surface modifiers.
Life Sciences, 1998
The efficient uptake of injected nanoparticles by cells of the mononuclear phagocyte system (MPS) limits the development of long-circulating colloidal drug carriers. The complement system plays a major role in the opsonization and recognition processes of foreign materials. Since heparin is an inhibitor of complement activation, nanoparticles bearing heparin covalently bound to poly(methy1 methacrylate) (PMMA) have been prepared and their interactions with complement evaluated. The particles retained the complement-inhibiting properties of soluble heparin. Nanoparticles bearing covalently bound dextran instead of heparin were weak activators of complement as compared with crosslinked dextran (Sephadexa) or bare PMMA nanoparticles. In addition to the specific activity of bound heparin, the protective effect of both polysaccharides is hypothesized to be due to the presence of a dense brush-like layer on the surface of the particles. Such properties are expected to reduce the uptake by MPS in vivo.