Preparation and physicochemical characterization of paramagnetic filgrastim (G-CSF) loaded nanoliposomes and investigation of effects on M-NFS-60 cell line

Abstract

Introduction: Granulocyte colony-stimulating factor (G-CSF) or filgrastim is a polypeptide growth factor that regulates the production of neutrophilic granulocytes. Recent studies have shown that release of the drugs using nano sized vehicles have different advantages such as increasing solubility, target therapy, increasing accumulation inside the cells, decreasing toxicity, decreasing frequency of administration and increasing maximum tolerable doses. Objectives: The purpose of this study was preparation and investigation of the physicochemical properties of filgrastim loaded optimized paramagnetic liposomes. Materials and Methods: Experimental design methods and multi factorial equations, graphical images and optimization of responses were employed to evaluate the effects of each formulation parameter in the responses and also prediction of optimized formulation for filgrastim liposomes. Filgrastim liposomes were prepared with Di Palmytoil Phosphatidil Cholin and Cholesterol using film hydration technique. Protein content was measured using HPLC and micro BCA protein assay. Cell proliferation studies were performed on NFS-60 cell lines using MTT method. Results: The particle sizes of the liposomes were in the range of 569 nm and 1119 nm. Encapsulation efficiency percentages were between 42.6% and 73.7% in the liposomes. The average of remained drug in the liposomes after 12 months of storage at 4°C was 95.3% of initial filgrastim content. Liposomal formulations released the protein around 60%-65% after 24 hours. Cell proliferation studies showed that the proliferative effects of liposomes and paramagnetic liposomes are the same as filgrastim solutions.

Conclusion: The results of this study showed that liposomal formulations and paramagnetic nanoliposomes of filgrastim could be used for controlling the drug release and consequently lowering the frequency of administration and also possible targeted drug delivery for treatment of chemotherapy induced neutropenia.