Synthesis of gold nanoparticles with amphiphilic pullulan derivatives/folic acid for cancer drug transdermal delivery

Abstract

Pullulan-stabilized gold nanoparticles (AuNPs) have been used extensively in the transdermal delivery system; however, the weakness is the low penetrability through the skin which decreased intracellular amount of active pharmaceutical ingredient (API). This research focused on the surface modification of AuNPs using amphiphilic pullulan derivatives/Folic acid (AuNPs@AmPQ188-FA) for enhance the efficiency of drug delivery through skin and used 5-fluorouracil (5-FU) as a drug model. Surface of AuNPs was functionalized with 3 compartments as followed: (1) quat188 (Q188) which provides a positive charge for enhancing cellular uptake, (2) stearic acid (C18), a hydrophobic component, for improving the penetrability and intracellular transferal properties of hydrophobic drugs, (3) folic acid (FA) as a targeting ligand to bind with folate receptor on cancerous cell membranes and enhance intracellular uptake. Synthesis of AuNPs@AmPQ188-FA were characterized by UV-Vis spectrophotometer and DLS an average size of 135.47 ± 3.48 nm and zeta potential of 26.30 ± 4.17 mV. The 5-Fu loaded on AuNPs@AmPQ188-FA (5-Fu AuNPs@AmPQ188-FA) at pH 9.0 and ratio of 5-Fu : AuNPs@AmPQ188-FA was 0.5:1 at room temperature. 5-Fu entrapment efficiency was 68.28 ± 0.33%. In vitro drug penetration was investigated by Franz’s diffusion cell method. The 5-Fu AuNPs@AmPQ188-FA penetration was investigates by UV-Vis spectrophotometer that shown increasing penetration to across cellulose membrane. According to the results, it was suggested that The 5-Fu AuNPs@AmPQ188-FA can be a good candidate to further development for transdermal delivery applications.