Author : Črt Dragar
Publisher :
Page : 128 pages
File Size : 12,53 MB
Release : 2019
Category :
ISBN :
Poly(lactic-co-glycolic) acid nanoparticles have gained enormous interest in the recent 40 years for their use in pharmaceutics, diagnostics and theranostics. They show numerous advantages, such as biodegradability and biocompatibility, ability to deliver different types of drugs, surface properties, which enable further modifications and possibility of controlled drug release. Nonetheless, poly(lactic-co-glycolic) acid nanoparticles still have some drawbacks, which hinder their transition from research into clinical practice. The aim of this study was to establish and implement protocols for preparation of poly(lactic-co-glycolic) nanoparticles for application in drug delivery. Non-functionalized (i.e., uncoated) as well as chitosan- and poly(ethylene imine) functionalized (i.e., coated) nanoparticles were prepared and characterized with regard to their particle size and particle size distribution, zeta potential, surface hydrophobicity/ hydrophilicity, morphology, solid state properties, and cellular interactions using buccal human TR 146 cells. The rheological properties of poly(lactic-co-glycolic) acid nanoparticles dispersions were also determined. Moreover, selected formulations were freeze-dried and stability studies were conducted for two months. Poly(lactic-co-glycolic) acid nanoparticles were prepared based on emulsion-diffusion-evaporation method. Stirring rates, homogenization set up and stabilizer concentration were adjusted to achieve reproducible preparation of nanoparticle formulations. Hydrodinamic particle size ranged from 230 nm to 330 nm. Chitosan-coated nanoparticles had zeta potential of ~+30 mV, poly(ethylene imine)-coated particles showed values of ~+10 mV and uncoated nanoparticles revealed a zeta potential of ~- 5 mV. All formulations showed the polydispersity index smaller than 0.25. Freeze-drying of uncoated and poly(ethylene imine)-coated nanoparticles was successful without the use of additional lyo- and/or cryo-protectants. The freeze-dried formulations were stable at 2-8 °C for at least two months. The uncoated nanoparticles showed the highest hydrophobicity, followed by the poly(ethylene imine)- and chitosan-coated ones. The positively charged nanoparticles interacted with the cell membrane, whereas the negatively charged nanoparticles were internalized by the cells in vitro. To sum up, robust protocols were successfully established that enabled the reproducible preparation of uncoated and chitosan-coated poly(lactic-co-glycolic) acid nanoparticles. However, the protocol for preparation of poly(ethylene imine)-coated poly(lactic-co-glycolic) acid nanoparticles was shown to be inefficient and should be further optimized in the future studies.