Impact of Cholesterol and Surfactant Selection on Tacrolimus-Loaded Niosomes for Transdermal Drug Delivery

Introduction: Tacrolimus, a potent immunosuppressant, faces several limitations in transdermal delivery due to its higher molecular weight, pressing the need to encapsulate in niosomes. Various formulations (F1 to F9) were prepared using different non-ionic surfactants (Span 40, Span 60, and Brij 98) and varying cholesterol concentrations. This study aimed to evaluate the influence of surfactant type on particle size, polydispersity index, encapsulation efficiency, and in-vitro drug release. Methods: A total of nine niosomal formulations were developed using varying ratios of drug, surfactant, and cholesterol to optimize vesicle characteristics and drug delivery performance. Three nonionic surfactants, Span 40, Span 60, and Brij 98, were employed due to their distinct hydrophiliclipophilic balance (HLB) and vesicle-forming abilities. The formulations were prepared by the thin film hydration method, in drug: surfactant: cholesterol ratios of 1:1:0.2, 1:1:0.4, 1:1:0.6, 1:1.5:0.3, 1:2:0.4, 1:1:0.5, 1:1:0.75, 1:1:1, and a repeat of 1:1:0.2. Each formulation was evaluated for vesicle size, zeta potential, polydispersity index (PDI), entrapment efficiency, and cumulative drug release over 24 hours. Vesicle size and PDI were measured using dynamic light scattering, while zeta potential was assessed to determine colloidal stability. Entrapment efficiency was calculated by separating the unencapsulated drug via centrifugation, and drug release was studied using a dialysis diffusion method. Results: Results indicated that niosomes formulated with Brij 98 exhibited significantly smaller particle size and demonstrated the highest encapsulation efficiency due to its higher hydrophilic-lipophilic balance (HLB) values than Span 40 and Span 60. Among all formulations tested, F8 (comprising Drug: Brij 98: cholesterol in a molar ratio of 1:1:0.75) showed optimal characteristics with a vesicle size of 293 ± 0.75 nm, zeta potential of -21.6 ± 0.20 mV, PDI of 0.148 ± 0.006, encapsulation efficiency of 78.36 ± 0.66 %, and 71.2 ± 1.97 % drug release over 24 hours. Discussion: The study demonstrates that surfactant type significantly influences the characteristics of Tacrolimus-loaded niosomes. Brij 98, due to its higher HLB and flexible chains, produced smaller vesicles with superior entrapment and stability. In contrast, Span 40 and Span 60 formed larger, less efficient vesicles. These findings underscore the importance of surfactant selection in optimizing niosomal drug delivery. Conclusion: In conclusion the successful fabrication of niosomes and the achievement of desired size and uniformity crucially depend on the composition of niosomes, particularly the type of surfactant employed.