RESUMEN
5-Fluorouracil (5-FU) is one of the most potent drugs against solid tumors. However, its parenteral administration is associated with systemic toxicity, while its topical application has limited percutaneous absorption. To overcome these limitations, the current study undertakes the formulation of 5-FU as niosomal vesicles that were coated with hyaluronic acid to improve its targeting efficiency for cancer cells. The niosomes were prepared by the thin-film hydration method using cholesterol as physiological lipid and nonionic surfactants (Tween 80 and Span 80) in the ratio of 1:1. The niosomal vesicles were characterized for their size, size distribution, viscosity, surface tension, density, and drug entrapment efficiency. The vesicles were within the particle size range of 337-478 nm with relatively homogeneous particle size distribution (PDI ≤ 0.5). The ζ-potential and drug entrapment efficiency of coated formulations (F2 and F4) were comparatively higher than corresponding noncoated formulations (F1 and F3). The release behavior of 5-FU from niosomal vesicles using a dialysis membrane depicts that initial burst drug release was higher for F1 and F3 due to their smaller particle size in comparison to their coated counterparts. However, the release was more controlled for F4 due to the larger particle size, higher viscosity, and entrapped fraction of the formulation. The permeation of the drug through the rat's skin was comparatively higher in the case of noncoated formulations than their coated counterparts (p ≤ 0.05). This could be attributed to their small particle size and lower surface tension. In the case of coated formulations, the hydrophilic hyaluronic acid hinders the permeation of the drug through the lipid bilayer membrane of the skin. The retention of the drug in the skin was found to be in the range of 20-40%, which is sufficient to achieve optimum drug concentration in the tumorous tissue. Overall, the study successfully designed novel niosomal carrier systems for improved 5-FU delivery after topical application.
RESUMEN
Transdermal delivery is a potential alternative route to oral administration for drugs associated with stomach discomfort, such as flurbiprofen, a widely nonsteroidal anti-inflammatory drug (NSAID). This study aimed to design solid lipid nanoparticle (SLN) transdermal formulations of flurbiprofen. Chitosan-coated SLNs were prepared by the solvent emulsification method, and their properties and permeation profiles across the excised rat skin were characterized. The particle size of uncoated SLNs was at 695 ± 4.65 nm, which increased to 714 ± 6.13, 847 ± 5.38, and 900 ± 8.65 nm upon coating with 0.05, 0.10, and 0.20% of chitosan, respectively. The drug association efficiency was improved when a higher concentration of chitosan was employed over SLN droplets that endowed a higher affinity of flurbiprofen with chitosan. The drug release was significantly retarded as compared to the uncoated entities and followed non-Fickian anomalous diffusion that was depicted by "n" values of >0.5 and <1. Also, the total permeation of chitosan-coated SLNs (F7-F9) was significantly higher than that of the noncoated formulation (F5). Overall, this study has successfully designed a suitable carrier system of chitosan-coated SLNs that provide insight into the current conventional therapeutic approaches and suggest new directions for the advancements in transdermal drug delivery systems for improved permeation of flurbiprofen.