Several novel, innovative approaches for improving transdermal delivery of BCS class III drugs have been proposed. Despite their great aqueous solubility, BCS class III drugs have the drawback of limited permeability. The objective of the current work was to screen the suitability of niosomes as a nanocarrier in permeation enhancement of azithromycin (AZM) transdermal delivery. Niosomes were prepared by an ether injection method using a nonionic surfactant (Span 60) and cholesterol at different concentrations. The ζ potential (ZP), polydispersity index (PDI), and particle size (PS) of AZM-loaded niosomes were evaluated. The size of the niosomes was found to vary between 288 and 394 nm. The results revealed that the niosomes prepared in a ratio of 2:1 (Span 60: cholesterol) had larger vesicle sizes, but all of them were characterized by narrow size distributions (PDI <0.95). Niosomal gel was successfully prepared using different polymers. The appearance, pH, viscosity, and ex vivo drug release of niosomal gel formulations were all examined. The flow curves showed that the niosomal gel displayed lower viscosity values than its corresponding conventional gels. Niosomal and conventional gels exhibited a domination of the elastic modulus (G′) over the viscous modulus (G″) (G’>G″) in the investigated frequency range (0.1–100 rad/s), indicating stable gels with more solid-like properties. Ex vivo skin permeation studies for the niosomal gel show 90.83 ± 3.19% of drug release in 24 h as compared with the conventional gel showing significantly lower (P < 0.001) drug release in the same duration (1.25 ± 0.12%). Overall, these results indicate that niosomal gel could be an effective transdermal nanocarrier for enhancing the permeability of AZM, a BCS class III drug. In conclusion, this study suggests that transdermal formulations of AZM in the niosomal gel were successfully developed and could be used as an alternative route of administration.

The subgingival application of the formulated 2% mucoadhesive GSE gel showed significant improvement in the PI and GI only.