title: Development of PEG-PLGA based Intravenous Low Molecular Weight Heparin (LMWH) Nanoparticles Intended to Treat Venous Thrombosis.
abstract: BACKGROUND
  Anticoagulant therapy is effective in the treatment of DVT. In this regard, LMWH demonstrated significant promise. It is widely used clinically. The goal of this study was to prepare and evaluate intravenous sustained release stealth nanoparticles encapsulating LMWH using PLGA (polylactidecoglycolide) and different grades of PEG (poly ethylene glycols).
  
  
  METHODS
  The nanoparticles were prepared using w/o/w solvent evaporation technique. Prepared nanoparticles were evaluated for particle size, encapsulation efficiency, in-vitro drug release, anti-thrombotic activity in venous thrombosis rat model, estimation of aPTT, tissue bio-distribution studies and stability.
  
  
  RESULTS
  Scanning electron microscopy (SEM) and Transmission electron microscopy (TEM) studies confirmed the formation of smooth spherical particles. FTIR study reveals successful coating of PEG on the nanoparticles. DSC and XRD results demonstrated that drug changed its physical form in the formulation. The encapsulation efficiency was 63-74%. In vitro drug release was 57-75% for 48 hrs. Macrophage uptake of LMWH with pegylated nanoparticles was less compared to conventional PLGA nanoparticles. In vivo drug release was sustained for 48hrs; Optimized formulation exhibited good enhancement in pharmacokinetic parameters when compared to free drug solution. In vivo sustained release was also demonstrated with antithrombotic activity as well aPTT activity. Optimized formulation demonstrated significant stability, excellent antithrombotic activity in venous thrombosis rat model, improved aPTT levels when compared to free drug solution.
  
  
  CONCLUSIONS
  An effective stealth LMWH nanoparticle formulation to treat venous thrombosis was successfully developed using w/o/w solvent evaporation technique.
authors.forename: Satheesh
authors.initials: S
authors.lastname: Jogala
authors.forename: Shyam Sunder
authors.initials: SS
authors.lastname: Rachamalla
authors.affiliation: Gyana Jyothi College of Pharmacy, Boduppal, Hyderabad, Telangana 500098, India. aukunjv@gmail.com.
authors.forename: Jithan
authors.initials: J
authors.lastname: Aukunuru
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001777:Blood Coagulation / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D036103:Nanotechnology; D010314:Partial Thromboplastin Time; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D017208:Rats, Wistar; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D014018:Tissue Distribution; D020246:Venous Thrombosis / Q000097:blood / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006495:Heparin, Low-Molecular-Weight; D011091:Polyesters; C000589473:polyethylene glycol-poly(lactide-co-glycolide); D011092:Polyethylene Glycols