Aminolevulinic Acid Hydrochloride

Aminolevulinic acid hydrochloride (ALA) suppresses angiotensin converting enzyme 2 (ACE2) expression in host cells, a key entry receptor for SARS-CoV-2. In vitro experiments demonstrated that ALA administration reduced ACE2 expression on the surface of cultured cells, which was associated with decreased intracellular porphyrin levels. Co-administration of ALA with sodium ferrous citrate (SFC) produced a further decrease in ACE2 expression and led to increased intracellular heme levels, suggesting that the suppressive effect on ACE2 occurs through heme biosynthesis pathway activation. Inhibition of heme oxygenase-1 (HO-1), an enzyme involved in heme degradation, also resulted in reduced ACE2 expression, indicating a potential role for HO-1 in mediating this suppression.

Fig. 1 The uptake of 5-Aminolevulinic acid and conversion of PpIX into heme. (Nara E.; et al. 2023)

5-Aminolevulinic acid hydrochloride was loaded into lecithin-based invasomes composed of egg lecithin, either DLaPC or DOaPC, and the terpene limonene for enhanced transdermal delivery in photodynamic therapy. The optimized invasomes exhibited a spherical morphology with an average size of 150 nm and encapsulation efficiency of 80 percent. Ex vivo epidermis diffusion tests demonstrated that terpene-containing nanovesicles achieved up to 80 percent skin penetration within 3 hours, compared to less than 50 percent for terpene-free vesicles and free ALA. In 2D and 3D human melanoma cell models, the invasomes enhanced intracellular ALA transport, increased ROS generation upon irradiation, and produced a significant antiproliferative effect.

Fig. 2 5-Aminolevulinic acid hydrochloride-loaded lecithin-based invasomes. (Gaballo A.; et al. 2023)