Nanoparticulate fingolimod delivery system based on biodegradable poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV): design, optimization, characterization and in-vitro evaluation

Abstract

This study was focused on the fabrication, statistical optimization and in vitro characterization of poly (hydroxybutyrate-co-hydroxyvalerate) (PHBV) nanoparticles loaded with fingolimod. PHBV-based fingolimod nanoparticles were prepared by single and double evaporation methods; the incorporation efficiency of fingolimod was higher with the single emulsion evaporation method in the nanosize range particles. Fingolimod HCL was neutralized with NaOH in order to slow down the release of the highly soluble fingolimod. The encapsulation efficiency of neutralized fingolimod was much higher (53–73%) due to the insoluble form of the drug used in encapsulation. It was found that the amount of fingolimod, concentration of PHBV and polyvinyl alcohol (PVA) would influence the encapsulation efficiency significantly. The effect of these parameters on the Particle size, PdI, loading capacity and loading efficacy was studied. The optimum conditions were 1.32% PHBV, 0.42% PVA and 5 mg fingolimod. The average size of optimized nanoparticles which measured with the aid of the Box–Behnken experimental design was 250 nm and entrapment efficiency of 73(%). Drug-release from the nanospheres over a four-week period has shown a characteristic triphasic release pattern with an initial burst effect.

Keywords:

• Biodegradable
• box-Benkehn design
• drug delivery
• fingolimod
• poly (3-hydroxybutyrate-co-hydroxyvalerate)

Declaration of interest

This work has been supported by a research (grant NO: 21609) awarded by Tehran University of Medical Sciences. The authors report no conflict of interest.