Ahmad Ainurofiq, Elena Putri Maharani, Inneke Nurul Dwi Putranti, Nayla Khanza Wijaya, Rossi Chelsita Azizah Rachma Putri, Vania Maharani, Md Takit Ahamed
Transdermal drug delivery provides a noninvasive alternative to oral administration, though its efficacy is limited by the stratum corneum barrier. Lipid-based drug delivery systems are increasingly used to address this challenge. This review evaluates the relationship between the physicochemical characteristics of lipid-based particles and their resulting transdermal permeability. A structured literature search of ScienceDirect, PubMed, and Google Scholar (2015-2025) was conducted to identify original research articles reporting quantitative in vivo and ex vivo skin permeability data. The study analyzed nanoemulsions, solid lipid nanoparticles and nanostructured lipid carriers (NLC) based on particle size, polydispersity index (PDI), and zeta potential. Smaller particle size (<150 nm), low PDI, and stable zeta potential (≥ |20| mV) were observed to correlate with increased flux and permeability coefficients. Among the systems reviewed, NLCs frequently demonstrated superior permeability characteristics attributed to a flexible matrix that enhances drug loading and interactions with skin lipids. Optimizing these physicochemical parameters appears essential for achieving superior permeability in lipid-based transdermal systems, offering potential benefits for clinical pharmacy practice and drug bioavailability.