Physicochemical Characterization, Quantitative Drug Analysis, and Stability Testing of Hydroxytyrosol-loaded Poly(ԑ-caprolactone) Nanocapsules

Abstract

Hydroxytyrosol (HT) is a natural phenolic compound found in leaves of olive trees. It is a photosensitive solid phytochemical constituent and an irritant substance to skin and mucosa as pure drug. HT is a lipophilic chemical constituent and shows low solubility in water, bitter taste, and instability to oxidizing atmosphere. Considering the limitations for its suitable therapeutic use, the aim of the present study was to obtain, to characterize, to quantify, and to evaluate the stability of HT-loaded poly(ԑ-caprolactone) nanocapsules for its further use in pharmaceutical and nutraceutical products. Nanocapsules were prepared by method of interfacial deposition of the preformed polymer. The formulations were characterized by morphological and spectroscopic methods. The UHPLC-PDA analytical method was developed and validated for quantifying the HT encapsulation. Physicochemical stability assay was performed for 120 days. Nanocapsules were successfully obtained by the proposed method. The morphological evaluation demonstrated the drug absence in the nanocapsule surface. Fourier-transform infrared spectroscopy demonstrated the drug nanoencapsulation. The analytical method was validated and confirmed a high HT encapsulation efficiency over 95%. Considering the physicochemical stability testing, the polydispersity index changed after 30 days for NC-2 (HT at 2 mg/mL) and after 90 days for NC-5 (HT at 5 mg/mL). Zeta potential changed after 60 days for both formulations (NC-2 and NC-5). pH values were modified after 60 days for NC-5 and after 90 days for NC-2. HT-loaded PCL nanocapsules demonstrate adequate physicochemical features and high drug encapsulation. The different formulations revealed stability changes from 30 to 90 days. Additional in vitro and in vivo evaluations may be performed in order to use these nanoformulations for treating several diseases based on oxidative-inflammatory environments.

Keywords:
antioxidant; nanotechnology; Olea europaea; oleuropein; polyphenol.

HIGHLIGHTS

• Hydroxytyrosol (HT)-loaded PCL nanocapsules were appropriately obtained and characterized.

• A simple and fast UHPLC method for HT determination in PLC nanocapsules was developed and validated.

• High HT encapsulation efficiency was achieved into the PCL nanocapsule formulations.

• HT-loaded PCL nanocapsules showed physicochemical stability from 30 to 90 days.