In vitro and in vivo evaluation of Bola-surfactant containing niosomes for transdermal delivery

Abstract

A novel niosome formulation is proposed for topical drug delivery of ammonium glycyrrhizinate, a natural compound with an efficacious anti-inflammatory activity. Niosomes were made up of a new non ionic surfactant, alpha,omega-hexadecyl-bis-(1-aza-18-crown-6) (Bola-surfactant)-Span 80-cholesterol (2:3:1 molar ratio). Niosome vesicles were prepared with the thin layer evaporation method and were physico-chemically characterized. The tolerability of Bola-surfactant both as free molecules or assembled ion niosome vesicles was evaluated in vitro on cultured of human keratinocyte cells (NCTC2544). Human tolerability was evaluated on volunteers. The ability of Bola-niosomes to promote intracellular delivery was evaluated by confocal laser scanning microscopy (CLSM) studies. Human stratum corneum and epidermis (SCE) membranes were used in vitro to investigate the percutaneous permeation. The anti-inflammatory activity of ammonium glycyrrhizinate was evaluated in vivo on human volunteers with a chemically induced erythema. Experimental data show that Bola-niosomes are characterized by a mean size of approximately 400 nm and are able to provide an encapsulation efficiency of 40% with respect to the drug amount used during preparation. CLSM showed that Bola-niosomes were able to promote the intracellular uptake of the delivered substances. Bola-niosomes were also able to significantly improve (p<0.001) the percutaneous permeation of ammonium glycyrrhizinate with respect to both the aqueous drug solution and a physical mixture between unloaded Bola-niosomes and the aqueous drug solution. Bola-niosomes showed a suitable tolerability both in vitro and in vivo. Ammonium glycyrrhizinate-loaded Bola-niosomes determined a significant (p<0.001) and noticeable improvement of the in vivo anti-inflammatory activity of the drug. An effective example of conjugating innovative colloidal carriers, coming from pharmaceutical nanotechnology, and therapeutically effective natural compounds, coming from traditional medicine, was reported.

Ammonium glycyrrhizinate-loaded niosomes as a potential nanotherapeutic system for anti-inflammatory activity in murine models

“…53 AG was released from bola-surfactant NSVs within the first 3 hours, indicating zero-order release kinetics. The release profile of AG from bola-surfactant NSVs was also constant until 8 hours, indicating the kinetics of a colloidal reservoir system.…”

“…The lack of cytotoxicity seen for the empty vesicles may be attributable to the self-assembling of nonionic surfactants into colloidal structures, as has been reported previously. 32,53 Cytotoxicity to primary human dermal fibroblasts occurred using the same concentration of nonionic surfactants (1 µM) and by extending the incubation time over 24 hours. The data obtained demonstrate that cytotoxicity is time-dependent and is further increased at 72 hours of incubation (∼60% for empty NSVs and AG 1% w/v NSVs).…”

Niosomes: A Controlled and Novel Drug Delivery System

“…1,2) So, niosome or non-ionic surfactant vesicles are now widely studied as an alternative tool to liposome. Various types of surfactants have been reported to form vesicles, and have the capacity to entrap and retain the hydrophilic and hydrophobic solute particles.…”

Niosomes as Carrier in Dermal Drug Delivery

“…The drug associated toxicity were also reduced (Rogerson et al, 1987). Niosomes which have been prepared with Bola-surfactants showed a certain and encouraging safety and tolerability both in vitro on human keratinocyte cells up to an incubation time of 72 h for the different concentrations studied (0.01-10 µM) and in vivo on human volunteers t h a t s h o w e d n o s k i n e r y t h e m a w h e n topically treated with the drug free Bola-niosome formulation (Paolino et al, 2007).…”