Preparation, Characterization and In Vitro Evaluation of Metformin Loaded Hyaluronic Acid Nanoparticles for Oral Delivery
Abstract
Metformin, an anti-diabetic drug, has a low oral bioavailability (50-60%) due to its poor intestinal absorption. Orally administered mucoadhesive nanoparticles have been shown to interact with the intestinal mucus layer and increase the intestinal permeability of the entrapped drug. The objective of the present study was to develop and characterize polymeric nanoparticulate system containing metformin with a mucoadhesive polymer hyaluronic acid. Blank and drug loaded nanoparticles were prepared using hyaluronic acid polymer by precipitation method with a high entrapment efficiency. The average particle size of the blank and drug loaded nanoparticles was found to be 155.52 ±18.70 nm and 114.53 ± 12.01 nm, respectively. Atomic force microscopy (AFM) revealed that the nanostructures were in form of nanofibres. Zeta potential was found to be in the range of -0.27 to 0.24 mV. Physical stability studies indicated that the particle size was maintained at 50% of metformin was released within one hour. Metformin nanoparticles were non-toxic at a concentration of ≤ 100 µM in Cacco-2 cells. Haemolysis studies indicated that these nanoparticles can also be safely administered via intravenous route. Cellular uptake studies on Caco-2 cells indicated higher uptake of metformin from nanoparticle relative to that from metformin solution, up to first 45 minutes. Permeability studies indicated no passive permeation of the nanoparticles through a synthetic membrane lacking mucin. Thus requires…
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