Design, optimization, and evaluation of methotrexate loaded and albumin coated polymeric nanoparticles

J Biomater Sci Polym Ed. 2024 Sep;35(13):2068-2089. doi: 10.1080/09205063.2024.2366619. Epub 2024 Jun 18.

Abstract

Methotrexate is a potent anticancer drug whose strong efflux is facilitated by the brain's efflux transporter. As an efflux transporter blocker, albumin increased the drug's concentration in the brain. Methotrexate-loaded nanoparticles were produced by evaporating the emulsification fluid. Improvements and analyses were made to the following aspects of the generated nanoparticles: size, polydispersity, zeta potential, entrapment efficiency, percentage yield, scanning electron microscopy, in vitro drug release studies, and sterilization. The particle size was determined to be in the nano range, and homogeneity of particle size was suggested by a low polydispersity index result. Particle diameters of 168 nm were observed in the F5 preparation, and zeta potential values of -1.5 mV suggested that the preparation produced adequate repulsive interactions between the nanoparticles. Albumin and dopamine HCl were employed to coat the methotrexate-loaded nanoparticles to guarantee that the brain received an adequate amount of them. The homogeneity of albumin coated nanoparticles was demonstrated by the low% PDI values of 0.129 and 0.122 for albumin coated nanoparticles (MNPs-Alb) and polymerized dopamine HCl and albumin coated nanoparticles (MNPs-PMD-Alb), respectively. After 48 h of incubation, the cell viability measured at the same drug concentration (5 mg) decreased for the F5, albumin coated nanoparticles, polymerized dopamine HCl coated nanoparticles, and polymerized dopamine HCl and albumin coated nanoparticles, respectively. Our primary findings demonstrate that the albumin nanoparticles containing methotrexate are designed to deliver the drug gradually. With minimal cytotoxicity, the intended preparation might give the brain an appropriate dosage of methotrexate.

Keywords: Methotrexate; PLGA; albumin; cancer; dopamine HCL; nanoparticles.

MeSH terms

  • Albumins / chemistry
  • Animals
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / chemistry
  • Antimetabolites, Antineoplastic / pharmacology
  • Cell Survival* / drug effects
  • Dopamine / chemistry
  • Drug Carriers* / chemistry
  • Drug Design
  • Drug Liberation*
  • Humans
  • Methotrexate* / administration & dosage
  • Methotrexate* / chemistry
  • Methotrexate* / pharmacokinetics
  • Methotrexate* / pharmacology
  • Nanoparticles* / chemistry
  • Particle Size*
  • Polymers / chemistry

Substances

  • Methotrexate
  • Drug Carriers
  • Dopamine
  • Albumins
  • Antimetabolites, Antineoplastic
  • Polymers