Bioconjugates of PAMAM dendrimers with trans-retinal, pyridoxal, and pyridoxal phosphate

BACKGROUND: Bioconjugates of a polyamidoamine (PAMAM) G3 dendrimer and an aldehyde were synthesized as carriers for vitamins A and B(6), and the bioavailability of these vitamins for skin nutrition was investigated. METHODS: Nuclear magnetic resonance (NMR) and ultraviolet-visible methods were used to characterize the structure of the bioconjugates and for monitoring release of pyridoxal (Pyr) and pyridoxal phosphate (PLP) from these bioconjugates in vitro. A skin model permeation of bioconjugates was also studied in a Franz chamber. RESULTS: A transdermal G3 PAMAM dendrimer was used to synthesize bioconjugates with trans-retinal (Ret), pyridoxal (Pyr), or PLP. These nanomolecules, containing up to four covalently linked Ret, Pyr, or PLP (G3(4Ret), G3(4Pyr), and G3(4PLP)), were able to permeate the skin, as demonstrated in vitro using a model skin membrane. PLP and Pyr bound to a macromolecular vehicle were active cofactors for glutamic pyruvic transaminase, as shown by (1)H NMR spectral monitoring of the progress of the L-alanine + α-ketoglutarate → glutamic acid + pyruvic acid reaction. CONCLUSION: PAMAM-PLP, PAMAM-Pyr, and PAMAM-Ret bioconjugates are able to permeate the skin. PLP and Pyr are available as cofactors for glutamic pyruvic transaminase.