Propolis-based niosomes as oromuco-adhesive films: A randomized clinical trial of a therapeutic drug delivery platform for the treatment of oral recurrent aphthous ulcers

Abstract

Oromuco-adhesive films for buccal delivery of Propolis extract (PPE) entrapped in niosomes, were prepared to treat oral recurrent aphthous ulcer (RAU). PPE was investigated for antimicrobial compounds. Niosomes composed of span60 and cholesterol were evaluated for particles size, polydispersity index (PDI), zeta-potential, entrapment efficiency and in vitro release. The formed oromuco-adhesive films containing niosomal PPE were evaluated for swelling, mucoadhesion and elasticity. 24 patients suffering from RAU were divided equally into medicated and placebo groups and participated in this study to examine the onset of ulcer size reduction, complete healing and pain relief. Ultra-performance liquid chromatography-high resolution mass spectrometry revealed the presence of pinocembrin, pinobanksin, chrysin and galangin as antimicrobial flavonoids with total content of 158.7 ± 0.15 µg quercetin equivalents and phenolic content of 180.8 ± 0.11 µg gallic acid equivalents/mg. Multilamellar niosomes of 176–333 nm displayed entrapment efficiency of 91 ± 0.48%, PDI of 0.676 and zeta potential of −4.99. In vitro release after 8 h from niosomal dispersion and films were 64.05% and 29.09 ± 0.13% respectively. Clinical results revealed duration of film adherence from 2–4 h in the two groups. The onset of ulcer size reduction in medicated group was attained within second and third day, complete healing was achieved within first 10 days of treatment and pain relief lasted for more than 4–5 h, in contrast to the placebo group. This oromuco-adhesive films which offer controlled and targeting drug delivery can be proposed as a new therapeutic strategy in the treatment of oral recurrent aphthous ulcer.

Multi Dynamic Extraction: An Innovative Method to Obtain a Standardized Chemically and Biologically Reproducible Polyphenol Extract from Poplar-Type Propolis to Be Used for Its Anti-Infective Properties

“…Propolis polyphenols, although beneficially bioactive molecules, pose problems of low bioavailability, and thus may benefit from targeted nanodelivery systems via nanocarriers [56]. In particular, permeation through the buccal mucosa appears to be a promising approach to bypass liver metabolism and release propolis-based nano-formulations and niosomes locally or systemically [57,58].…”

Optimization and evaluation of propolis liposomes as a promising therapeutic approach for COVID-19

“…This could be attributed to increased width of lipid bilayer membrane. Interestingly, Arafa et al ( Arafa et al, 2018 ) stated the increased E.E% of propolis with increased DL which could be attributed to the enhanced capacity of the prepared nanostructure. Unlikely, Results showed that CH% had no effect on E.E % of the prepared PP-Lip.…”

Niosome-Based Approach for In Situ Gene Delivery to Retina and Brain Cortex as Immune-Privileged Tissues

“…An interesting approach to enhance the physical stability of niosomes is to obtain a stable dry powder formulation by lyophilization that can later be resuspended in the appropriate solvent before use. In this case, the selection and the concentration of the cryoprotector, along with the parameters of the lyophilization process need to be evaluated to guarantee the stability of the dry powder [107,108]. The analysis of some of the previously described physicochemical parameters on a niosome formulation can be observed in Figure 4.…”