Human plasma-derived exosomal gel: a biomimetic cargo for the transdermal delivery of methotrexate

The aim of the study was to explore the potential of human plasma-derived exosomal gel as a carrier for transdermal drug delivery. Exosomes were isolated from human plasma through a combination of ultracentrifugation and dialysis techniques. Methotrexate (MTX), a weak acid drug with log P 1.53 (low permeability), was utilised as a model drug. MTX was loaded into exosomes using the freeze-thaw method. MTX-loaded exosomes were incorporated into a gel, employing carbopol 940 as a gelling agent. MTX loaded exosomes exhibited a mean size of 162.15 ± 4.21 nm, a polydispersity index (PDI) 0.372 ± 0.024, and a zeta potential of -30.6 ± 0.71 mV. Exosomal gel displayed good physicochemical properties along with desirable rheological behaviour that eased skin application. MTX-loaded exosomal gel exhibited sustained release of 59.14 ± 0.812% of the drug within 72 h at pH 7.4 as compared to nonexosomal gel <i>p</i> < 0.0001. MTX-loaded exosomal gel demonstrated a three-fold increase in skin permeability as compared to MTX loaded gel. Moreover, results of <i>in-vivo</i> studies on the carrageenan-induced inflammation model indicated exosomal gel and MTX loaded exosomal gel reduced inflammation as compared to MTX gel. These findings suggested the potential of exosomes as an emerging platform for transdermal drug delivery, offering enhanced skin penetration.