Title:Development of PEG-PLGA based Intravenous Low Molecular Weight Heparin (LMWH) Nanoparticles Intended to Treat Venous Thrombosis
VOLUME: 13 ISSUE: 5
Author(s):Satheesh Jogala, Shyam Sunder Rachamalla and Jithan Aukunuru
Affiliation:Gyana Jyothi College of Pharmacy, Boduppal, Hyderabad, Telangana 500098, India.
Keywords:Antithrombotic activity, aPTT, intravenous, low molecular weight heparin, macrophage uptake, nanoparticles, stability,
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.
Conclusion: An effective stealth LMWH nanoparticle formulation to treat venous thrombosis was successfully developed
using w/o/w solvent evaporation technique.
