Background: Topical drug administration offers an attractive route with minimal invasiveness. It also
avoids limitations of intravenous administration such as the first pass metabolism and presystemic elimination
within the gastrointestinal tract. Furthermore, topical drug administration is safe, have few side effects, is easy to
apply, and offers a fast onset of action. However, the development of effective topical formulations still represents
a challenge for the desired effect to be reached, locally or systemically. Solid lipid nanoparticles and nanostructured
lipid carriers are particular candidates to overcome the problem of topical drug administration. The
nanometric particle size of lipid nanoparticles favors the physical adhesion to the skin or mucosal, what can also
be attained with the formation of hybrid (nanoparticles/polymer) systems.
Methods: In this review, we discuss the major challenges for lipid nanoparticles formulations for topical application
to oral mucosa, skin, and eye, highlighting the strategies to improve the performance of lipid nanoparticles
for topical applications. Next, we critically analyzed the in vitro and in vivo approaches used to evaluate lipid
nanoparticles performance and toxicity.
Conclusion: We addressed some major drawbacks related to lipid nanoparticle topical formulations and concluded
the key points that have to be overcome to help them to reach the market in topical formulations to oral
mucosa, skin, and eye.