Investigation of Gentamicin Release from Polydopamine Nanoparticles

Abstract

Polydopamine (PDA), being highly reactive in nature, has acquired great attention in multi-disciplinary fields. Owing to its fascinating properties, including its biocompatible, non-toxic and readily bio-degradative nature, we investigated the drug loading and release behavior, using an aminoglycoside antibiotic gentamicin (G) as a model drug. The gentamicin was loaded into the PDA nanoparticles (NPs) via an in situ polymerization method. The release kinetics of the gentamicin was then studied in pH 3, 5 and 7.4. Two batches with varied gentamicin loadings, G-PDA NPs 1:1 (with approx. 84.1% loaded gentamicin) and G-PDA NPs 0.6:1 (with approx. 72.7% loaded gentamicin), were studied. The drug release data were analyzed by LC–MS. The PDA showed good stability in terms of gentamicin release at alkaline pH over a period of seven days. The negative surface charge of PDA at pH 7.4 makes a strong bond with gentamicin, hence preventing its release from the PDA NPs. However, at pH 5 and 3, the amine groups of PDA are more prone towards protonation, making PDA positively charged, hence the repulsive forces caused the gentamicin to detach and release from the G-PDA NPs. Consequently, approx. 40% and 55% drug release were observed at pH 5 and 3, respectively, from the G-PDA NPs 1:1. However, the drug released from G-PDA NPs 0.6:1 was found to be one half as compared to the G-PDA NPs 1:1, which is obvious to the concentration gradient. These findings suggested that the in situ loading method for gentamicin could provide drug release over a period of seven days, hence defending the drug’s efficacy and safety challenges. Furthermore, two kinetic models, namely the Ritger–Peppas and Higuchi models, were implemented to determine the drug release kinetics. Curve fitting analysis supported our findings for the drug release kinetics which are followed by PDA structural changes in response to pH.