Improved metabolic stability and therapeutic efficacy of a novel molecular gemcitabine phospholipid complex.
The aim of the present research is to increase lipid solubility, metabolic stability and therapeutic efficacy of water soluble gemcitabine (GEM) via phospholipid complex (PC) formation. A novel phospholipid complex of GEM was successfully prepared and optimized. Physical interaction of GEM with phospholipid was evaluated by DSC, FT-IR, 1H NMR, 31P-NMR and P-XRD. SEM images of GEM-PC showed rough structure and TEM images of diluted aqueous dispersion of GEM-PC showed micellar structure. In silico study also revealed the significant interaction between drug and phospholipid. GEM-PC demonstrated sustained drug release pattern and high plasma stability (∼2.2 fold) in vitro as compared to GEM. Increased in vitro cytotoxicity and apoptosis were observed with GEM-PC, when incubated with human pancreas adenocarcinoma cell lines. In vivo pharmacokinetics showed the almost 2 fold increase in AUC0-∞ (area under curve) with phospholipid complex (8983.26ngh/ml) as compared with GEM (4371.18ngh/ml) and GEMITA (4689.29ngh/ml). Toxicity studies signify the safety of GEM-PC over GEMITA. Pharmacodynamics studies in pancreatic tumor model further revealed higher efficacy of GEM-PC than GEMITA. These findings suggested the higher potential of phospholipid based technology for the enhancement of metabolic stability and therapeutic efficacy of GEM.
['Dora|Chander Parkash|CP|', 'Kushwah|Varun|V|', 'Katiyar|Sameer S|SS|', 'Kumar|Pradeep|P|', 'Pillay|Viness|V|', 'Suresh|Sarasija|S|', 'Jain|Sanyog|S|']
D000230:Adenocarcinoma D000818:Animals D045744:Cell Line, Tumor D003841:Deoxycytidine D065546:Drug Liberation D004355:Drug Stability D006801:Humans D008297:Male D051379:Mice D010190:Pancreatic Neoplasms D010743:Phospholipids D017207:Rats, Sprague-Dawley D017550:Spectroscopy, Fourier Transform Infrared D018675:Toxicity Tests
Stability Gemcitabine Phospholipid complex Lipid solubility Pancreas adenocarcinoma Anticancer