Novel biosurfactant and lipid core-shell type nanocapsular sustained release system for intravenous application of methotrexate.
In an attempt to prepare novel core shell nanocapsules, lipid and Stearic acid-Valine conjugate (Biosurfactant) based nanosystem was prepared to attain high drug loading of hydrophilic drug methotrexate (MTX), with sustained release. Antisolvent nanoprecipitation technique was employed for the formulation of nanoparticles (NPs). Optimized formulation depicted 209.6 ± 31.3 nm particle size, 0.209 ± 0.072 PDI and 14.98 ± 1.33 %w/w drug loading. In vitro release depicted biphasic release for 12 h with initial burst phase followed by sustained release phase. In vitro Haemolytic study on RBCs revealed haemocompatible nature of MTX-Biosurfactant NPs compared to Biotrexate® (Zydus). In vitro cell culture studies showed 3.33 folds and 3.50 folds increase in cellular uptake of MTX at 10 µg/ml and 15 µg/ml concentration respectively for developed nanoparticles with 4.16 folds decrease in IC50 value. Higher apoptosis and increased lysosomal membrane permeability were obtained in MTX-Biosurfactants NPs. AUC and T1/2 was found to increase by 2.55 and 3.25 folds respectively in pharmacokinetic study. Significant reduction in tumor burden and serum toxicity marker level depicted efficacy and safety respectively of the formulation as compared to Biotrexate®. RBCs morphology was retained after MTX-Biosurfactants NPs exposure proving its haemocompatibility in vivo.
['Katiyar|Sameer S|SS|', 'Kushwah|Varun|V|', 'Dora|Chander Parkash|CP|', 'Jain|Sanyog|S|']
D061605:Administration, Intravenous D000818:Animals D000970:Antineoplastic Agents D002470:Cell Survival D003692:Delayed-Action Preparations D065546:Drug Liberation D004912:Erythrocytes D005260:Female D006461:Hemolysis D006801:Humans D008055:Lipids D061986:MCF-7 Cells D008727:Methotrexate D051379:Mice D053758:Nanoparticles D009369:Neoplasms D017207:Rats, Sprague-Dawley D013501:Surface-Active Agents D047368:Tumor Burden D014633:Valine
Sustained release Methotrexate Core shell nanocapsule Reduced toxicity