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Aim: The study aimed to formulate solid lipid nanoparticles (SLNs) for the transdermal delivery of PPL to improve skin retention and efficacy., Materials and Method: The particle size distribution of SLNs was determined and the morphology of SLNs was also analyzed by SEM. In-vitro , ex-vivo and in vivo evaluations were done for PPL loaded SLN. The safety of drug delivery systems was assayed using MTT test., Results: The results indicated successful encapsulation of PPL in SLNs (59.38%), which exhibited a spherical shape and smooth surface. Compared to PPL solution, SLNs demonstrated a prolonged drug release profile in vitro . Stability tests over three months showed no significant changes in entrapment efficiency or size distribution. Enhanced permeation through shed snake and rat skin was observed with SLNs compared to the PPL solution. Ex-vivo and in vivo studies confirmed that PPL-loaded SLNs significantly increased drug content in the skin. Importantly, the SLNs displayed biocompatibility, as no significant cytotoxic effects were noted, and they were nonirritating to rat skin., Conclusion: To the best of our knowledge, this is the first study that indicates SLNs can be considered as a promising nanocarriers for transdermal delivery of PPL.